Grants and Awards

One-year period ending October 1, 2018. Click on a title to read more.
Awards information as defined in UW SAGE.
Mechanisms of regulation of retinoic acid homeostasis.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 09/13/2018
Sponsor: National Institutes of Health (NIH) Amount: $413423
Abstract
Obesity is a major public health problem with 38% of American adults being obese and rates of obesity increasing dramatically worldwide. It is estimated that obesity is second only to smoking as a cause of premature preventable death. This is largely due to the comorbidities associated with obesity including metabolic syndrome, diabetes, cardiovascular disease and nonalcoholic fatty liver disease. Yet, very little progress has been made in the development of treatments to prevent obesity and its comorbidities, and the mechanistic link between obesity and development of comorbidities is not completely understood. Several studies have shown that obese rodents develop tissue vitamin A deficiency, with tissue retinoid concentrations decreasing by a stunning 75-90%, suggesting profound metabolic dysregulation. Findings in cell systems and animal models demonstrate that retinoids regulate adipocyte differentiation and glucose and lipid metabolism and, further, that decreased retinoid concentrations are associated with progressive obesity, insulin resistance and glucose intolerance. Thus, aggregate preclinical data suggest that altered vitamin A metabolism may contribute directly to obesity progression and the development of obesity-related co-morbidities. Critically, the mechanisms underlying this dysregulated vitamin A metabolism remain poorly understood, and the relevance of these preclinical findings to human obesity is unclear. A central premise of this proposal is that altered vitamin A metabolism in obesity is a result of increased inflammatory cytokines (IL-1?, IL-6 and TNF?? in metabolic tissues, which regulate the expression of the retinoid metabolizing enzymes CYP26, LRAT, ALDH1A and RDH in adipocytes and various liver cell types. We further hypothesize that this dysregulation of vitamin A metabolism occurs in human obesity as well as in animal models. We will test our hypotheses in two specific aims: 1) to identify the enzymes and the key regulatory signals that control all-trans-retinoic acid (atRA) concentrations and vitamin A metabolic flux in human liver and adipose tissue, and 2) to establish whether adipose tissue and liver vitamin A metabolomes are altered in obese humans. We will use our state-of-the-art mass spectrometry methods, innovative metabolic flux experiments and kinetic modeling in specific cell types to characterize the key enzymes that metabolize retinoids in liver and adipose tissue and determine how the activity of these enzymes is altered in obesity. To determine whether tissue retinoids are altered in human obesity, we will conduct a cross sectional clinical study comparing visceral and subcutaneous adipose tissue, liver and serum vitamin A metabolomes in obese and non-obese subjects. The proposed studies will lay the foundation for understanding the regulation of vitamin A metabolism in human liver and adipose tissue and for determing how vitamin A metabolism may become dysregulated in obesity contributing to progressive obesity and its co-morbidities in humans. The results will generate unprecedented insight into human retinoid biology and ultimately could lead to targeted therapeutic interventions designed to restore tissue retinoid signaling as a novel strategy for the treatment of obesity and its sequela.
Personnel
Isoherranen, Nina, Principal Investigator, Professor, PHARMACEUTICS • Zhong, Guo, Other, Senior Fellow, PHARMACEUTICS • LAFRANCE, JEFFREY M, Other, Student Assistant (NE H), PHARMACEUTICS • Crispe, Ian N., Co-Investigator, Professor without Tenure, PATHOLOGY • Rubinow, Katya B., Multiple PI, Assistant Professor without Tenure, DEPARTMENT OF MEDICINE • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Diamond, Deborah L, eGC1 Preparer, RESEARCH MANAGER, PCEUT - ADMIN, PHARMACEUTICS
Screening of Investigational Compounds to Treat, Modify or Prevent Epilepsy for the NINDS Epilepsy Therapy Screening Program (ETSP).
WHITE, HAROLD STEVE , Department Of Pharmacy
Award Date: 09/06/2018
Sponsor: University of Utah Amount: $27780
Abstract
The systemic kainic acid (KA)-induced status epilepticus (SE) model in rats is an etiologically-relevant animal model of epileptogenesis. All of the clinical characteristics observed in human patients with temporal lobe epilepsy (TLE) are also observed in the rat systemic KA model of SE and TLE. Moreover, the systemic low-dose KA paradigm is ideally suited for preclinical drug screening studies to evaluate the long-term process of epileptogenesis. As a first attempt to identify novel and potentially efficacious antiepileptogenic agents, it is necessary to define whether administration of the investigational compound during the SE insult or immediately after (e.g. during the latent period) can first modify presentation and severity of spontaneous recurrent seizures, as well as attendant comorbidities, in the rat KA-SE model of epileptogenesis. The goal of the proposed studies is to determine whether administration of promising investigational anticonvulsant compounds can also modify or attenuate the presentation of spontaneous recurrent seizures days to weeks after SE, as well as modify the SE-induced behavioral deficits associated with TLE.
Personnel
White, Harold Steve, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Haliski, Melissa, Key Personnel, Research Scientist/engineer-senior, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY , Dept Of Pharmacy, Budget Preparer
Equipment Supplement for The plasma membrane monoamine transporter (PMAT): expression and role in mIBG disposition in neuroblastoma.
WANG, JOANNE , Pharmaceutics
Award Date: 09/04/2018
Sponsor: National Institute of General Medical Sciences (NIGMS) Amount: $111409
Abstract
BZ-X710 all-in-one fluorescence microscope: $111,409 is requested for the purchase of this equipment per attached quote from Keyence Corporation of America. This instrument purchase qualifies for tax exempt. Keyence Corporation of America is the only source that can provide the desired equipment, software, and support. There are no other digital all-in-one systems available that include a high sensitivity CCD camera, built-in dark room, automatic stage, automatic lenses, automatic filters, live cell incubation/video/time lapse image capture, fluorescence, phase contrast, and bright field observation modes. The compact size also maximizes lab space. The Keyence BZ-X710 will add much needed capabilities to this lab and will become an essential equipment to support studies proposed in the parent R01 project.
Personnel
Wang, Joanne, Principal Investigator, Professor, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Empowering the Annual Health Econometrics Workshop.
BASU, ANIRBAN , Department Of Pharmacy
Award Date: 09/04/2018
Sponsor: Agency for Healthcare Research and Quality (AHRQ) Amount: $34789
Abstract
The Annual Health Econometrics Workshop (AHEW), www.healtheconometrics.org, provides a forum to discuss the use of econometric and other quantitative methods to address issues in health economics and policy, health services research, and outcomes research. The meeting is the only one of its kind in North America and facilitates the exchange of ideas among the growing number of health econometricians around the world. It allows for the considerable exchange of ideas between junior and senior investigators in ways that no other health economics or econometrics workshop in the US does. AHEW was inaugurated in 2009. The 2012 – 2016 workshops were funded by an R13 grant from AHRQ 2013 (5R13HS021019) that provided the much-needed support to establish this workshop as a premier meeting in the world. We have seen record increases in paper submissions in last consecutive years. We are seeking renewal of our current R13 grant for the years 2017, 2018 and 2019. The venue for the 2017 workshop is tentatively planned at Washington University in St. Louis. Venues for 2018 - 2019 are not yet finalized. However, we have received overwhelming responses from researchers across the country offering to host these workshops. We seek funds to enable us to continue to build a strong workshop over the next three years and expand upon the scientific program to maximize participation and interaction, scientific content, and dissemination and training efforts.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY , Dept Of Pharmacy, eGC1 Preparer
Program on Genetic and Dietary Predictors of Drug Response in Rural and AI/AN.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 08/31/2018
Sponsor: National Institute of General Medical Sciences (NIGMS) Amount: $1622683
Abstract
Interindividual differences in pharmacological response contribute significantly to the morbidity and mortality often associated with therapeutic treatments of disease. Genetic variation represents a major, if not the dominant, source of this variability. Yet despite considerable research effort over the past 20 years to identify genetic causes of variable drug response, much remains unknown. We posit that this is the result in part of unrecognized gene-environment-drug (GED) and polygenic-drug (PGD) interactions. While the challenges in conducting research on these issues are considerable, we believe that significant inroads to understanding GED and PGD interactions can be made by developing sound mechanistic hypotheses and careful design of basic and translational studies. In this Program Project grant application, we propose three, highly interactive research Projects, and two supporting Cores, that together will develop and apply novel, generalizable approaches to understanding and predicting GED and PGD interactions in the context of preventing thromboembolic events in individuals with cardiovascular disease through the use of anticoagulation and antiplatelet drug therapies. Central to this effort will be our continued collaboration with American Indian and Alaska Native (AI/AN) populations of the Northwest and Alaska who have unique and often well-defined dietary and other environmental exposures that preliminary data suggests modify the coagulation pathway and platelet function; enrichment of unique, functionally important genotypes; and reduced genomic heterogeneity overall, compared to the general US population. Moreover, there is a strong moral imperative to conduct health research with AI/AN people, as they are often left out of such investigations and, thus, do not receive the potential benefits that such research can provide. Thus, our overall Program goals are to: 1) to advance our understanding of how genetic and environmental factors affect anti-coagulation and anti-platelet pharmacological responses, and 2) to more broadly improve the national environment for genomic research with AI/AN populations.
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, PHARMACEUTICS • Sabath, Daniel E., Key Personnel, Assoc Professor Without Tenure, LAB MEDICINE • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Calamia, Justina C., Other, Research Scientist/engineer 2, PHARMACEUTICS • McDonald, Matthew G., Other, Research Scientist/engineer 3, MEDICINAL CHEMISTRY • Sitko, Katherine A, Other, Research Scientist/engineer 2, GENOME SCIENCES • Stephany, Jason, Other, Research Scientist/engineer 2, GENOME SCIENCES • Trinidad, Susan B, Other, Research Scientist/engineer 4, BIOETHICS & HUMANITIES • Kavanaugh, Barbara, Other, Research Manager, PHARMACEUTICS • Rettie, Allan E., Co-Investigator, Professor, MEDICINAL CHEMISTRY • Thornton, Timothy, Co-Investigator, Associate Professor, BIOSTATISTICS • Fowler, Douglas M, Co-Investigator, Adjunct Assistant Professor, BIOENGINEERING • Xu, Libin, Co-Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Veenstra, David, Co-Investigator, Professor, DEPARTMENT OF PHARMACY • Burke, Wylie, Multiple PI, Professor, BIOETHICS & HUMANITIES • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS
Personalized Risk-AdaptIve Surveillance strategies in cancEr (PRAISE).
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 08/31/2018
Sponsor: National Institutes of Health (NIH) Amount: $414368
Abstract
This research addresses a significant problem in cancer survivorship care by using novel approaches and developing a practical tool to help resolve the uncertainty that clinicians and patients face when confronted with using new and evolving biomarker technologies to monitor for recurrence after patients have survived their primary cancer. Our holistic approach of applying the decision-making framework to three wide ranging cancer applications will inform both clinical decision-making in these areas and also future policy decisions on research investments with a transparent link between the needs for additional biomarker development and improving population outcomes.
Personnel
Bansal, Aasthaa, Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Basu, Anirban, Co-Investigator, Professor, DEPARTMENT OF PHARMACY • Veenstra, David, Co-Investigator, Professor, DEPARTMENT OF PHARMACY • Heagerty, Patrick J., Co-Investigator, Professor, BIOSTATISTICS • Shankaran, Veena, Co-Investigator, Assoc Professor Without Tenure, DEPARTMENT OF MEDICINE • Inoue, Lurdes, Co-Investigator, Professor, BIOSTATISTICS • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
RPPR Year 2 - Nucleoside modified mRNA based HIV vaccine.
HU, SHIU-LOK , Pharmaceutics
Award Date: 08/30/2018
Sponsor: University of Pennsylvania Amount: $444792
Abstract
The overall objective of this proposal is to explore novel approaches to prime an HIV envelope vaccine. The specific aims include a component of preclinical testing of immunogenicity in a non-human primate model system. All non-human primate work described in this project will be performed at the University of Washington under the direction of Dr. Shiu-Lok Hu.
Personnel
Hu, Shiu-Lok, Principal Investigator, Professor, PHARMACEUTICS • Firpo, Patricia S., Other, RESEARCH SCIENTIST/ENGINEER-SENIOR, Hu Lab - PRIMA, REGIONAL PRIMATE CTR • Cleveland, Bradley R., Other, RESEARCH SCIENTIST/ENGINEER 3, PCEUT - HU LAB, PHARMACEUTICS • Diamond, Deborah L, Other, RESEARCH MANAGER, PCEUT - ADMIN, PHARMACEUTICS • Guo, Wenjin, Other, RESEARCH SCIENTIST/ENGINEER 3, PCEUT - HU LAB, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Diamond, Deborah L, eGC1 Preparer, RESEARCH MANAGER, PCEUT - ADMIN, PHARMACEUTICS
Hepatic transport mechanisms of conjugated metabolites of sex steroids and AMG 853.
Prasad, Bhagwat , Pharmaceutics
Award Date: 08/27/2018
Sponsor: Amgen, Inc. Amount: $120000
Abstract
Sex steroids (e.g., testosterone and estradiol) and lipophilic compounds (e.g., AMG 853) are primarily eliminated by glucuronidation and/or sulfation in the hepatocytes (and enterocytes). While the uptake of the unconjugated steroids and AMG853 is mediated by the passive diffusion, the conjugated metabolites essentially require transporters for the efflux from the cells. The fate of conjugated metabolites depends on whether these are transported to the blood (sinusoidal efflux) or bile (canalicular efflux). While typically the hydrophilic conjugated metabolites in the blood are rapidly eliminated through kidneys which is also driven by their low binding to the plasma proteins, the conjugates which are eliminated in the intestine can be deconjugated by bacterial glucuronidases and sulfatases leading to enterohepatic recirculation. The conjugated metabolites can also be influxed by uptake transporters (organic anion transporting polypeptides, OATPs). Therefore, it is critical to elucidate the transport mechanisms of conjugated metabolites of testosterone, estradiol and AMG853 for the better prediction of their disposition including interindividual variability and drug-drug interactions.
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Contribution of altered lipid metabolism to resistance to cell envelope-targeting antimicrobials in MRSA.
Werth, Brian , Department Of Pharmacy
Award Date: 08/21/2018
Sponsor: National Institutes of Health (NIH) Amount: $463818
Abstract
TBA
Personnel
Werth, Brian, Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • Tomita, Hideaki, Key Personnel, Senior Fellow, MEDICINAL CHEMISTRY • Hines, Kelly Marie, Key Personnel, Senior Fellow, MEDICINAL CHEMISTRY • Salipante, Stephen, Co-Investigator, Asst Professor Without Tenure, LAB MEDICINE • Xu, Libin, Co-Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Cui, Yue, Co-Investigator, Asst Professor Without Tenure, ENVIRO & OCCUP HEALTH • Luetjen, Karen H., Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY
PRINCE (Proteomics-based Research Initiative for Non-CYP Enzymes).
Prasad, Bhagwat , Pharmaceutics
Award Date: 08/21/2018
Sponsor: Genentech, Inc. Amount: $50000
Abstract
The PRINCE program is a proposed research collaboration between the University of Washington and pharmaceutical industry to better elucidate the role of non-cytochrome P450 (non-CYP) enzymes in disposition, efficacy and toxicity of drugs. Overarching Objectives: •Characterization of subcellular localization, differential tissue expression and interindividual variability of non-CYP enzymes to develop whole body based physiological (i.e., PBPK) models to predict drug disposition •Quantitative proteomics characterization of in vitro and in vivo models of non-CYP enzymes
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
PRINCE (Proteomics-based Research Initiative for Non-CYP Enzymes).
Prasad, Bhagwat , Pharmaceutics
Award Date: 08/21/2018
Sponsor: Merck Sharp & Dohme Corp. Amount: $50000
Abstract
The PRINCE program is a proposed research collaboration between the University of Washington and pharmaceutical industry to better elucidate the role of non-cytochrome P450 (non-CYP) enzymes in disposition, efficacy and toxicity of drugs. Overarching Objectives: •Characterization of subcellular localization, differential tissue expression and interindividual variability of non-CYP enzymes to develop whole body based physiological (i.e., PBPK) models to predict drug disposition •Quantitative proteomics characterization of in vitro and in vivo models of non-CYP enzymes
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
PRINCE (Proteomics-based Research Initiative for Non-CYP Enzymes).
Prasad, Bhagwat , Pharmaceutics
Award Date: 08/21/2018
Sponsor: Gilead Sciences, Inc. Amount: $64772
Abstract
The PRINCE program is a proposed research collaboration between the University of Washington and pharmaceutical industry to better elucidate the role of non-cytochrome P450 (non-CYP) enzymes in disposition, efficacy and toxicity of drugs. Overarching Objectives: •Characterization of subcellular localization, differential tissue expression and interindividual variability of non-CYP enzymes to develop whole body based physiological (i.e., PBPK) models to predict drug disposition •Quantitative proteomics characterization of in vitro and in vivo models of non-CYP enzymes
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Disparities in the Availability of Cancer Clinical Trials: A Multi-level Analysis.
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 08/15/2018
Sponsor: National Institutes of Health (NIH) Amount: $77750
Abstract
Participation of minority populations in cancer clinical trials is vital to ensure generalizability of the results generated, facilitate discovery of novel therapies and therapeutic responses that are particularly relevant to traditionally underrepresented populations, and ensure equitable access to new and promising treatments. Yet more than twenty years after Congress mandated that the NIH ensure ‘sufficient and appropriate’ participation of minorities in clinical research, the participation rate of many minority populations remains substantially lower than the composition of the overall US population. Disparities in access to cancer clinical trials are a chief barrier to reducing disparities in trial participation. Thus it is critical to understand the role that geographic variation plays in driving disparities in access to cancer clinical trials if we are to design and target effective interventions to improve minority participation in such trials. Prior studies have had limited success in teasing apart the complex mix of site- and health care system-level factors that influence the availability of different types of cancer clinical trials for minority populations for two chief reasons. First, we currently lack a comprehensive database of sufficiently detailed trial-level characteristics or information about the locations where trials are launched because of the difficulty in synthesizing such information from multiple sources using traditional record linkage methods. As such, prior studies evaluating disparities in the availability of cancer clinical trials have been importantly limited in the range of factors examined and the number and type of trials studied. Second, cancer clinical trials are often launched at multiple sites that operate within larger healthcare systems, and individual recruiting sites often participate in multiple trials, which pose methodological challenges to disentangling the associations between various trial-, site-, and health care system-level factors on cancer clinical trial availability. We propose to address these challenges by integrating information from multiple sources using advanced record linkage methods and applying sophisticated modeling techniques to analyze the resulting multilevel data. The proposed study will improve understanding of how the availability of cancer clinical trials varies across geographic settings and the clinical trials portfolio, which could help target interventions and policies to address disparities in access to the areas most in need. This project will also lay the scientific foundation for a planned future study to predict enrollment of patient populations traditionally underrepresented in clinical research in publicly funded cancer clinical trials.
Personnel
Bansal, Aasthaa, Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY , Dept Of Pharmacy, eGC1 Preparer
Evaluating predictive methods and product performance in Healthy Adults for Pediatric Patients, Case Study: Furosemide.
PRASAD, BHAGWAT , Pharmaceutics
Award Date: 08/15/2018
Sponsor: Food and Drug Administration (FDA) Amount: $90993
Abstract
Poorly absorbed medications such as furosemide are common and recent experiments suggest that improvement in absorption can occur if these types of medications are consumed with liquids such as milk. The purpose of this study is to predict the absorption of furosemide in normal adults when taken with water, milk, baby formula, or Ensure. The model developed in this study will be used to make predictions how these liquids will affect drug absorption in children, potentially providing ways to improve medication absorption in children.
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Chapa, Revathi, Other, RESEARCH SCIENTIST/ENGINEER - ASSISTANT, PCEUT - P, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
VIRUS-LIKE PARTICLES WITH STABILIZED TRIMERIC ENVELOPE FOR PRIME BOOST IMMUNIZATION.
HU, SHIU-LOK , Pharmaceutics
Award Date: 08/09/2018
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) Amount: $615347
Abstract
To date, the only vaccine trial (RV144) that has shown any protective efficacy against HIV acquisition is basedon a poxvirus prime–protein boost immunization strategy. Although the efficacy achieved was modest (~31%),these findings provide a strong rationale to seek improvements for the prime-boost immunization approach andto gain better insight on the nature of the protective immunity achieved. In this application, we seek to improveresponses to prime boost immunization by a combination of three independent approaches: (i) to presentstabilized trimeric Env spikes on virus-like particles (VLP) as immunogens for vaccinia virus prime and VLPboost; (ii) to incorporate stabilized trimeric envelope (Env) from multiple isolates as polyvalent VLP immunogento increase the breadth of response; and (iii) to explore approaches that may increase the number of SOSIPtrimer spikes on VLP. Our overall working hypothesis is that the protective efficacy of prime-boostimmunization can be improved by optimizing immunogen and immunization regimen to enhance the breadthand potency of both neutralizing and non-neutralizing antibody responses that have been associated withprotection in human and/or non-human primate models. Specifically, we hypothesize that by presentingstabilized trimeric Env on VLP in the poxvirus-protein prime boost regimen, we will be able to enhanceneutralizing antibody responses, and by using polyvalent Env and increasing the density of Env spikeson the VLP immunogens, we will further amplify the breadth and the potency of response. Theenhanced breadth and potency of both neutralizing and non-neutralizing antibody responses,including V1/V2-directed antibodies and those that mediate antiviral effector functions, such as ADCC,will contribute to the protective efficacy of the poxvirus-protein prime boost immunization platform.The Specific Aims of this proposal are: (1) To determine the structure and the antigenic and immunogenicprofiles of stabilized Env trimers incorporated into VLP; (2) To determine if stabilized Env trimers from multipleisolates can be incorporated on VLP and if such polyvalent vaccines when used in a prime/boost regimen willincrease the breadth of Nab and non-Nab responses; (3) To determine if cytoplasmic tail modifications willincrease the density of stabilized Env spikes on VLP and if increased Env density will enhance the breadth andpotency of Env specific responses; and (4) To examine if immunization regimens down-selected from thepreceding studies in rabbits can be translated to macaques. If successful, insights obtained from these studieswill inform the clinical development of vaccines and vaccine strategies that may be more effective than thoseused in RV144 to prevent HIV-1 acquisition in humans.
Personnel
Hu, Shiu-Lok, Principal Investigator, Professor, PHARMACEUTICS • Yang, Lifei, Other, Research Associate, PHARMACEUTICS • Cleveland, Bradley R., Other, Research Scientist/engineer 3, PHARMACEUTICS • Lee, Kelly K., Co-Investigator, Associate Professor, MEDICINAL CHEMISTRY • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Targeting novel pathways to enhance gastrointestinal integrity during HIV infection.
KLATT, NICHOLE , Pharmaceutics
Award Date: 08/09/2018
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Amount: $36013
Abstract
The pathology of disease caused by HIV infection is complex and multifaceted. HIV infection results in a vicious cycle of mucosal damage, chronic inflammation and overall immunological dysfunction, which are closely associated with disease, and are not ameliorated with antiretroviral therapy (ART). This chronic inflammation is strongly associated with gastrointestinal (GI) mucosal barrier damage and microbial translocation, which also do not resolve completely with ART. Furthermore, mucosal dysfunction is associated with increased morbidities and mortality in HIV-infected individuals. Thus, it is imperative that novel therapeutic strategies aimed at enhancing mucosal function are developed. However, it is still unclear what pathways lead to damage to the GI tract during HIV infection, and thus a substantial hurdle for the development of targeted therapies. Here, our global hypothesis is that an inflammatory proteome comprised of neutrophil secretions in the GI tract is driven by microbiome dysbiosis, and is the mechanism underlying tight epithelial barrier disruption and mucosal dysfunction. We will test these hypotheses in HIV-infected individuals with high versus low disease pathogenesis profiles (measured by CD4/CD8 ratio), as well as in uninfected individuals, in the following aims: (I) We will assess whether an altered gastrointestinal proteome underlies mucosal dysfunction in HIV infection; (II) We will determine if neutrophil accumulation and dysfunction in the GI tract results in this inflammatory GI proteome; (III) We will assess whether the mechanism underlying neutrophil dysfunction and accumulation is HIV-associated microbiome dysbiosis. We will use novel data-driven modeling approaches to provide systems level insight of these complex relationships. Our ultimate goal is to define mechanisms and novel targets for therapeutic interventions by identifying pathways associated with mucosal inflammation and epithelial damage in HIV-infected individuals.
Personnel
Klatt, Nichole, Principal Investigator, Asst Professor Without Tenure, PHARMACEUTICS • Helgeson, Eric J., Other, Registered Nurse 1 - Research, DEPARTMENT OF MEDICINE • Padullo, Emilda M., Other, Program Operations Specialist, DEPARTMENT OF MEDICINE • Jonsson, Christine Anne, Other, Research Consultant, DEPARTMENT OF MEDICINE • Storey, Sheryl S., Other, Health Care Specialist, DEPARTMENT OF MEDICINE • Louella, Michael W., Other, Program Coordinator, DEPARTMENT OF MEDICINE • Collier, Ann C, Co-Investigator, Professor Without Tenure, DEPARTMENT OF MEDICINE • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Oxysterols in SLOS neurodevelopment: pathological role and therapy.
XU, LIBIN , Medicinal Chemistry
Award Date: 08/02/2018
Sponsor: National Institutes of Health (NIH) Amount: $391101
Abstract
Defects in cholesterol biosynthesis lead to disorders that affect brain development, with Smith-Lemli-Opitz syndrome (SLOS) being the most common. SLOS is caused by mutations in the gene encoding 3ß-hydroxysterol-?7-reductase (DHCR7). This results in decreased levels of cholesterol and greatly increased levels of a cholesterol precursor, 7-dehydrocholesterol (7-DHC), in tissues and fluids of SLOS patients relative to normal individuals. The SLOS phenotype manifests as multiple congenital malformations, nervous sys-tem abnormalities, and autistic behavior. In fact, over 50% of SLOS children were diagnosed with autism, which is one of the strongest correlations between autism and single gene disorders. Conventional therapy for SLOS is supplementation of cholesterol, sometimes in combination with simvastatin, but these approaches do not improve neurological defects in patients. The long-term goals of this project are to elucidate the consequences of disrupted cholesterol homeostasis during neurodevelopment and to develop therapies that can ameliorate the neurological defects. We hypothesize that 7-DHC-derived oxysterols are causative factors for neurodevelopmental defects in SLOS. In this project, we will evaluate the pathological roles of 7-DHC oxysterols in neurogenesis processes in vitro and in vivo and test therapeutic approaches that can lower the levels of these oxysterols or counteract their biological actions. The knowledge generated from this study is likely to have significant impact on other diseases that are related to abnormal cholesterol biosynthesis and autism.
Personnel
Xu, Libin, Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Gamble, Lara J., Co-Investigator, Research Associate Professor, BIOENGINEERING • Xia, Zhengui, Co-Investigator, Professor, ENVIRO & OCCUP HEALTH • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Lee, Erik, Budget Contact, Budget/fiscal Analyst, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
Effectiveness of Gastric Sleeve vs. Gastric Bypass for Cardiovascular Disease Y3.
BASU, ANIRBAN , Department Of Pharmacy
Award Date: 08/02/2018
Sponsor: Kaiser Permanente Amount: $320834
Abstract
Bariatric surgery is one of the most effective treatment strategies for weight loss in the severely obese. Currently, two operations constitute the majority of these procedures: Vertical Sleeve Gastrectomy (VSG), the newest restrictive procedure, in which only stomach size is reduced, and Roux-en-Y Gastric Bypass (RYGB), the ‘gold standard’ procedure, in which gastric capacity is similarly limited but with an additional modest bypass of a section of small intestine. From 2008-2011, there was a ~5-fold increase in use of VSG in North America (from 4% to 19%); in contrast, use of RYGB declined from 51% to 47%. If trends continue, VSG may comprise up to 50% or more of all bariatric procedures by 2020. The reasons for this dramatic shift in procedural preference are unknown, but it is likely due to the perception of surgeons that VSG and RYGB are at clinical equipoise, but VSG is easier to perform, less expensive, and has fewer complications. A clear evidence base to support these perceptions does not exist. Current clinical knowledge suffers from two major gaps. GAP 1: Very few studies have included many important cardiovascular health outcomes. Comparative changes with RYGB and VSG in prevalent cardiovascular disease (CVD) risk factors such as hypertension and dyslipidemia, as well as overall CVD risk, have not been studied. There is also almost nothing known about the comparative safety of VSG and RYGB beyond the standard reporting period of 30 days after surgery. GAP 2: Almost nothing has been published regarding the heterogeneity in comparative effectiveness and safety between these two procedures. Even among the few small published comparative studies, there is no understanding of how heterogeneity in effects might determine which procedure is most appropriate for certain kinds of patients. Our own preliminary work clearly shows that racial/ethnic minority patients have different weight loss responses to RYGB (losing less weight) but similar responses to VSG (no difference in weight loss), compared to whites. Given these major gaps in knowledge, large-scale comparative effectiveness studies, using real-world clinical populations are urgently needed to improve bariatric treatment decision-making for severely obese patients, especially with respect to CVD outcomes. We have designed such a study to compare the effectiveness of VSG and RYGB for hypertension, dyslipidemia, and diabetes remission as well as overall CVD risk reduction in more than 17,000 VSG and 11,000 RYGB patients, from a real-world health care setting with an integrated electronic medical record. This combined sample size is over 20 times the number of VSG and RYGB patients that have been directly compared in case series and controlled trials to date (n = 1,041). No other studies in the literature have the diversity of bariatric surgery patients in our sample, who are 56% Hispanic or non-Hispanic Black. We will apply innovative econometric techniques to deal with selection biases in observation data and study heterogeneity in effects to inform clinical knowledge and identify areas where further studies are needed. We have assembled an experienced, interdisciplinary research and clinical care team to address the following specific aims over a median three years of follow-up.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Barthold, Douglas G., Key Personnel, Research Assistant Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY , Dept Of Pharmacy, Budget Contact • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Predicting Fetal Drug Exposure with a Maternal-Fetal PBPK Model.
Unadkat, Jashvant D , Pharmaceutics
Award Date: 07/30/2018
Sponsor: Bill and Melinda Gates Foundation Amount: $344914
Abstract
Pregnant women are administered medications for various preexisting or pregnancy-induced conditions. These medications may present risk of toxicity or lack of efficacy to the fetus. Therefore, it is important to understand drug exposure and pharmacological effects on the fetus upon maternal drug administration at various gestational ages. However, for ethical reasons, drug exposure and effects in the fetus are not easily studied in clinic. Physiologically-based pharmacokinetic (PBPK) models incorporate physiological and drug-related information into a virtual trial design to predict drug exposure in silico. They present a unique and valuable tool for comprehensive understanding of interactions between drug molecule and human physiology. Depending on the questions to be addressed and the confidence in a maternal-fetal PBPK (m-f-PBPK) model structure, simulations can be useful to support dose selection in pregnant women to ensure safety and efficacy of drugs transferred to the fetus. A prototype m-f-PBPK model has been published by Zhang et al, 2017[1,2] by the Principal Investigator at the University of Washington. The model successfully predicted fetal exposure to drugs that passively diffuse across the placenta and incorporated the effect of gestational age, and developmental changes in the fetus. With continuing verification and addition of parameters relevant to feto-placental transport and metabolism, the model can be expanded to make fetal drug exposure predictions for more medications. Such predictions are important to support safe and effective use of therapeutic drugs administered to pregnant women.
Personnel
Unadkat, Jashvant D, Principal Investigator, Professor, PHARMACEUTICS • Anoshchenko, Olena, Other, PREDOCTORAL RESEARCH ASSOCIATE 2, PCEUT - GRADUATE, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
UW Patient Centered Outcomes Research Institutional Mentored Career Development Program (K12).
SULLIVAN, SEAN , Department Of Pharmacy
Award Date: 07/27/2018
Sponsor: Agency for Healthcare Research and Quality (AHRQ) Amount: $731961
Abstract
This program aims to develop early career scientists in PCOR evidence development, adoption and evaluation. At the completion of their training, Scholars will have cutting edge PCOR skills and a grounding in implementation and dissemination science. Our overall aims are to (1) provide Scholars with multidisciplinary training, (2) activate Scholars to utilize existing and unparalleled opportunities within the UW and affiliated institutions to learn PCOR and CER from experts with ongoing projects, multidisciplinary teams, data resources, and real world populations and stakeholders, (3) create an environment that supports the early research efforts of junior faculty, infuses them with the excitement of comparative effectiveness research and nurtures their early career development and productivity and aids in ensuring a long term career in conducting and teaching PCOR.
Personnel
Sullivan, Sean, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Devine, Emily E., Mentor, Associate Professor, DEPARTMENT OF PHARMACY • Patrick, Donald L., Mentor, Professor, HEALTH SERVICES/MAIN • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Kraegel, Paul K., Budget Contact, Program Operations Specialist, DEPARTMENT OF PHARMACY • Kraegel, Paul K., eGC1 Preparer, PROGRAM OPERATIONS SPECIALIST, Pharm - Admin, DEPARTMENT OF PHARMACY
Targeted Long-acting Combination Antiretroviral Therapy (TLC-ART) 5UM1 AI120176.
HO, RODNEY J.Y. , Pharmaceutics
Award Date: 07/19/2018
Sponsor: National Institutes of Health (NIH) Amount: $2946499
Abstract
The overarching purpose of the University of Washington Targeted Long-acting Combination Antiretroviral Therapy (UW TLC-ART) program is to develop one or more safe, stable, scalable and tolerable long acting antiretroviral combination for treatment of HIV infection in collaboration with NIH program staff. Leveraging the multidisciplinary, translational expertise and research infrastructure available at the University of Washington, this strategic drug development program integrates experts in statistics and mathematics, HIV adult clinical trials, behavioral science, regulatory affairs, scientific and executive leadership and business management, pharmaceutical sciences including drug targeting, delivery, metabolism and pharmacokinetics, retro virology, HIV primate models, preclinical pharmacology and toxicology, and mucosal immunology. The program has established collaborations with major pharmaceutical industry and other stakeholders to provide resources essential for the strategic development plan and potential future partnerships for product development. The program will also be guided by an external scientific advisory board (SAB) as well as an internal advisory group. We plan to develop three unique antiretroviral drug combination compositions/formulations following a carefully monitored timeline. The drug combination choices are based on current antiretroviral combinations with demonstrated safety and efficacy. Additionally these drugs have known relationships between drug levels and therapeutic effect. The UW TLC-ART program is based on demonstrated capability to produce drug combination particles that achieve therapeutic plasma drug concentrations lasting over seven days in a primate model. After subcutaneous injection, these compositions/formulations distribute widely throughout the lymphatic system. The program’s strategic development decisions will be based on the desired target product profile and progress on milestones of the drug development timeline. These decisions will guide prioritization of program resources to facilitate the program goal.The program proposes to develop three combinations and will use progress on milestones, external information and the SAB to prioritize TLC-ART candidates advancing for further development. The program has eleven sections organized in 5-aims designed to interact in an integrated and collaborative way to achieve the program goal. To support the drug development, the program proposes three hypothesis driven projects that will enhance the understanding of the distribution characteristics and safety using both pharmacokinetic/pharmacodynamics modeling and in vivo studies. While ambitious, the proposed 5-year program has well integrated experience and expertise committed to make substantial progress in develop one or more targeted long acting retroviral treatment.
Personnel
Ho, Rodney J.Y., Principal Investigator, Professor, PHARMACEUTICS • Lane, Sarah, Other, RESEARCH SCIENTIST/ENGINEER 2, PCEUT - HO LAB, PHARMACEUTICS • Gulati, Gaurav Kumar, Other, Research Scientist Engineer 3, PHARMACEUTICS • Mu, Qingxin, Other, RESEARCH SCIENTIST/ENGINEER 3, PHARM:Pharmaceutics, PHARMACEUTICS • Doenges, April A., Other, PROGRAM COORDINATOR, PHARMACEUTICS • Shireman, Laura M., Other, RESEARCH COORDINATOR, PCEUT - SHEN LAB, PHARMACEUTICS • Yu, Jesse, Other, Graduate Fellow Stipend w/ Benefits, PHARMACEUTICS • Perazzolo, Simone, Other, Senior Fellow, PHARMACEUTICS • Koehn, Josefin, Other, Research Scientist/engineer 1, PHARMACEUTICS • Jonsson, Christine Anne, Other, Research Consultant, DEPARTMENT OF MEDICINE • Holte, Sarah E., Other, Affiliate Associate Professor, BIOSTATISTICS • Kraft, John C, Other, Predoctoral Research Associate 2, PHARMACEUTICS • Tapia, Kenneth A, Other, Research Consultant, GLOBAL HEALTH • Hughes, Sean M, Other, Research Technologist 2, OBGYN/ADMIN • McConnachie, Lisa, Other, Research Scientist/engineer 4, PHARMACEUTICS • Kinman, Loren M., Other, Research Scientist/engineer 3, PHARMACEUTICS • Firpo, Patricia S., Other, Research Scientist/engineer-senior, REGIONAL PRIMATE CTR • Diamond, Deborah L, Other, Research Manager, PHARMACEUTICS • Tian, Baoping, Other, Research Scientist/engineer 2, PHARMACEUTICS • Shen, Danny D, Co-Investigator, Professor, PHARMACEUTICS • Simoni, Jane M, Co-Investigator, Professor, PSYCHOLOGY • Treuting, Piper, Co-Investigator, Assoc Professor Without Tenure, COMPARATIVE MEDICINE • Hladik, Florian, Co-Investigator, Research Associate Professor, OBGYN/ADMIN • Hu, Shiu-Lok, Co-Investigator, Professor, PHARMACEUTICS • Collier, Ann C, Multiple PI, Professor Without Tenure, DEPARTMENT OF MEDICINE • Jonsson, Christine Anne, Administrative Contact, Research Consultant, DEPARTMENT OF MEDICINE • Jonsson, Christine Anne, Budget Contact, Research Consultant, DEPARTMENT OF MEDICINE • Jonsson, Christine Anne, eGC1 Preparer, MANAGER OF PROGRAM OPERATIONS, Department of Medic, DEPARTMENT OF MEDICINE
The University of Washington, School of Pharmacy Research Affiliates Program on Transporters (UWRAPT).
UNADKAT, JASHVANT D , Pharmaceutics
Award Date: 07/12/2018
Sponsor: Genentech, Inc. Amount: $70000
Abstract
The goal of this project is to establish a Research Affiliates Program at the UW within the School of Pharmacy. The RAP will bring together UW researchers and industry partners interested in furthering research to elucidate and quantify the role of transporters in the absorption, disposition, efficacy and toxicity of drugs..
Personnel
Unadkat, Jashvant, Principal Investigator, Professor, PHARMACEUTICS • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Eng, Matthew N., Budget Contact, Administrator, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Drug Action, Metabolism and Kinetics.
ATKINS, WILLIAM M. , Medicinal Chemistry
Award Date: 07/06/2018
Sponsor: National Institute of General Medical Sciences (NIGMS) Amount: $468232
Abstract
The primary objective of this Pharmacological Sciences Training Grant is to develop scientists, equipped with the necessary background in the biological and chemical sciences, and training in the application of modern tools of research and instrumental techniques, to undertake and direct fundamental research related to drug action, metabolism and kinetics.Trainees follow tracks that emphasize training in four broadly defined areas; (I) drug metabolism, (II) pharmacokinetics, drug transport and delivery, (III) cellular and molecular pharmacology and (IV) structure and drug design, that presently exist in the departments of Medicinal Chemistry, Pharmaceutics and Pharmacology.Didactic components involve individualized, highly multidisciplinary programs of coursework and seminars that center around the biological and chemical sciences. Research components of the program emphasize training in mechanistic and bioanalytical aspects of drug metabolism and toxicology, pharmacokinetics and pharmacodynamics, drug transporter function and regulation, pharmacogenetics, mechanisms and regulation of cell signaling, neuropharmacology and X-ray, NMR and proteomic approaches to structure elucidation of protein-ligand interactions of pharmacological interest.
Personnel
Atkins, William M., Principal Investigator, Professor, MEDICINAL CHEMISTRY • Guttman, Miklos, Mentor, Assistant Professor, MEDICINAL CHEMISTRY • Bajjalieh, Sandra M., Mentor, Professor, PHARMACOLOGY • Catterall, William A, Mentor, Chair, PHARMACOLOGY • Chavkin, Charles, Mentor, Professor, PHARMACOLOGY • Cirulli, VINCENZINO, Mentor, Adjunct Associate Professor, PHARMACOLOGY • Cook, David G., Mentor, Adjunct Research Assoc Prof, PHARMACOLOGY • Gardner, Richard G., Mentor, Associate Professor, PHARMACOLOGY • Hague, Chris, Mentor, Associate Professor, PHARMACOLOGY • Ho, Rodney J.Y., Mentor, Professor, PHARMACEUTICS • Hol, Wilhelmus G.J., Mentor, Adjunct Professor, PHARMACOLOGY • Hu, Shiu-Lok, Mentor, Professor, PHARMACEUTICS • Isoherranen, Nina, Mentor, Associate Professor, PHARMACEUTICS • Kalume, Franck, Mentor, Adjunct Assistant Professor, PHARMACOLOGY • Kelly, Edward J, Mentor, Assoc Professor Without Tenure, PHARMACEUTICS • Klatt, Nichole, Mentor, Asst Professor Without Tenure, PHARMACEUTICS • Kunze, Kent, Mentor, Acting Chair, MEDICINAL CHEMISTRY • Lee, Kelly K., Mentor, Assistant Professor, MEDICINAL CHEMISTRY • Lin, Yvonne S., Mentor, Asst Professor Without Tenure, PHARMACEUTICS • Mao, Qingcheng, Mentor, Associate Professor, PHARMACEUTICS • Mc Knight, G Stanley, Mentor, Professor, PHARMACOLOGY • Moon, Randall T, Mentor, Professor, PHARMACOLOGY • Nath, Abhinav, Mentor, Assistant Professor, MEDICINAL CHEMISTRY • Nathanson, Neil, Mentor, Professor, PHARMACOLOGY • Ong, Shao-En, Mentor, Assistant Professor, PHARMACOLOGY • Phillips, Paul, Mentor, Associate Professor, PHARMACOLOGY • Scott, John D, Mentor, Professor, PHARMACOLOGY • Shen, Danny D, Mentor, Professor, PHARMACEUTICS • Stella, Nephi, Mentor, Professor, PHARMACOLOGY • Storm, Daniel R, Mentor, Professor, PHARMACOLOGY • Thummel, Kenneth E., Mentor, Professor, PHARMACEUTICS • Totah, Rheem A., Mentor, Associate Professor, MEDICINAL CHEMISTRY • Unadkat, Jashvant D, Mentor, Professor, PHARMACEUTICS • Wang, Edith H., Mentor, Associate Professor, PHARMACOLOGY • Wang, Joanne, Mentor, Professor, PHARMACEUTICS • Zheng, Ning, Mentor, Professor, PHARMACOLOGY • Zweifel, Larry, Mentor, Assistant Professor, PHARMACOLOGY • Rettie, Allan E., Mentor, Professor, MEDICINAL CHEMISTRY • Prasad, Bhagwat, Mentor, Asst Professor Without Tenure, PHARMACEUTICS • Xu, Libin, Mentor, Assistant Professor, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Lee, Erik, Budget Contact, Budget/fiscal Analyst, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
Hybrid structural mass spectrometry for rapid site-specific glycan structural elucidation.
GUTTMAN, MIKLOS , Medicinal Chemistry
Award Date: 06/26/2018
Sponsor: National Institutes of Health (NIH) Amount: $439210
Abstract
A wide variety of complex sugar structures cover most of the extracellular milieu of higher level organisms. Many of the sugars regulate host-pathogen interactions and modulate the immune system. Understanding the detailed structures of the sugars that are associated with disease onset can identify ways of preventing pathogens from infecting cells and provide better ways to detect and target cancer cells. The current proposal aims to implement recent developments in gas-phase structural analysis into existing platforms for glycobiology to provide a novel analytical tool. Such a rapid technology will be necessary for enabling large scale studies to better understand regulation of the immune response, tumor progression, and characterization of the next generation of biotherapeutics.
Personnel
Guttman, Miklos, Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Mookherjee, Abhigya, Other, Senior Fellow, MEDICINAL CHEMISTRY • Harkewicz, Richard, Other, Project Appointment - Overtime Exempt, MEDICINAL CHEMISTRY • Hines, Kelly Marie, Other, Senior Fellow, MEDICINAL CHEMISTRY • Xu, Libin, Co-Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Bush, Matthew Francis, Co-Investigator, Assistant Professor, CHEMISTRY • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Lee, Erik, Budget Contact, Budget/fiscal Analyst, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, Administrator, MEDICINAL CHEMISTRY
CYP2J2 mediated eicosanoids in arrhythmias and sudden cardiac arrest.
TOTAH, RHEEM A. , Medicinal Chemistry
Award Date: 06/14/2018
Sponsor: National Institutes of Health (NIH) Amount: $721142
Abstract
Sudden cardiac arrest (SCA) is a major public health concern, accounting for up to 400,000 deaths in the US alone. Despite recent progress in treatment and prevention of coronary artery disease, SCA continues to be one of the leading causes of mortality. With the exception of the implantable cardioverter-defibrillator (ICD), there are few effective approaches to SCA prevention and even fewer clues to identify individuals predisposed to underlying life-threatening arrhythmias.Epoxyeicsatrienoic acids (EETs) are important cardiac signaling lipid metabolites of arachidonic acid through the cytochrome P450 (CYP) pathway. In humans, CYP2J2 is the main enzyme responsible for EET biosynthesis in cardiac tissue. CYP2J2 is differentially regulated in various cell types and decline in expression or activity results in lower EETs in cardiomyocytes, which can be detrimental to cell. This research will identify if there is an association between SCA and EET levels in plasma or red blood cells. The protective mechanism of EETs in the heart will also be examined and factors that regulate CYP2J2, the EET generator in cardiac tissue, will be revealed. Once completed, this research will help uncover factors that lead to SCA and discover potential new drug targets that will make prediction and prevention much easier.
Personnel
Totah, Rheem A., Principal Investigator, Associate Professor, MEDICINAL CHEMISTRY • Denham, Julie E, Other, RESEARCH SCIENTIST/ENGINEER 3, MEDICINAL CHEMISTRY • Gallis, Byron M., Other, RESEARCH SCIENTIST/ENGINEER 2, MedChem - Totah Lab, MEDICINAL CHEMISTRY • Jensen, Paul N, Other, RESEARCH SCIENTIST/ENGINEER 4, Department of Medic, DEPARTMENT OF MEDICINE • Zeigler, Maxwell Bertrand, Other, Research Scientist/Engineer 3 (E S 8), MEDICINAL CHEMISTRY • Guo, Xiaoyun, Other, Senior Fellow, PHYSIOLOGY & BIOPHYSIC • Murphy, Karen Jackson, Other, BUDGET/FISCAL ANALYST LEAD, Department of Medicine, DEPARTMENT OF MEDICINE • Evangelista, Eric A, Other, Research Assistant (E S UAW ASE), MEDICINAL CHEMISTRY • Aliwarga, Theresa, Other, Research Assistant (E S UAW ASE), MEDICINAL CHEMISTRY • Gharib, Sina A., Co-Investigator, Assoc Professor Without Tenure, DEPARTMENT OF MEDICINE • Lemaitre, Rozenn N., Co-Investigator, Research Associate Professor, DEPARTMENT OF MEDICINE • Liu, Qinghang, Co-Investigator, Assistant Professor, PHYSIOLOGY & BIOPHYSIC • Sotoodehnia, Nona, Multiple PI, Assoc Professor Without Tenure, DEPARTMENT OF MEDICINE • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY
Variation of vitamin D metabolism and regulatory genes in the Yup’ik population.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 06/14/2018
Sponsor: National Institutes of Health (NIH) Amount: $61174
Abstract
Vitamin D levels vary seasonally with sunlight availability and with differences in diet. Seasonal variation of vitamin D levels is especially apparent at high latitudes where adequate sunlight may not be available, such as in Yup’ik Alaska Native communities living within the Arctic Circle (66°33’N). Previous research has shown that a traditional diet high in marine-mammals and fish may contribute to the high levels of vitamin D in Yup’ik people, but recent trends show that the traditional diet intake is declining due to shifts to more Westernized foods, and this may result in vitamin D inadequacy. Genetic variation in vitamin D pathway and target genes is also important to the circulating levels of vitamin D. Many studies have shown that low levels of vitamin D are associated with cancer and cardiometabolic disease (i.e. cardiovascular disease and Type 2 diabetes). The Yup’ik people may have a protective advantage against T2D because of their high levels of vitamin D due to diet, but this is changing as younger generations of Yup’ik consume less traditional foods and have lower levels of vitamin D. This proposal seeks to determine genetic variant information in vitamin D homeostasis pathway and target genes and how this relates to circulating vitamin D concentrations, traditional diet, and cardiometabolic risk factors (fasting glucose, BMI, HbA1c) in Yup’ik people.
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, PHARMACEUTICS • Claw, Katrina G., Fellow, Senior Fellow, PHARMACEUTICS • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Functional Dynamics of P-glycoprotein.
ATKINS, WILLIAM M. , Medicinal Chemistry
Award Date: 06/13/2018
Sponsor: National Institutes of Health (NIH) Amount: $29886
Abstract
This project aims to understand the mechanism of a protein, P-glycoprotein, that contributes to cancer cell drug resistance and the clearance and pharmacokinetics of most drugs. The mechanism by which P-glycoprotein (P-gp) recognizes and exports such a wide range of drugs is not known. P-gp utilizes the hydrolysis of ATP for the energy required to pump drugs out of cells but the coupling between ATP hydrolysis and drug export is not known. The major hypothesis of this proposal is that different drugs elicit different conformations of P-gp that differentially favor ATP hydrolysis. With a better understanding of P-gp mechanism, it will be possible to design P-gp inhibitors to improve the efficacy of anticancer drugs or to improve the pharmacokinetics of other drugs.
Personnel
Atkins, William M., Principal Investigator, Professor, MEDICINAL CHEMISTRY • Dabrowski, Michael J., Other, Research Scientist/engineer 2, MEDICINAL CHEMISTRY • Li, Jiarong Mavis, Other, Predoctoral Research Associate 2, MEDICINAL CHEMISTRY • Nath, Abhinav, Co-Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Lee, Erik, Budget Contact, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
Effects of Retinoids on CYP2D6 Activity and Variability in Special Populations.
HEBERT, MARY F , Department Of Pharmacy
Award Date: 06/13/2018
Sponsor: National Institutes of Health (NIH) Amount: $57867
Abstract
CYP2D6, a key drug-metabolizing enzyme, is involved in the metabolism of ~20% of all drugs. We hypothesize that natural variation in retinoic acid concentrations and retinoid signaling in the liver regulate CYP2D6 expression and activity in humans, which in turn contributes to CYP2D6 pharmacokinetic variability and CYP2D6 induction during pregnancy. We will take a mechanistic approach and test the relationship between retinoid concentrations and CYP2D6 activity in 2 studies evaluating from the perspective of CYP2D6 induction during pregnancy, repression of induction with vitamin A administration and repression of normal CYP2D6 activity with 13-cis-retinoic acid (isotretinoin) in non-pregnant adolescent patients. Pregnant and adolescent patients often require treatment for chronic conditions, which can include CYP2D6 substrates. After accounting for genetic variation, there is still a great deal of unaccounted variability in CYP2D6 activity in these special populations making clinical management challenging. Basic science studies suggest that retinoids play an important role in CYP2D6 regulation. Our objective is to understand the role of retinoids in CYP2D6 activity in pregnant, postpartum and adolescent patients and translate new laboratory findings into humans. Our Specific Aims are: Specific Aim 1. To determine if vitamin A administration decreases CYP2D6 activity during pregnancy. In this aim, we will evaluate the effect of vitamin A administration on pregnancy-induced CYP2D6 activity. This study will provide mechanistic understanding of CYP2D6 induction and variability during pregnancy as well as provide a potential clinical strategy for management of pregnant women that require CYP2D6 substrates.Specific Aim 2. To investigate if isotretinoin (13-cis-retinoic acid) administration decreases CYP2D6 activity in adolescent patients. In this aim, we will conduct a drug-drug interaction study evaluating the effects of 13-cis-retinoic acid on non-induced CYP2D6 activity in adolescent patients. Secondary analysis will evaluate the relationship between retinoid concentrations and CYP2D6 activity in these special populations. In both Specific Aims we will utilize dextromethorphan as our CYP2D6 probe substrate. Through these complementary aims, we will be the first to conduct mechanistic testing of endogenous regulation of CYP2D6 activity in humans. The results could overcome a critical barrier to safe and effective administration of CYP2D6 substrates in adolescent and pregnant patients. Based on our compelling preliminary data, we expect to identify a novel mechanism of CYP2D6 regulation in humans and a potential management strategy for CYP2D6 induction and variability during pregnancy, with the intention of improving safety and efficacy of medications for these vulnerable patients. This work is critical for the provision of individualized therapy and along with genetics, the first step in development of an endogenous biomarker for CYP2D6 activity.
Personnel
Hebert, Mary F, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Easterling, Thomas R, Key Personnel, Professor Without Tenure, OBGYN/ADMIN • Isoherranen, Nina, Key Personnel, Associate Professor, PHARMACEUTICS • Vary, James, Key Personnel, Asst Professor Without Tenure, DEPARTMENT OF MEDICINE • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Structure, dynamics and variation in influenza hemagglutinin-driven fusion.
LEE, KELLY K. , Medicinal Chemistry
Award Date: 05/31/2018
Sponsor: National Institutes of Health (NIH) Amount: $396667
Abstract
The influenza hemagglutinin fusion glycoprotein (HA) performs the essential function of targeting host cells for infection and mediating entry and delivery of the viral genome. Here we propose to apply innovative structural, biophysical and deep sequencing approaches to probe structural and functional variation among diverse influenza HA glycoproteins and variants of influenza virus that exhibit different overall morphologies. A more complete understanding of HA-mediated membrane fusion and the extent to which this process is conserved among diverse influenza virus strains can provide valuable new information to improve the design and targeting of antiviral agents and may be valuable for selection of vaccine immunogens.
Personnel
Lee, Kelly K., Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Williams, James A., Other, Research Assistant (E S UAW ASE), MEDICINAL CHEMISTRY • Mangala Prasad, Vidya, Other, Senior Fellow, MEDICINAL CHEMISTRY • Hom, Nancy, Other, Senior Fellow, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Lee, Erik, Budget Contact, Fda Seiu - Project, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
The plasma membrane monoamine transporter (PMAT): expression and role in mIBG disposition in neuroblastoma.
WANG, JOANNE , Pharmaceutics
Award Date: 05/30/2018
Sponsor: National Institutes of Health (NIH) Amount: $372175
Abstract
The long term goal of this project is to understand the physiological function of plasma membrane monoamine transporter (PMAT) and its roles in the disposition and action of xenobiotics. Previous work established PMAT as a monoamine and a polyspecific organic cation transporter expressed on the cell plasma membrane in normal tissues. While the physiological function of PMAT and its role in organic cation disposition have been characterized, little is known regarding its expression and function in diseased tissues. Recently, we and others found that PMAT is highly expressed in human neuroblastoma (NB) tissues and cell lines. Our preliminary data suggest that PMAT is aberrantly localized in intracellular organelles in human NB cells, in contrast to its normal cell surface expression. The aberrant intracellular localization of PMAT in NB cells is associated with the presence and increased expression of an alternatively spliced variant. Furthermore, we found that meta-iodobenzylguanidine (mIBG), a radiopharmaceutical used in both diagnosis and treatment of NB, is avidly transported by PMAT. Cellular uptake and retention of 131I-mIBG in tumor cells is crucial for its anti-tumor activity. Based on these data, we hypothesized that PMAT is a novel, previously unrecognized transporter involved in intracellular disposition and therapeutic efficacy of 131I-mIBG in NB. This competing renewal application focuses on understanding the expression and cellular localization of PMAT in NB and its role in systemic disposition and tumor retention of mIBG. Three specific aims are proposed. In Aim 1, we will first determine the expression and cellular localization of PMAT in NB tissues and cells by mRNA analysis, protein quantification, and immuno-colocalization studies. The functional significance of PMAT in cellular mIBG disposition will be evaluated using cultured human NB cells with stable silencing of the PMAT gene. In Aim 2, we will determine the role of the alternatively spliced variant in regulating membrane trafficking and intracellular retention of PMAT by co-transfection and co-immunoprecipitation studies. In Aim 3, we will determine the in vivo significance of PMAT in mIBG systemic disposition, tumor retention and response using a Pmat knockout model and a murine xenograft model. The proposed studies will uncover a novel molecular mechanism underlying mIBG intracellular uptake and retention in its target cells. As 131I-mIBG therapy is currently being investigated as a frontline treatment for NB, the proposed studies will pave the way for future clinical evaluation of PMAT as a prognostic factor in tumor disposition and response to 131I-mIBG therapy.
Personnel
Wang, Joanne, Principal Investigator, Professor, PHARMACEUTICS • Zhang, Yuchen, Other, Senior Fellow, PHARMACEUTICS • Hu, Tao, Other, Senior Fellow, PHARMACEUTICS • Prasad, Bhagwat, Co-Investigator, Asst Professor Without Tenure, PHARMACEUTICS • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
PBPK prediction of ontogeny mediated alteration in hepatic drug elimination.
PRASAD, BHAGWAT , Pharmaceutics
Award Date: 05/25/2018
Sponsor: National Institute of Child Health and Human Development (NICHD) Amount: $31525
Abstract
With respect to drug disposition, children (especially neonates and infants) are different than the adults. Therefore it is not appropriate to select dosing regimen for this special population based on empirical scaling (e.g., based on body weight) of the adult dose. This issue becomes more significant as it is not always possible to establish safety and efficacy of drugs in the children at clinic due to logistical, ethical, safety and medico-legal concerns. For instance, out of 399 prescribed drugs to neonates/infants between 1997-2010, only 28 drugs were studied for the safety and/or efficacy. Thus, it is imperative that novel alternative approaches are developed to predict safe and efficacious dosing regimens for children. One such approach is to integrate age-dependent physiological parameters with drug specific parameters (e.g., in vitro enzyme/transport kinetic data) to develop a pediatric physiologically based pharmacokinetic (pPBPK) model. Once validated, such fully mechanistic pPBPK model can be generalized for any drug. However, the biggest hurdle in developing such models for children are the lack of absolute ontogeny data on the proteins that are related to drug disposition, i.e,, drug metabolizing enzymes (DMEs) and transporters. It is known that developmental pattern exists in the expression of major hepatic DMEs, but the available data are either qualitative/semi-quantitative or completely missing for most of the DMEs/transporters. Therefore, as a first step towards rectifying this gap in knowledge we propose to quantify the hepatic expression of DMEs and transporters in our unique pediatric livers (n=220) and compare this expression with that in adults. We will use selective and robust multiple reaction monitoring (MRM) proteomic approach to quantify these proteins. Once the age-dependent protein abundance data are available, these data can be integrated with in vitro kinetics and other developmental (physiological) information to construct a pPBPK models. Such rationally designed models can be validated using available clinical data on the model compounds, and then generalized to drugs that are eliminated by these mechanisms in the liver. Because mechanistic pPBPK models can delineate fractional role of individual metabolic/transport pathways in drug disposition, such mechanistic tools are also capable of accurately predicting drug-drug interactions (DDIs) and pharmacogenetic variability mediated by these pathways. Hence, this proposal addresses the mechanisms of hepatic drug disposition in neonates to adolescents. The pPBPK model generated in this study will be of enormous value with respect to child health as these will be important to assess the risk associated with the first use of drugs (or other xenobiotics) in children (including neonates/infants, where the ontogeny matters most).
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor, PHARMACEUTICS • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Zhang, Hae Young, Other, PREDOCTORAL RESEARCH ASSOCIATE 2, PCEUT - PRASAD L, PHARMACEUTICS • Chapa, Revathi, Other, RESEARCH SCIENTIST/ENGINEER - ASSISTANT, PCEUT - P, PHARMACEUTICS • Vrana, Marc A, Other, Predoctoral Research Associate 2, PHARMACEUTICS • Bhatt, Deepak Kumar, Other, Senior Fellow, PHARMACEUTICS • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Chau, Alvin, Budget Contact, Budget/fiscal Analyst Lead, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Gaps In Care -- NACDS Foundation.
Bacci, Jennifer Lynn , Department Of Pharmacy
Award Date: 05/22/2018
Sponsor: National Association of Chain Drug Stores (NACDS) Foundation Amount: $624446
Abstract
Given the significant gap in statin care that remains in patients with diabetes, we propose a two phased study to investigate closing this gap in care using an innovative community pharmacist-led model. An observational study will be conducted in phase 1 to investigate closing this gap in diabetes care using an innovative community pharmacist-led model, which includes proactive population health promotion and pharmacist initiated and managed statin therapy through a CPA. The primary objectives of the phase I observational intervention study are to compare the impact of usual care (control) and CPA and population health promotion (intervention) models on the change in (1) percent of pharmacy population with diabetes initiated on statin therapy and (2) patient adherence and persistence to statin therapy. The secondary objectives of this study are to assess pharmacy staff adoption of and fidelity to the clinical intervention. In phase II, a longer term outcomes analysis will be conducted to retrospectively assess the impact of the intervention on overall population health. The objectives of the phase II retrospective analysis are to evaluate (1) total health care costs and (2) coronary and atherosclerotic events of patients who received the innovative community-pharmacist led intervention.
Personnel
Bacci, Jennifer Lynn, Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • Gray, Shelly L., Co-Investigator, Professor, DEPARTMENT OF PHARMACY • Bansal, Aasthaa, Co-Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Hansen, Ryan, Co-Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Marcum, Zachary, Co-Investigator, Asst Professor Without Tenure, DEPARTMENT OF PHARMACY • Odegard, Peggy Soule, Multiple PI, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Fellowship Program in Pharmacoeconomics (Kim).
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 05/14/2018
Sponsor: Allergan, Inc. Amount: $214428
Abstract
Graduate Fellowship In Pharmacoeconomics in Health Systems/Managed Care Master of Science (M.S.) In Pharmaceutical SciencesArea of emphasis: Pharmaceutical Economics and Outcomes Research
Personnel
Devine, Emily E., Principal Investigator, Assoc Professor Without Tenure, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Dept Of Pharmacy, eGC1 Preparer
Fellowship Program in Pharmacoeconomics (Ta).
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 05/14/2018
Sponsor: Allergan, Inc. Amount: $214428
Abstract
Graduate Fellowship In Pharmacoeconomics in Health Systems/Managed Care Master of Science (M.S.) In Pharmaceutical SciencesArea of emphasis: Pharmaceutical Economics and Outcomes Research
Personnel
Devine, Emily E., Principal Investigator, Assoc Professor Without Tenure, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Dept Of Pharmacy, eGC1 Preparer
Impact of Cannabis on Inflammation and Viral Persistence in Treated HIV/SIV.
KLATT, NICHOLE , Pharmaceutics
Award Date: 05/11/2018
Sponsor: National Institute on Drug Abuse (NIDA) Amount: $89000
Abstract
With 35 million HIV-infected individuals worldwide, the challenge to improve health in these individuals is vast. Antiretroviral therapy (ART) suppresses HIV replication, which prevents AIDS and reduces overall mortality,however ART does not fully restore health. Indeed, despite sustained suppression of viremia, individuals cannot discontinue ART as residual HIV persists, and virus rebound is inevitable if ART is discontinued. Thisresidual HIV reservoir is associated with ongoing inflammation. Cannabis is a widely used drug in the United States, and derivatives of cannabis such as cannabinoids are commonly used in treatment of nausea and cachexia in severe conditions such as cancer. Several studies have demonstrated that cannabinoids have thepropensity to alter immune responses and decrease inflammation in vivo. We hypothesize that cannabis usein the context of ART-treated HIV infection may decrease inflammation and the persistent HIV reservoir. Here,we provocatively propose to test this hypothesis in humans by measuring inflammation, immunity, and the HIVreservoir from blood and gastrointestinal (GI) tissues from HIV-infected individuals who report using cannabisdaily compared to those reporting no drug use. Furthermore, we will assess mechanisms of cannabinoid antiinflammatoryactivity ex-vivo using cannabinoid receptor agonists in co-cultures. In addition, we will exploit thenon-human primate model of SIV infection to test causality of this unconventional idea, by treating ARTtreated,SIV infected macaques with cannabinoids to assess the effects on SIV reservoir and inflammation. With an outstanding team of researchers, we will assess the following: (i.) Global systems biology, includingspecies-specific transcriptional analysis and bioinformatics; (ii.) The HIV and SIV reservoir using novel assaysto measure integrated, total and inducible virus; (iii.) Inflammation and immunophenotype of immune cellsubsets; (iv.) Systemic microbial translocation and GI tract barrier integrity; and (v.) drug levels and kinetics inblood and GI tract. We believe these proposed studies will be integral to better understanding facetsassociated with the HIV reservoir and may provide a novel therapeutic approach, exploiting a drug of abuse,towards development of an HIV cure.
Personnel
Klatt, Nichole, Principal Investigator, Asst Professor Without Tenure, PHARMACEUTICS • Gustin, Andrew T., Other, PREDOCTORAL RESEARCH ASSOCIATE 2, School of Pharma, PHARMACEUTICS • Appelbe, Oliver K, Other, Research Scientist Engineer 3, PHARMACEUTICS • Helgeson, Eric J, Other, Registered Nurse 1 - Research, DEPARTMENT OF MEDICINE • Padullo, Emilda M, Other, Program Operations Specialist, DEPARTMENT OF MEDICINE • Coronado, Ernesto, Other, Research Scientist/engineer 1, PHARMACEUTICS • Fernandez, Frank C., Other, Senior Computer Specialist, IMMUNOLOGY SLU • Cheu, Ryan K, Other, Predoctoral Research Associate 2, PHARMACEUTICS • Jonsson, Christine Anne, Other, Research Consultant, DEPARTMENT OF MEDICINE • Storey, Sheryl S., Other, Health Care Specialist, DEPARTMENT OF MEDICINE • Kirkwood, Jay, Other, Research Scientist/engineer 2, PHARMACEUTICS • Isoherranen, Nina, Co-Investigator, Associate Professor, PHARMACEUTICS • Collier, Ann C, Co-Investigator, Professor Without Tenure, DEPARTMENT OF MEDICINE • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
University of Washington/Pfizer Post-Doctoral Traineeship award in economic evaluation, drug policy, and outcomes research.
GARRISON, LOUIS P , Department Of Pharmacy
Award Date: 05/11/2018
Sponsor: Pfizer US Pharmaceuticals Group Amount: $259706
Abstract
Pfizer shall provide the University of Washington Pharmaceutical Outcomes Research and Policy Program (PORPP) Post-Doctoral Traineeship award in economic evaluation, drug policy, and outcomes research.
Personnel
Garrison, Louis P, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Resistance Selection Potential of the Long Acting Lipoglycopeptides Dalbavancin and Oritavancin.
Werth, Brian , Department Of Pharmacy
Award Date: 05/10/2018
Sponsor: National Institutes of Health (NIH) Amount: $233125
Abstract
Dalbavancin and oritavancin are long-acting antimicrobials related to vancomycin that can be given as single dose treatments for methicillin-resistant Staphylococcus aureus (MRSA) infections, preventing the need for hospitalization. Our interdisciplinary team proposes to simulate average clinical exposures of dalbavancin and oritavancin in an in vitro model to determine the risk of these drugs to select for resistance to themselves and cross-resistance to vancomycin and daptomycin. Furthermore, we will characterize the resistance mechanisms using a novel and comprehensive lipidomic technique coupled with genome sequencing and biophysical methods.
Personnel
Werth, Brian, Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • Xu, Libin, Co-Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Salipante, Stephen, Co-Investigator, Asst Professor Without Tenure, LAB MEDICINE • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY
Supplement - Natural Product-Drug Interaction Research: The Roadmap to Best Practices.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 05/09/2018
Sponsor: Washington State University (WSU) Amount: $152751
Abstract
This administrative supplement seeks funding to conduct mechanistic in vitro studies of a high priority NP that poses a potential risk for clinically relevant NPDIs. As detailed in the U54 Center’s Research Performance Progress Report (RPPR) for Years 1 and 2, the Pharmacology Core developed a systematic approach to select four high priority NPs to study as precipitants of NPDIs. The final selected priority NPs included green tea, cannabinoids, licorice and goldenseal. Of these NPs, green tea was the first to be advanced to an Interaction Project followed by golden seal, and we now seek funding to evaluate the role of cannabinoids as perpetrators of drug interactions mediated through CYP enzymes, following oral consumption of marijuana products. Marijuana extract and its individual components have been used to treat (or self-treat) pain, nausea, loss of appetite, childhood epilepsy and researchers continue to explore possible uses for treating other medical conditions such as multiple sclerosis, seizures, AIDS, mental problems, substance-use disorders etc. Currently, twenty-nine states and the District of Columbia have legalized the use of marijuana in some form for medicinal and/or recreational purposes. However, there is a significant gap in our understanding of the potential of these cannabinoids to cause detrimental interactions with commonly used prescription drugs in humans. Hence, this funding is requested to conduct mechanistic in vitro studies evaluating the inhibitory potential of cannabinoids, when consumed orally, towards major CYP enzymes responsible for extensive metabolism of xenobiotics such as CYP3A, CYP2D6, CYP2C9 and CYP2C19.
Personnel
Unadkat, Jashvant D, Principal Investigator, Professor, PHARMACEUTICS • Maharao, Neha, Other, Senior Fellow, PHARMACEUTICS • Thummel, Kenneth E., Multiple PI, Professor, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Modulation of drug transport at the renal proximal tubule by uremic solutes – implications in chronic kidney disease.
YEUNG, CATHERINE , Department Of Pharmacy
Award Date: 05/08/2018
Sponsor: National Institutes of Health (NIH) Amount: $291748
Abstract
Dose adjustment of renally cleared drugs in patients with chronic kidney diseases (CKD) is currently based on serum creatinine concentration, a biomarker of glomerular filtration (GFR). Despite dose reduction, adverse drug reactions remain extremely prevalent in CKD patients. Often, observed changes in drug exposure do not follow predictions based on the decline in creatinine clearance (CLcr), as exemplified by penciclovir (PEN) and tenofovir (TEN). We assert that the primary cause of suboptimal drug dosing in patients with CKD is the failure of estimated CLcr to accurately reflect the functional decline of renal tubule secretory function in CKD patients, and that drugs cleared primaily by tubular secretion (vs filtration), are subject to further compromise in clearance due to inhibition of secretion by accumulating uremic solutes. Renal tubular secretion requires coordinated uptake transport at the basolateral membrane and efflux transport at the apical membrane of the proximal tubular epithelium. In vitro studies have established that accumulating uremic solutes such as hippuric acid (HA), indoxyl sulfate (IS), p-cresol sulfate (pCS), and trimethylamine N-oxide (TMAO), inhibit uptake OAT transporters. Our preliminary data suggests that these endogenous compounds also impact apical efflux transporters. We hypothesize that 1) both uptake and efflux transport proteins in the proximal tubule are inhibited by accumulating uremic solutes (HA, IS, pCS, TMAO) in individuals with CKD, and 2) inhibition of transporters by endogenous uremic solutes constitutes the principal cause of the complex nonlinear relationship between renal drug clearance and CLcr, and leads to intracellular accumulation of potential nephrotoxins.These hypotheses will be investigated using PEN and TEN as representative tubular drug transport substrates exhibiting a greater decline of renal drug clearance in CKD than that predicted by estimated CLcr. Oseltamivir carboxylate (OST) will serve as a comparative control, whose renal clearance does follow prediction by CLcr.In order to characterize the mechanisms by which uremic solutes alter tubular transporter protein function and potentiate tubular toxicity, we will use existing transfected cell technology coupled with an innovative three-dimensional, microphysiological, primary cell culture model that will allow, for the first time, dynamic measurement of transepithelial flux and real-time monitoring intracellular accumulation of model substrates penciclovir, tenofovir, and oseltamivir carboxylate. A concurrent clinical study will evaluate the same drugs in healthy subjects and patients with stage 3 or 4 chronic kidney disease. Successful completion of this innovative research program will provide in-depth insight into mechanisms that regulate tubular clearance function in the disease milieu which will lead to fundamental paradigm change in our clinical approach to managing drug dosing in CKD based upon a combination of filtration, tubular secretion, and uremic biomarkers.
Personnel
Yeung, Catherine, Principal Investigator, Acting Assistant Professor, DEPARTMENT OF PHARMACY • Zelnick, Leila, Key Personnel, Research Assistant Professor, DEPARTMENT OF MEDICINE • Unadkat, Jashvant D, Other, Professor, PHARMACEUTICS • Prasad, Bhagwat, Other, Asst Professor Without Tenure, PHARMACEUTICS • Kelly, Edward J, Other, Assoc Professor Without Tenure, PHARMACEUTICS • Himmelfarb, Jonathan, Co-Investigator, Professor, DEPARTMENT OF MEDICINE • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY
Optimizing Busulfan: Efficacy, Toxicity, and Pharmacometabolomics.
LIN, YVONNE S. , Pharmaceutics
Award Date: 05/04/2018
Sponsor: City of Hope National Medical Center Amount: $56160
Abstract
Dr. Lin will oversee the activities of the UW Pharmacokinetics Laboratory (PK Lab). The UW PK Lab staff will collect samples from clinical trial participants, quantitate those samples for select busulfan metabolites (i.e., tetrahydrothiophenium ion (THT+), THT+ 1-oxide, sulfolane, and 3-hydroxysulfolane) and communicate those results to the Dr. McCune at City of Hope and Dr. Baker at Fred Hutch.
Personnel
Lin, Yvonne S., Principal Investigator, Associate Professor, PHARMACEUTICS • Phillips, Brian, Other, Research Scientist/engineer 3, PHARMACEUTICS • Shireman, Laura M., Other, Research Coordinator, PHARMACEUTICS • Men, Alex J, Other, Student Assistant, PHARMACEUTICS • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, Grants And Contracts Manager/specialist, PHARMACEUTICS
Value of Information Methods for NHLBI Trials.
BASU, ANIRBAN , Department Of Pharmacy
Award Date: 04/25/2018
Sponsor: National Institutes of Health (NIH) Amount: $672732
Abstract
NHLBI faces major challenges in determining how best to allocate investment in randomized clinical trials (RCTs). Currently, there is no consistent mechanism to evaluate and compare proposed RCTs for NHLBI to best determine where to invest its limited dollars. Novel approaches in decision science can provide valuable information to enhance the RCT prioritization process at NHLBI. The overall objective of this project is to develop a comprehensive toolkit of pragmatic value of information (VOI) approaches and the corresponding software that can be readily used by clinical researchers and funders in order to assess the value of RCTs related to heart, lung and blood diseases. In addition, we will develop standardized tables that would report each component of these calculations for an RCT to improve transparency and communication of the results. Using these methods, one can estimate the value of a perfect study that would eliminate all uncertainty and be translated immediately. Such an estimate would provide an upper bound to the value of the RCT. Alternatively, one can estimate the value of an RCT with a proposed design that would partially eliminate uncertainty. In other applications, one can derive optimal sample sizes or compare alternative designs (e.g. adaptive versus traditional) for a proposed study. Such information and presentations of expected risk and value from different RCT investments can help NHLBI with a quantitative visualization of its investment portfolio and optimize that portfolio over time.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Veenstra, David, Key Personnel, Professor, DEPARTMENT OF PHARMACY • Probstfield, Jeffrey L, Co-Investigator, Professor Without Tenure, DEPARTMENT OF MEDICINE • Carlson, Joshua J., Co-Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • Branch, Kelley R., Co-Investigator, Assoc Professor Without Tenure, DEPARTMENT OF MEDICINE • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
GH-VAP Vaccine Structural Analysis.
LEE, KELLY K. , Medicinal Chemistry
Award Date: 04/17/2018
Sponsor: Bill and Melinda Gates Foundation Amount: $1035943
Abstract
We propose to collaborate with GH-VAP members in order to help advance infectious disease vaccine development towards a more rational, structure-based approach. The structural analysis methods we have developed through studies of the HIV Env (as a member of the BMGF CAVD) and influenza virus’ hemagglutinin glycoproteins are broadly applicable to a wide range of systems and are particularly powerful in providing structural information without the constraints of having to crystallize a protein. This opens the door to comparing protein and epitope structure in different constructs and from a range of variants with a goal of identifying how epitope structure changes in these different situations. The methods are also capable of examining antigen with flexible features such as loops and glycosylation intact, as well as in the presence of adjuvants or other components such as carrier molecules. An understanding of immunogen structures and their modes of recognition by antibodies provides a basis for iteratively altering the immunogen’s design in order to enhance the immune response.The primary biophysical and structural analytical methods we propose to use include hydrogen/deuterium-exchange mass spectrometry (HDX-MS), X-ray radical footprinting with mass spectrometry (XF-MS), small-angle X-ray scattering (SAXS), and electron microscopy (EM). These probe protein conformation and interactions with ligands such as receptors, antibodies and therapeutics. They also enable us to assess epitope stability and whether a protein is natively folded or misfolded. The approaches are amenable to a wide range of systems and sample conditions. In addition, quantitative biochemical and biophysical characterization of samples will be carried out in order to assess their compositional purity, conformational homogeneity, nativeness, and general physical properties such as stability, mass, monodispersity. Many of these techniques such as HDX-MS are frequently used by biotech and pharmaceutical companies to validate that biologic agents are properly folded as well as to assay for aggregation, degradation, and non-native structure.The specific analyses to be performed will depend on the particular collaboration, system of interest, and biological or translational question of interest. Some examples of questions include: 1) How does epitope presentation differ in different antigen constructs such as epitope scaffolds versus complete protein subunits or complexes, 2) How does antigen structure change in the presence of adjuvants, 3) What degree of conformational heterogeneity is observed in a sample, 4) How are antigens organized, distributed, and oriented on more complex vectors such as VSV, HBsAg, liposomes, and VLPs, 5) How do specific modifications to an antigen alter its structure, epitope presentation and stability?
Personnel
Lee, Kelly K., Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Guttman, Miklos, Key Personnel, Research Associate, MEDICINAL CHEMISTRY • Lee, Erik, Other, Budget/fiscal Analyst, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Lee, Erik, Budget Contact, Budget/fiscal Analyst, MEDICINAL CHEMISTRY • Lee, Erik, eGC1 Preparer, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY
Addressing gaps in clinically useful evidence on drug-drug interactions.
HORN, JOHN , Department Of Pharmacy
Award Date: 04/16/2018
Sponsor: University of Pittsburgh Amount: $2104
Abstract
Potential drug-drug interactions (PDDIs) represent a significant causality for adverse drug events. Unfortunately, PDDI information resources currently used by clinicians are incomplete and inaccurate. We propose a new PDDI knowledge representation paradigm that we hypothesize will yield more clinically relevant evidence than is currently possible which, in turn, will increase the completeness and accuracy of PDDI decision support tools and reduce risk of medication errors. Starting from our extensive body of preliminary work, we will build a framework that implements the new paradigm using statins and psychotropics (antidepressants and antipsychotics). We expect that the framework will be generalizable to PDDIs involving other drugs, including those predicted using methods from pharmacology and bioinformatics. We will advance three research aims while building the exemplar framework. The first research aim is to derive a new meta-data standard for representing PDDI knowledge that satisfies the information needs of clinicians working in different care settings. An information needs inquiry will result in clinical scenarios that will then inform, and later validate, the new standard. We will design the standard so that it reflects the best thinking of drug information system designers and the biomedical ontology community, extends existing national drug terminology efforts, and will have a high likelihood of widespread adoption. We will then combine the new standard with best practices for publishing Linked Data to create a Semantic Web knowledge base of statin and psychotropic PDDIs. The second research aim is to implement and evaluate a novel process for synthesizing PDDI evidence that combines natural language processing of structured drug product labels, evidence from publicly available drug information resources, and web-based manual curation. We hypothesize that the process will enable a more efficient synthesis of currently available PDDI evidence than is currently possible. The third research aim is to develop a general and accurate approach to dynamically enhancing the PDDI content provided in drug product labels. We hypothesize that the information limitations of product labels with respect to PDDIs can be overcome by building algorithms that link a computable representation of product label PDDI assertions to “assertion-evidence” networks that provide more complete and current drug information than the label alone. We will first develop the necessary data structures and knowledge content, and then explore innovative approaches to working with the enhanced product label information including a drug-information knowledge recommendation system and a patient-specific view for drug therapy decision support. The proposed work will contribute to public health by making more effective use of PDDI evidence, filling in important gaps in drug safety knowledge, and spurring innovations in drug information retrieval.
Personnel
Horn, John, Principal Investigator, Research Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Role of genetics on tobacco cessation in Alaska Native/American Indian Community.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 04/02/2018
Sponsor: Southcentral Foundation Amount: $110430
Abstract
Despite the considerable promise of PGX to guide tobacco cessation treatment and baseline characteristics noted in the Yupik population (higher CYP2A6 activity after controlling for genotype), several important questions remain about its implementation in a more heterogenous AN/AI community (e.g., cultural barriers, underserved and resource-limited settings).40 The goal of this proposal is to ensure that AN/AI communities of Alaska have sufficient information about PGX to determine its utility to guide tobacco cessation treatment by identifying potential genetic variations that could impact treatment outcomes, and determine how these tests could fit into the current Alaska Native Medical Center Tobacco Cessation Program.
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, PHARMACEUTICS • Trinidad, Susan B, Other, Research Scientist/engineer 4, BIOETHICS & HUMANITIES • Eng, Matthew N., Administrative Contact, Administrator, PHARMACEUTICS • Eng, Matthew N., Budget Contact, Administrator, PHARMACEUTICS • Eng, Matthew N., eGC1 Preparer, Administrator, PHARMACEUTICS • Eng, Matthew N., Budget Preparer, Administrator, PHARMACEUTICS
Effects of Retinoids on CYP2D6 Activity and Variability in Special Populations.
HEBERT, MARY F , Department Of Pharmacy
Award Date: 03/30/2018
Sponsor: National Institutes of Health (NIH) Amount: $520781
Abstract
CYP2D6, a key drug-metabolizing enzyme, is involved in the metabolism of ~20% of all drugs. We hypothesize that natural variation in retinoic acid concentrations and retinoid signaling in the liver regulate CYP2D6 expression and activity in humans, which in turn contributes to CYP2D6 pharmacokinetic variability and CYP2D6 induction during pregnancy. We will take a mechanistic approach and test the relationship between retinoid concentrations and CYP2D6 activity in 2 studies evaluating from the perspective of CYP2D6 induction during pregnancy, repression of induction with vitamin A administration and repression of normal CYP2D6 activity with 13-cis-retinoic acid (isotretinoin) in non-pregnant adolescent patients. Pregnant and adolescent patients often require treatment for chronic conditions, which can include CYP2D6 substrates. After accounting for genetic variation, there is still a great deal of unaccounted variability in CYP2D6 activity in these special populations making clinical management challenging. Basic science studies suggest that retinoids play an important role in CYP2D6 regulation. Our objective is to understand the role of retinoids in CYP2D6 activity in pregnant, postpartum and adolescent patients and translate new laboratory findings into humans. Our Specific Aims are: Specific Aim 1. To determine if vitamin A administration decreases CYP2D6 activity during pregnancy. In this aim, we will evaluate the effect of vitamin A administration on pregnancy-induced CYP2D6 activity. This study will provide mechanistic understanding of CYP2D6 induction and variability during pregnancy as well as provide a potential clinical strategy for management of pregnant women that require CYP2D6 substrates.Specific Aim 2. To investigate if isotretinoin (13-cis-retinoic acid) administration decreases CYP2D6 activity in adolescent patients. In this aim, we will conduct a drug-drug interaction study evaluating the effects of 13-cis-retinoic acid on non-induced CYP2D6 activity in adolescent patients. Secondary analysis will evaluate the relationship between retinoid concentrations and CYP2D6 activity in these special populations. In both Specific Aims we will utilize dextromethorphan as our CYP2D6 probe substrate. Through these complementary aims, we will be the first to conduct mechanistic testing of endogenous regulation of CYP2D6 activity in humans. The results could overcome a critical barrier to safe and effective administration of CYP2D6 substrates in adolescent and pregnant patients. Based on our compelling preliminary data, we expect to identify a novel mechanism of CYP2D6 regulation in humans and a potential management strategy for CYP2D6 induction and variability during pregnancy, with the intention of improving safety and efficacy of medications for these vulnerable patients. This work is critical for the provision of individualized therapy and along with genetics, the first step in development of an endogenous biomarker for CYP2D6 activity.
Personnel
Hebert, Mary F, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Easterling, Thomas R, Key Personnel, Professor Without Tenure, OBGYN/ADMIN • Isoherranen, Nina, Key Personnel, Associate Professor, PHARMACEUTICS • Vary, James, Key Personnel, Asst Professor Without Tenure, DEPARTMENT OF MEDICINE • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Characterizing the broad antibody response to HIV superinfection.
Lee, Kelly K. , Medicinal Chemistry
Award Date: 03/29/2018
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $109245
Abstract
A collaborative effort between the UW Lee lab and Fred Hutchinson Cancer Research Center lab’s led by Dr. Julie Overbaugh and colleagues, Drs. Jesse Bloom and Frederick Matsen will apply state-of-the-art structural, biophysical, and evolutionary analytical methods to understand the development of virus neutralization breadth in the context of HIV superinfection.
Personnel
Lee, Kelly K., Principal Investigator, Associate Professor, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY • Lee, Erik, Budget Contact, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
Screening of Investigational Compounds to Treat, Modify or Prevent Epilepsy for the NINDS Epilepsy Therapy Screening Program (ETSP).
WHITE, HAROLD STEVE , Department Of Pharmacy
Award Date: 03/16/2018
Sponsor: University of Utah Amount: $154196
Abstract
The systemic kainic acid (KA)-induced status epilepticus (SE) model in rats is an etiologically-relevant animal model of epileptogenesis. All of the clinical characteristics observed in human patients with temporal lobe epilepsy (TLE) are also observed in the rat systemic KA model of SE and TLE. Moreover, the systemic low-dose KA paradigm is ideally suited for preclinical drug screening studies to evaluate the long-term process of epileptogenesis. As a first attempt to identify novel and potentially efficacious antiepileptogenic agents, it is necessary to define whether administration of the investigational compound during the SE insult or immediately after (e.g. during the latent period) can first modify presentation and severity of spontaneous recurrent seizures, as well as attendant comorbidities, in the rat KA-SE model of epileptogenesis. The goal of the proposed studies is to determine whether administration of promising investigational anticonvulsant compounds can also modify or attenuate the presentation of spontaneous recurrent seizures days to weeks after SE, as well as modify the SE-induced behavioral deficits associated with TLE.
Personnel
White, Harold Steve, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Haliski, Melissa, Key Personnel, Research Scientist/engineer-senior, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
PBPK prediction of ontogeny mediated alteration in hepatic drug elimination.
PRASAD, BHAGWAT , Pharmaceutics
Award Date: 03/15/2018
Sponsor: National Institute of Child Health and Human Development (NICHD) Amount: $283717
Abstract
With respect to drug disposition, children (especially neonates and infants) are different than the adults. Therefore it is not appropriate to select dosing regimen for this special population based on empirical scaling (e.g., based on body weight) of the adult dose. This issue becomes more significant as it is not always possible to establish safety and efficacy of drugs in the children at clinic due to logistical, ethical, safety and medico-legal concerns. For instance, out of 399 prescribed drugs to neonates/infants between 1997-2010, only 28 drugs were studied for the safety and/or efficacy. Thus, it is imperative that novel alternative approaches are developed to predict safe and efficacious dosing regimens for children. One such approach is to integrate age-dependent physiological parameters with drug specific parameters (e.g., in vitro enzyme/transport kinetic data) to develop a pediatric physiologically based pharmacokinetic (pPBPK) model. Once validated, such fully mechanistic pPBPK model can be generalized for any drug. However, the biggest hurdle in developing such models for children are the lack of absolute ontogeny data on the proteins that are related to drug disposition, i.e,, drug metabolizing enzymes (DMEs) and transporters. It is known that developmental pattern exists in the expression of major hepatic DMEs, but the available data are either qualitative/semi-quantitative or completely missing for most of the DMEs/transporters. Therefore, as a first step towards rectifying this gap in knowledge we propose to quantify the hepatic expression of DMEs and transporters in our unique pediatric livers (n=220) and compare this expression with that in adults. We will use selective and robust multiple reaction monitoring (MRM) proteomic approach to quantify these proteins. Once the age-dependent protein abundance data are available, these data can be integrated with in vitro kinetics and other developmental (physiological) information to construct a pPBPK models. Such rationally designed models can be validated using available clinical data on the model compounds, and then generalized to drugs that are eliminated by these mechanisms in the liver. Because mechanistic pPBPK models can delineate fractional role of individual metabolic/transport pathways in drug disposition, such mechanistic tools are also capable of accurately predicting drug-drug interactions (DDIs) and pharmacogenetic variability mediated by these pathways. Hence, this proposal addresses the mechanisms of hepatic drug disposition in neonates to adolescents. The pPBPK model generated in this study will be of enormous value with respect to child health as these will be important to assess the risk associated with the first use of drugs (or other xenobiotics) in children (including neonates/infants, where the ontogeny matters most).
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor, PHARMACEUTICS • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Zhang, Hae Young, Other, PREDOCTORAL RESEARCH ASSOCIATE 2, PCEUT - PRASAD L, PHARMACEUTICS • Chapa, Revathi, Other, RESEARCH SCIENTIST/ENGINEER - ASSISTANT, PCEUT - P, PHARMACEUTICS • Vrana, Marc A, Other, Predoctoral Research Associate 2, PHARMACEUTICS • Bhatt, Deepak Kumar, Other, Senior Fellow, PHARMACEUTICS • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Chau, Alvin, Budget Contact, Budget/fiscal Analyst Lead, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
CRASH OSA.
HANSEN, RYAN , Department Of Pharmacy
Award Date: 03/14/2018
Sponsor: Jazz Pharmaceuticals Amount: $401681
Abstract
Obstructive sleep apnea (OSA) is a common chronic condition, affecting about 24% of men and 9% of women aged 30-60 years and 2-4% of all adults. OSA that is characterized by recurrent airway obstruction during sleep, leading to sleep fragmentation and sleepiness,. Many OSA patients experience excessive sleepiness, which may increase a patient’s risk of an accident or injury, such as motor vehicle accidents. The objectives of this study are to update existing evidence on the risk of motor vehicle accidents among patients with OSA and to evaluate the feasibility of identifying specific clinical parameters, including sleepiness measures, from electronic medical records using natural language processing.
Personnel
Hansen, Ryan, Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY
Exploring methods to improve utility adjustment in cost-effectiveness models and their impact on model outcomes.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 03/14/2018
Sponsor: PhRMA Foundation Amount: $100000
Abstract
Our research project would be an exploration into the effect of proposed methodologies that address disability and distribution issues on economic model outcomes. This project would bring together theoretical work on improving the QALY with established health economic models for Multiple Myeloma, Non-small cell lung cancer, Atopic Dermatitis, Multiple Sclerosis, Asthma, and Rheumatoid arthritis in order to better understand the impact of proposed methodological changes on cost-effectiveness outcomes within and across models.
Personnel
Carlson, Joshua J., Principal Investigator, Associate Professor, DEPARTMENT OF PHARMACY • Brouwer, Elizabeth D, Key Personnel, Predoctoral Research Associate 1, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY
Defining the Infant Immune Response to HIV.
LEE, KELLY K. , Medicinal Chemistry
Award Date: 03/12/2018
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $141741
Abstract
A major hurdle to developing a protective HIV vaccine is our inability to define a pathway to generate protective neutralizing antibodies. A recent study by our group showed that infants make notably broad and potent HIV neutralizing antibody responses, and do so relatively quickly. We propose to study how they accomplish this so that this information can be used help define more promising vaccine approaches.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Improving Access and Reducing Financial Burden for Patients on Specialty Drugs.
Basu, Anirban , Department Of Pharmacy
Award Date: 03/06/2018
Sponsor: Robert Wood Johnson Foundation Amount: $149900
Abstract
TBA
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
BMT CTN Ancillary Cost Effectiveness Analysis.
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 03/01/2018
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $12012
Abstract
Dr. Bansal will provide her statistical expertise to all aspects of the planned analyses including statistical data quality management, analysis of missing data, the most appropriate method to address missing data and subsequent missing data sensitivity analyses. Finally, Dr. Bansal will contribute her expertise to the preparation of reports and manuscripts.
Personnel
Bansal, Aasthaa, Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY _x000D_Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY _x000D_Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY _x000D_Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY _x000D_
Novel Systemically-Active Galanin Analogs for the Treatment of Pain.
WHITE, HAROLD STEVE , Department Of Pharmacy
Award Date: 02/22/2018
Sponsor: US Department of Defense (DOD) Amount: $1282161
Abstract
Transfer of a DOD Grant from the University of Utah
Personnel
White, Harold Steve, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Ehlers, Sellyna A, eGC1 Preparer, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY
Effects of Informal Care for persons with Alzheimer's Disease and related dementias.
Basu, Anirban , Department Of Pharmacy
Award Date: 02/21/2018
Sponsor: University of Pennsylvania Amount: $54476
Abstract
Dr Basu’s work has focused on estimating individual treatment effects. He will work with Dr. Coe and her research team to applying these methods in a new, very policy relevant domain of the interaction between formal and informal care among the elderly.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
A Pragmatic Trial to Improve Colony Stimulating Factor Use in Cancer.
SULLIVAN, SEAN , Department Of Pharmacy
Award Date: 02/16/2018
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $88144
Abstract
Pragmatic Clinical Studies and Large Simple Trials to Evaluate Patient-Centered Outcomes-- UW will participate as a subrecipient to the Fred Hutch.
Personnel
Sullivan, Sean, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Bansal, Aasthaa, Key Personnel, Research Assistant Professor, DEPARTMENT OF PHARMACY • McCune, Jeannine S., Key Personnel, Professor, DEPARTMENT OF PHARMACY • Goulart, Bernardo Haddock, Key Personnel, Asst Professor Without Tenure, DEPARTMENT OF MEDICINE • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Ehlers, Sellyna A, eGC1 Preparer, Program Operations Specialist, DEPARTMENT OF PHARMACY
Impact of Cannabis on Inflammation and Viral Persistence in Treated HIV/SIV.
KLATT, NICHOLE , Pharmaceutics
Award Date: 02/09/2018
Sponsor: National Institute on Drug Abuse (NIDA) Amount: $801000
Abstract
With 35 million HIV-infected individuals worldwide, the challenge to improve health in these individuals is vast.Antiretroviral therapy (ART) suppresses HIV replication, which prevents AIDS and reduces overall mortality,however ART does not fully restore health. Indeed, despite sustained suppression of viremia, individualscannot discontinue ART as residual HIV persists, and virus rebound is inevitable if ART is discontinued. Thisresidual HIV reservoir is associated with ongoing inflammation. Cannabis is a widely used drug in the UnitedStates, and derivatives of cannabis such as cannabinoids are commonly used in treatment of nausea andcachexia in severe conditions such as cancer. Several studies have demonstrated that cannabinoids have thepropensity to alter immune responses and decrease inflammation in vivo. We hypothesize that cannabis usein the context of ART-treated HIV infection may decrease inflammation and the persistent HIV reservoir. Here,we provocatively propose to test this hypothesis in humans by measuring inflammation, immunity, and the HIVreservoir from blood and gastrointestinal (GI) tissues from HIV-infected individuals who report using cannabisdaily compared to those reporting no drug use. Furthermore, we will assess mechanisms of cannabinoid antiinflammatoryactivity ex-vivo using cannabinoid receptor agonists in co-cultures. In addition, we will exploit thenon-human primate model of SIV infection to test causality of this unconventional idea, by treating ARTtreated,SIV infected macaques with cannabinoids to assess the effects on SIV reservoir and inflammation.With an outstanding team of researchers, we will assess the following: (i.) Global systems biology, includingspecies-specific transcriptional analysis and bioinformatics; (ii.) The HIV and SIV reservoir using novel assaysto measure integrated, total and inducible virus; (iii.) Inflammation and immunophenotype of immune cellsubsets; (iv.) Systemic microbial translocation and GI tract barrier integrity; and (v.) drug levels and kinetics inblood and GI tract. We believe these proposed studies will be integral to better understanding facetsassociated with the HIV reservoir and may provide a novel therapeutic approach, exploiting a drug of abuse,towards development of an HIV cure.
Personnel
Principal Investigator, Asst Professor Without Tenure, PHARMACEUTICS, klattnr@uw.edu • Other, PREDOCTORAL RESEARCH ASSOCIATE 2, School of Pharma, PHARMACEUTICS, atgustin@uw.edu • Other, Research Scientist Engineer 3, PHARMACEUTICS, oappelbe@uw.edu • Other, Registered Nurse 1 - Research, DEPARTMENT OF MEDICINE, ehelgeso@u.washington.edu • Other, Program Operations Specialist, DEPARTMENT OF MEDICINE, melvis@u.washington.edu • Other, Research Scientist/engineer 1, PHARMACEUTICS, • Other, Senior Computer Specialist, IMMUNOLOGY SLU, fcf@uw.edu • Other, Predoctoral Research Associate 2, PHARMACEUTICS, • Other, Research Consultant, DEPARTMENT OF MEDICINE, cjonsson@u.washington.edu • Other, Health Care Specialist, DEPARTMENT OF MEDICINE, sstorey@u.washington.edu • Other, Research Scientist/engineer 2, PHARMACEUTICS, • Co-Investigator, Associate Professor, PHARMACEUTICS, ni2@u.washington.edu • Co-Investigator, Professor Without Tenure, DEPARTMENT OF MEDICINE, acollier@u.washington.edu • Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS, royall@uw.edu • Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS, royall@uw.edu • eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu
Population-based Interventions to Improve Behavioral Health in a Tribal Healthcare System.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 02/02/2018
Sponsor: Southcentral Foundation Amount: $87172
Abstract
Dr. Thummel will be responsible for overseeing work by staff in the Clinical Pharmacokinetics Lab to quantify vitamin D (VitD) concentrations in plasma samples that will be collected in Specific Aim 2 (SA2) and SA3. He will also oversee genotyping of DNA samples from the same Aims, working closely with staff in the EDGE Functional Genomics lab. He will supervise Ms. Calamia and her efforts to quantify VitD metabolites. Dr. Thummel will work with Dr. Robinson and Dr. Timothy Thornton, PhD biostatistician to oversee the statistical analyses planned for SA2 and SA3 and work closely with all project investigators on the publication of research findings. He will also support Ms. Trinidad, a Research Scientist at the Department of Bioethics and Humanities. She will train Ms. Beans in qualitative research techniques, assist with analysis of data, and results dissemination; development of study management materials for Specific Aim 2, and lay dissemination materials for Specific Aims 1, 2, and 3.Dr. Kenneth Thummel, the Milo Gibaldi Endowed Professor and Chairman of the Department of Pharmaceutics in the UW School of Pharmacy and Adjunct Professor of Environmental Health Sciences in the School of Public Health, will provide scientific direction and oversight for career development and mentorship activities related to Specific Aim 1 including focused mentoring. Ms. Susan Trinidad will assist with manuscript writing and copy editing in Specific Aims 2 and 3, and will assist Dr. Hiratsuka’s SCF based team in the development of dissemination materials, and peer-review manuscripts. Additionally, Ms. Trinidad will travel to Anchorage annually to provide technical assistance in person.
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, PHARMACEUTICS _x000D_Thornton, Timothy A., Key Personnel, Associate Professor, BIOSTATISTICS _x000D_Trinidad, Susan B, Key Personnel, Research Scientist/engineer 4, BIOETHICS & HUMANITIES _x000D_Calamia, Justina C., Other, Research Scientist/engineer 2, PHARMACEUTICS _x000D_Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS _x000D_Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS _x000D_Royall, Frederick, eGC1 Preparer, Grants And Contracts Manager/specialist, PHARMACEUTICS
RPPR Year 1_Hu R01_A1 Prime Boost.
HU, SHIU-LOK , Pharmaceutics
Award Date: 01/31/2018
Sponsor: National Institutes of Health (NIH) Amount: $875225
Abstract
To date, the only vaccine trial (RV144) that has shown any protective efficacy against HIV acquisition is based on a poxvirus prime – protein boost immunization strategy. Although the efficacy achieved was modest (~31%), these findings provide a strong rationale to seek improvements for the prime-boost immunization approach and to gain better insight on the nature of the protective immunity achieved. Correlate studies of the RV144 trial indicated that antibodies against the hypervariable loops 1 and 2 (V1/V2) region of HIV envelope protein (Env) and high levels of antibody-dependent cellular cytotoxicity (ADCC) activities inversely correlated with the risk of HIV-1 acquisition. Neutralizing antibodies (Nabs) were generated, but were primarily against sensitive (“Tier 1”) isolates, with little or no activity against the more resistant (“Tier 2”) strains typical of circulating viruses. Thus, much of the current effort in HIV vaccine research aims to elicit Tier 2 Nabs and to improve the potency and the breadth of non-neutralizing antibody responses, including V1/V2 directed antibodies and antibodies that can mediate ADCC. Using a replication-competent poxvirus for priming and gp120 for boosting, we were able to induce Nab against heterologous Tier 2 viruses as well as cross-reactive V1/V2-specific antibodies and high levels of ADCC activities in rabbits. In this application, we propose to examine novel immunogens and immunization approaches to further enhance the breadth and potency of the Nab and non-Nab responses achieved and to determine if findings in rabbits can be translated to non-human primates. We hypothesize that by presenting the Env antigen in a native trimer form with the conserved CD4 binding site unmasked, we will enhance cross-reactive Nab, and by using polyvalent Env immunogens, we will amplify responses to conserved epitopes, while broadening strain-specific responses, including those directed to variable regions. The enhanced breadth and potency of both Nab and non-Nab responses, including V1/V2-directed antibodies and those that mediate antiviral effector functions, such as ADCC, will contribute to protection against challenge in a non-human primate model. The Specific Aims are: (1) To determine if trimeric Env, instead of monomeric gp120, when used as the boosting immunogen in a prime-boost regimen may improve the breadth or potency of Nab responses; (2) To determine if the ability of a highly conserved glycan (N197) to modulate Env immunogenicity is dependent on the use of trimeric Env, instead of monomeric gp120; (3) To determine if polyvalent, rather than monovalent Env, when used in a prime-boost immunization regimen, can improve the breadth and potency of Env-specific antibody responses; and (4) To examine if immunization regimens down-selected from the preceding studies in rabbits can be translated to macaques and if the immune responses generated can protect against SHIV challenge. If successful, insights obtained from these studies will inform the clinical development of vaccines and vaccine strategies that may be more effective than those used in RV144 to prevent HIV-1 acquisition in humans.
Personnel
Hu, Shiu-Lok, Principal Investigator, Professor, PHARMACEUTICS _x000D_Firpo, Patricia S., Other, RESEARCH SCIENTIST/ENGINEER-SENIOR, Hu Lab - PRIMA, REGIONAL PRIMATE CTR _x000D_Cleveland, Bradley R., Other, RESEARCH SCIENTIST/ENGINEER 3, PCEUT - HU LAB, PHARMACEUTICS _x000D_Guo, Wenjin, Other, RESEARCH SCIENTIST/ENGINEER 3, PCEUT - HU LAB, PHARMACEUTICS _x000D_Lee, Kelly K., Co-Investigator, Associate Professor, MEDICINAL CHEMISTRY _x000D_Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS _x000D_Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS_x000D_Diamond, Deborah L, eGC1 Preparer, RESEARCH MANAGER, PCEUT - ADMIN, PHARMACEUTICS
Targeting novel pathways to enhance gastrointestinal integrity during HIV infection.
KLATT, NICHOLE , Pharmaceutics
Award Date: 01/31/2018
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Amount: $324107
Abstract
The pathology of disease caused by HIV infection is complex and multifaceted. HIV infection results in a vicious cycle of mucosal damage, chronic inflammation and overall immunological dysfunction, which are closely associated with disease, and are not ameliorated with antiretroviral therapy (ART). This chronic inflammation is strongly associated with gastrointestinal (GI) mucosal barrier damage and microbial translocation, which also do not resolve completely with ART. Furthermore, mucosal dysfunction is associated with increased morbidities and mortality in HIV-infected individuals. Thus, it is imperative that novel therapeutic strategies aimed at enhancing mucosal function are developed. However, it is still unclear what pathways lead to damage to the GI tract during HIV infection, and thus a substantial hurdle for the development of targeted therapies. Here, our global hypothesis is that an inflammatory proteome comprised of neutrophil secretions in the GI tract is driven by microbiome dysbiosis, and is the mechanism underlying tight epithelial barrier disruption and mucosal dysfunction. We will test these hypotheses in HIV-infected individuals with high versus low disease pathogenesis profiles (measured by CD4/CD8 ratio), as well as in uninfected individuals, in the following aims: (I) We will assess whether an altered gastrointestinal proteome underlies mucosal dysfunction in HIV infection; (II) We will determine if neutrophil accumulation and dysfunction in the GI tract results in this inflammatory GI proteome; (III) We will assess whether the mechanism underlying neutrophil dysfunction and accumulation is HIV-associated microbiome dysbiosis. We will use novel data-driven modeling approaches to provide systems level insight of these complex relationships. Our ultimate goal is to define mechanisms and novel targets for therapeutic interventions by identifying pathways associated with mucosal inflammation and epithelial damage in HIV-infected individuals.
Personnel
Klatt, Nichole, Principal Investigator, Asst Professor Without Tenure, PHARMACEUTICS • Helgeson, Eric J., Other, Registered Nurse 1 - Research, DEPARTMENT OF MEDICINE • Padullo, Emilda M., Other, Program Operations Specialist, DEPARTMENT OF MEDICINE • Jonsson, Christine Anne, Other, Research Consultant, DEPARTMENT OF MEDICINE • Storey, Sheryl S., Other, Health Care Specialist, DEPARTMENT OF MEDICINE • Louella, Michael W., Other, Program Coordinator, DEPARTMENT OF MEDICINE • Collier, Ann C, Co-Investigator, Professor Without Tenure, DEPARTMENT OF MEDICINE • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Functional Dynamics of P-glycoprotein.
ATKINS, WILLIAM M. , Medicinal Chemistry
Award Date: 01/24/2018
Sponsor: National Institutes of Health (NIH) Amount: $268971
Abstract
This project aims to understand the mechanism of a protein, P-glycoprotein, that contributes to cancer cell drug resistance and the clearance and pharmacokinetics of most drugs. The mechanism by which P-glycoprotein (P-gp) recognizes and exports such a wide range of drugs is not known. P-gp utilizes the hydrolysis of ATP for the energy required to pump drugs out of cells but the coupling between ATP hydrolysis and drug export is not known. The major hypothesis of this proposal is that different drugs elicit different conformations of P-gp that differentially favor ATP hydrolysis. With a better understanding of P-gp mechanism, it will be possible to design P-gp inhibitors to improve the efficacy of anticancer drugs or to improve the pharmacokinetics of other drugs.
Personnel
Atkins, William M., Principal Investigator, Professor, MEDICINAL CHEMISTRY • Dabrowski, Michael J., Other, Research Scientist/engineer 2, MEDICINAL CHEMISTRY • Li, Jiarong Mavis, Other, Predoctoral Research Associate 2, MEDICINAL CHEMISTRY • Nath, Abhinav, Co-Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Lee, Erik, Budget Contact, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
Natural Product-Drug Interaction Research: The Roadmap to Best Practices.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 01/22/2018
Sponsor: Washington State University (WSU) Amount: $77550
Abstract
Administrative CoreThe Administrative Core under the parent grant has a two-fold responsibility. At the program level, the Administrative Core coordinates the basic administrative and financial services to the Cores and participating institutions. At the project level, the Administrative Core is charged with 1) supporting the oversight Steering Committee in monitoring and approving selection of the priority NPs and completion of the Statements of Work (SOWs) by the Pharmacology Core; 2) participating in the Interaction Project teams to monitor progress and the transfer of samples and data to the Analytical and Pharmacology Cores, respectively; 3) developing and disseminating the Recommended Approaches (RAs); and 4) coordinating with the Informatics Core to develop and maintain the web portal to allow public access to Best Practices and archived data from the Interaction Projects.The Administrative Core component of this subcontract supports the effort of Dr. Danny Shen (Co-I). Dr. Shen, who formerly was the PI of the U54 grant before he assumed semi-retirement in September of 2016, will mainly provide advice and counsel for the first three elements of the programmatic function of the Administrative Core, namely design and construction of the SOWs, execution of the Interaction Projects, and development of the RAs.Pharmacology CoreFor the remaining 3-year period of the parent grant, the Pharmacology Core has the principal responsibility of designing and guiding the implementing the Interaction Projects through the development of SOWs. The development path begins with a carefully orchestrated set of preclinical studies on selected natural product-drug interactions (NPDIs) and ends with a definitive assessment of the risk or safety of the NPDIs, or the need for further investigation. Using rigorous, predefined decision trees as guides, detailed SOWs for the selected NPDIs will be developed. These SOWs represent key deliverables of this Core and will be used subsequently to develop RAs for NPDI research.The Pharmacology Core component of this subcontract supports the efforts of Dr. Allan Rettie (Co-I) and Dr. Jashvant Unadkat (Co-I), two preeminent translational and clinical pharmacologist. The two Co-I will work with the PI of the parent grant, Dr. Mary Paine in developing the SOWs for the three selected priority natural products: green tea, goldenseal and cannabis. UW portion of the Pharmacology Core will conduct all the necessary preclinical studies for identifying potential drug interactions with cannabis extracts and its constituent cannabinoids. At present, the preclinical studies will largely consist of validated in vitro screening assays for known drug metabolizing enzymes and drug transporters. Bench support will be provided by a qualified postdoctoral fellow, Dr. Neha Maharao.Analytical CoreUnder the parent grant, the Analytical Core is charged with 1) characterizing the bioactive constituents of the priority natural products selected for the Interaction Projects, 2) synthesizing and supplying the purified bioactive constituents for preclinical studies on drug interaction potentials, and 3) supporting the analysis of samples generated from both the preclinical and human subject studies under the Interaction Projects.The Analytical Core component of this subcontract will focus on the third charge, mainly to provide the critical analytical support for the preclinical studies on standardized cannabis extracts obtained from National Institute on Drug Abuse (NIDA) in regards to their potential for modulating drug metabolizing enzymes and drug transporters. The analysis tasks will consist of development of sensitive and specific mass-spectrometry based assays for the cannabinoid constituents present in the cannabis extracts (i.e., the perpetrators) and the drug and/or metabolites of the probes used in the enzyme or transporter screens. All assays will be performed in our shared research resource PK Lab in the Department of Pharmaceutics.A secondary assignment for the UW component of the Analytical Core is to provide back-up support or overflow capacity in the analysis of biological samples (i.e., blood/plasma and urine) collected from human subject studies under the Interaction Projects. At present, the analyses are being handled by Dr. Mary Paine’s laboratory at WSU. UW PK Lab will provide back-up LC-MS/MS support on those occasions when the WSU LC-MS facility develops major instrumentation problems. The PK Lab will also handle overflow samples from WSU according well-defined Standard Operating Procedures (SOPs).
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, PHARMACEUTICS • Maharao, Neha, Other, Senior Fellow, PHARMACEUTICS • Phillips, Brian, Other, Research Scientist/engineer 3, PHARMACEUTICS • Shen, Danny D, Co-Investigator, Professor Emeritus, PHARMACEUTICS • Unadkat, Jashvant D, Co-Investigator, Professor, PHARMACEUTICS • Rettie, Allan E., Co-Investigator, Professor, MEDICINAL CHEMISTRY • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, Grants And Contracts Manager/specialist, PHARMACEUTICS
Impact of anticholinergic and dopamine receptor blocking drug exposure on Parkinson Disease trajectory and outcomes.
GRAY, SHELLY L. , Department Of Pharmacy
Award Date: 01/16/2018
Sponsor: University of Pennsylvania Amount: $29241
Abstract
This application will examine how anticholinergic and antidopaminergic medication exposure relate to measured outcomes in Parkinson disease populations. Dr. Gray will be involved in all aspects of the study including study design, analysis, interpretation of findings, and manuscript preparation. My primary responsibility is to provide guidance on the measurement of medication exposure from Medicare claims data. This will entail bi-monthly meetings over the course of the study period.
Personnel
Gray, Shelly L., Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY • Ehlers, Sellyna A, Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
PORPP-ICER 2018-19.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 01/10/2018
Sponsor: Institute for Clinical and Economic Review Amount: $577884
Abstract
The PoRPP Program will provide the following: •Collaborate with ICER on development and refinement of project scope and work streams and preferred reporting mechanisms;•Collaborate with ICER on model documentation;•Develop economic analyses in collaboration with ICER (up to five per year)oProgram would adhere to best practices in economic evaluation and include both cost-effectiveness and budget impact modeling of specific medical interventions of interest to the payer and healthcare policy community•Prepare draft and final written summaries and technical reports of the economic evaluations using agreed upon templates;•Attend and present at public meetings or webinars
Personnel
Carlson, Joshua J., Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY _x000D_Veenstra, David, Key Personnel, Professor, DEPARTMENT OF PHARMACY _x000D_Guzauskas, Greg, Other, Project Appointment - Overtime Exempt, DEPARTMENT OF PHARMACY _x000D_Basu, Anirban, Co-Investigator, Professor, DEPARTMENT OF PHARMACY _x000D_Weatherford, Sally, Administrative Contact, Administrator, DEPARTMENT OF PHARMACY _x000D_Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY _x000D_Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Mucosal mechanisms of altered HIV susceptibility in adolescents.
KLATT, NICHOLE , Pharmaceutics
Award Date: 01/08/2018
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) Amount: $681171
Abstract
Over 250,000 of HIV infections globally are in young women, signifying a significant burden for this population in the global epidemic. In areas such as sub-Saharan Africa, which has 70% of new global HIV infections, women aged 15-24 years have rates up to 8-fold higher than their male peers (UNAIDS 2011). Compared to their aged-matched male counterparts, they acquire HIV infection at least 5-7 years earlier1. In high-burden areas within South Africa, new infections are on the rise and alarmingly high women below the age of 20 years old, rising from 13% in 2007 to as high as 22% in 2013 (estimated adult prevalence rate of 16.7% for South Africa in 2012). This proposal is built upon several lines of novel unpublished and published evidence generated from our team about mucosal immunological determinants associated with increased HIV susceptibility. These include 1) Detailed mucosal epithelial barrier disruption signatures preceding and correlated with higher HIV infection outcome in the CAPRISA-004 trial (Burgener-preliminary data) and its association with younger women; 2) the link between these signatures and increased mucosal CD4+ T-cells which are targets for HIV (Burgener)19; 3) that adolescents have increased mucosal CD4+ T cells in the female genital tract (Klatt-preliminary data); 4) vaginal microbiome community groups contributing to increased HIV target cell activation7 and impaired wound healing (Klatt/Burgener- preliminary data); 5) initial HIV susceptible cellular targets within the female genital tract (Hope-prelim data). This project builds on novel data from our team which serve as avenues of investigation to understand the enhanced risk of HIV transmission in adolescent women and the foundation of this proposal. Therefore, based on our preliminary data and from others, we hypothesize that compared to adults, adolescents have 1) lower levels of protective mucosal protein barriers; 2) heightened levels of baseline inflammation in the genital tract; 2) lower levels of protective Lactobacillus species; 3) increased levels of genital tract immune cell homing markers; 4) increased density of HIV target cell in FGT tissue.
Personnel
Klatt, Nichole, Principal Investigator, ASSOCIATE PROFESSOR, Department of Pharmaceutics, PHARMACEUTICS • Miller, Charlene J, Key Personnel, RESEARCH SCIENTIST/ENGINEER 2, PCEUT - KLATT LAB, PHARMACEUTICS • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Monitoring and Evaluation Framework and Roadmap for Implementation.
STERGACHIS, ANDREAS S. , Department Of Pharmacy
Award Date: 01/02/2018
Sponsor: The Max Foundation Amount: $39987
Abstract
Cancer is a major burden of disease in low- and middle-income countries (LMICs) yet financial barriers limit access to life-saving oncology drugs. Medical donations help improve patient access to quality assured oncology drugs for people living in LMICs. Sound monitoring and evaluation (M & E) of medical donation programs can support program improvement and decision making as well as foster transparency of program processes and outcomes to management and to stakeholders. However, the type, scope and rigor of M & E for medical donation programs have been variable and outcomes are rarely evaluated and/or reported. Proposed is the development of a comprehensive M & E, framework and implementation plan for The Max Foundation Access Program. The Max Foundation Access Program is designed to improve global access to quality assured oncology drugs. Also proposed is assistance with designing and implementing practical methods and procedures for conducting outcomes and impact evaluations and dissemination of such knowledge.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Molecular basis of altered drug metabolism during pregnancy.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 12/21/2017
Sponsor: University of Illinois, Chicago Amount: $7750
Abstract
For the studies proposed in this application, in years 4 and 5 we will conduct all the retinoic acid, retinol, retinyl ester and RBP4 measurements in the human plasma and serum samples using our validated and sensitive liquid chromatography mass spectrometry methods to aid in determining the role of retinoids in altering CYP2D6 expression during pregnancy. We will be responsible for all sample preparation and LC-MS/MS analysis. We will also prepare the quantitative reports of the results generated from the above studies to facilitate publication of the results.
Personnel
Isoherranen, Nina, Principal Investigator, Associate Professor, Pharmaceutics • Kirkwood, Jay, Other, Research Scientist/engineer 2, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, Budget Contact, Grants and Contracts Manager/Specialist, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/Specialist, Pharmaceutics • Royall, Frederick, Budget Preparer, Grants and Contracts Manager/Specialist, Pharmaceutics
Competing Revision - Precision Medicine and Oral Anticoagulants.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 12/19/2017
Sponsor: National Institute of General Medical Sciences (NIGMS) Amount: $297702
Abstract
pending.
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, Pharmaceutics • Calamia, Justina C., Other, Research Scientist/engineer 2, Pharmaceutics • Thornton, Timothy A., Co-Investigator, Associate Professor, Biostatistics • Rettie, Allan E., Co-Investigator, Professor, Medicinal Chemistry • Veenstra, David, Co-Investigator, Professor, Department of Pharmacy • Prasad, Bhagwat, Co-Investigator, Asst Professor Without Tenure, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants And Contracts Manager/specialist, Pharmaceutics
Persistent modulation of microbiota to enhance HIV vaccination.
KLATT, NICHOLE , Pharmaceutics
Award Date: 12/19/2017
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) Amount: $886469
Abstract
Here we propose a novel HIV vaccination approach that uses persistent probiotic therapy as an adjuvant to enhance immunogenicity and protection induced by a potent combined vaccine strategy. Our vaccine consists of concurrently administered SIV (gag p55) and HIV (gp140) DNA + HIV gp140 trimer protein. Recent studies have provided evidence that combining DNA and protein for vaccination elicits increased vaccine specific cellular and humoral immunity, In addition, our preliminary studies provocatively demonstrated that probiotic treatment in SIV-uninfected macaques results in increased T follicular helper cells in lymph nodes, IgA expressing B cells in mucosal tissues, increased antigen presenting cells in mucosal tissues, and increased multifunctional T cells, as well as decreased proliferation and activation of CD4+ T cells. Thus, we hypothesize that combining the potent immunomodulatory effects of beneficial microbiota manipulation with a novel vaccine platform that should induce robust cellular and humoral immunity will result in unprecedented high levels of vaccine specific responses in both mucosal and systemic tissues, resulting in protection from rectal SHIV challenge.
Personnel
Klatt, Nichole, Principal Investigator, Asst Professor Without Tenure, Pharmaceutics • Manuzak, Jennifer, Other, Senior Fellow, Pharmaceutics • Fuller, Deborah, Co-Investigator, Assoc Professor Without Tenure, Microbiology • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics
The University of Washington, School of Pharmacy Research Affiliates Program on Transporters (UWRAPT).
UNADKAT, JASHVANT D , Pharmaceutics
Award Date: 12/13/2017
Sponsor: Pfizer, Inc. Amount: $60000
Abstract
The goal of this project is to establish a Research Affiliates Program at the UW within the School of Pharmacy. The RAP will bring together UW researchers and industry partners interested in furthering research to elucidate and quantify the role of transporters in the absorption, disposition, efficacy and toxicity of drugs..
Personnel
Unadkat, Jashvant, Principal Investigator, Professor, Pharmaceutics • Rogers, Catherine Cole, Other, Fiscal Specialist 1, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants and Contracts Manager/specialist, Pharmaceutics • Eng, Matthew N., Budget Contact, Administrator, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/specialist, Pharmaceutics • Chau, Alvin, Budget Preparer, Budget/fiscal Analyst Lead, Pharmaceutics
Estimating the Economic Impact of Pre-Diagnosis Health Care Resource Use in Patients with Infantile Spasms.
HANSEN, RYAN , Department Of Pharmacy
Award Date: 12/12/2017
Sponsor: Mallinckrodt, Inc. Amount: $59632
Abstract
Specific AimsThis study is comprised of three specific aims:1) Describe the healthcare resource use and treatment patterns of IS patients in the 90 days prior to the first IS diagnosis.2) Compare the 90-day pre-diagnosis resource use and treatment patterns of IS patients who receive Acthar to those who receive Sabril.3) Disseminate prior and current findings on the use of H.P. Acthar Gel in Neurologic Disorders in the form of two scientific manuscripts.
Personnel
Hansen, Ryan, Principal Investigator, Research Assistant Professor, Department of Pharmacy • Weatherford, Sally, Administrative Contact, Administrator, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, Pharm - A, Department of Pharmacy • Luetjen, Karen H., eGC1 Preparer, Grants And Contracts Manager/specialist, Pharm - A, Department of Pharmacy
Rational Integration of clinical SEquencing (RISE).
VEENSTRA, DAVID , Department Of Pharmacy
Award Date: 12/06/2017
Sponsor: Vanderbilt University Medical Center Amount: $186096
Abstract
The University of Washington subcontract will be directed by Dr. David Veenstra, who will be responsible for developing cost effectiveness models for genomic sequencing. Dr. Veenstra will have responsibility for all administrative and scientific activities conducted at University of Washington. He will oversee study personnel and will ensure completion of all study activities. Dr. Veenstra will supervise the work of the senior scientist and a graduate student research assistant.
Personnel
Veenstra, David, Principal Investigator, Professor, Department of Pharmacy • Weatherford, Sally, Administrative Contact, Administrator, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, Pharm - A, Department of Pharmacy • Ehlers, Sellyna A, eGC1 Preparer, Grants And Contracts Manager/specialist, Department of Pharmacy • Ehlers, Sellyna A, Budget Preparer, Grants And Contracts Manager/specialist, Department of Pharmacy
Effectiveness of Gastric Sleeve vs. Gastric Bypass for Cardiovascular Disease Y2.
BASU, ANIRBAN , Department Of Pharmacy
Award Date: 12/04/2017
Sponsor: Kaiser Permanente Amount: $207080
Abstract
Bariatric surgery is one of the most effective treatment strategies for weight loss in the severely obese. Currently, two operations constitute the majority of these procedures: Vertical Sleeve Gastrectomy (VSG), the newest restrictive procedure, in which only stomach size is reduced, and Roux-en-Y Gastric Bypass (RYGB), the ‘gold standard’ procedure, in which gastric capacity is similarly limited but with an additional modest bypass of a section of small intestine. From 2008-2011, there was a ~5-fold increase in use of VSG in North America (from 4% to 19%); in contrast, use of RYGB declined from 51% to 47%. If trends continue, VSG may comprise up to 50% or more of all bariatric procedures by 2020. The reasons for this dramatic shift in procedural preference are unknown, but it is likely due to the perception of surgeons that VSG and RYGB are at clinical equipoise, but VSG is easier to perform, less expensive, and has fewer complications. A clear evidence base to support these perceptions does not exist. Current clinical knowledge suffers from two major gaps. GAP 1: Very few studies have included many important cardiovascular health outcomes. Comparative changes with RYGB and VSG in prevalent cardiovascular disease (CVD) risk factors such as hypertension and dyslipidemia, as well as overall CVD risk, have not been studied. There is also almost nothing known about the comparative safety of VSG and RYGB beyond the standard reporting period of 30 days after surgery. GAP 2: Almost nothing has been published regarding the heterogeneity in comparative effectiveness and safety between these two procedures. Even among the few small published comparative studies, there is no understanding of how heterogeneity in effects might determine which procedure is most appropriate for certain kinds of patients. Our own preliminary work clearly shows that racial/ethnic minority patients have different weight loss responses to RYGB (losing less weight) but similar responses to VSG (no difference in weight loss), compared to whites. Given these major gaps in knowledge, large-scale comparative effectiveness studies, using real-world clinical populations are urgently needed to improve bariatric treatment decision-making for severely obese patients, especially with respect to CVD outcomes. We have designed such a study to compare the effectiveness of VSG and RYGB for hypertension, dyslipidemia, and diabetes remission as well as overall CVD risk reduction in more than 17,000 VSG and 11,000 RYGB patients, from a real-world health care setting with an integrated electronic medical record. This combined sample size is over 20 times the number of VSG and RYGB patients that have been directly compared in case series and controlled trials to date (n = 1,041). No other studies in the literature have the diversity of bariatric surgery patients in our sample, who are 56% Hispanic or non-Hispanic Black. We will apply innovative econometric techniques to deal with selection biases in observation data and study heterogeneity in effects to inform clinical knowledge and identify areas where further studies are needed. We have assembled an experienced, interdisciplinary research and clinical care team to address the following specific aims over a median three years of follow-up.
Personnel
Basu, Anirban, Principal Investigator, Professor, Department of Pharmacy • Khandelwal, Saurabh, Key Personnel, Asst Professor Without Tenure, Surgery • Weatherford, Sally, Administrative Contact, Administrator, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, Department of Pharmacy • Weatherford, Sally, eGC1 Preparer, Administrator, Department of Pharmacy
Optimizing Busulfan: Efficacy, Toxicity, and Pharmacometabolomics.
LIN, YVONNE S. , Pharmaceutics
Award Date: 11/29/2017
Sponsor: City of Hope National Medical Center Amount: $120836
Abstract
Dr. Lin will oversee the activities of the UW Pharmacokinetics Laboratory (PK Lab). The UW PK Lab staff will collect samples from clinical trial participants, quantitate those samples for select busulfan metabolites (i.e., tetrahydrothiophenium ion (THT+), THT+ 1-oxide, sulfolane, and 3-hydroxysulfolane) and communicate those results to the Dr. McCune at City of Hope and Dr. Baker at Fred Hutch.
Personnel
Lin, Yvonne S., Principal Investigator, Associate Professor, Pharmaceutics • Phillips, Brian, Other, Research Scientist/engineer 3, Pharmaceutics • Shireman, Laura M., Other, Research Coordinator, Pharmaceutics • Men, Alex J, Other, Student Assistant, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants and Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, Budget Contact, Grants and Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/specialist, Pharmaceutics
UW Patient Centered Outcomes Research Institutional Mentored Career Development Program (K12).
SULLIVAN, SEAN , Department Of Pharmacy
Award Date: 11/20/2017
Sponsor: Agency for Healthcare Research and Quality (AHRQ) Amount: $344099
Abstract
This program aims to develop early career scientists in PCOR evidence development, adoption and evaluation. At the completion of their training, Scholars will have cutting edge PCOR skills and a grounding in implementation and dissemination science. Our overall aims are to (1) provide Scholars with multidisciplinary training, (2) activate Scholars to utilize existing and unparalleled opportunities within the UW and affiliated institutions to learn PCOR and CER from experts with ongoing projects, multidisciplinary teams, data resources, and real world populations and stakeholders, (3) create an environment that supports the early research efforts of junior faculty, infuses them with the excitement of comparative effectiveness research and nurtures their early career development and productivity and aids in ensuring a long term career in conducting and teaching PCOR.
Personnel
Sullivan, Sean, Principal Investigator, Professor, Department of Pharmacy • Devine, Emily E., Mentor, Associate Professor, Department of Pharmacy • Patrick, Donald L., Mentor, Professor, Health Services/Main • Weatherford, Sally, Administrative Contact, Administrator, Department of Pharmacy • Kraegel, Paul K., Budget Contact, Program Operations Specialist, Department of Pharmacy • Kraegel, Paul K., eGC1 Preparer, Program Operations Specialist, Department of Pharmacy
PHPDA/SHAG Prevention of Medical Mishaps.
DOWNING, DONALD F , Department Of Pharmacy
Award Date: 11/17/2017
Sponsor: Senior Housing Assistance Group (SHAG) Amount: $11300
Abstract
The Senior Housing Assistance Group (SHAG) has received a grant through the Pacific Hospital Preservation and Development Authority (PHPDA) with the support of the PI and the UW Department of Pharmacy. The PI and project team will help the sponsor examine the unmet healthcare and social needs of SHAG residents and to develop an informed long-term strategy to keep these residents in their homes, living independently as long as possible.
Personnel
Downing, Donald F, Principal Investigator, Endowed Faculty Fellowship in Innovative Pharmacy, Department of Pharmacy • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, Pharm - A, Department of Pharmacy • Luetjen, Karen H., eGC1 Preparer, Grants And Contracts Manager/specialist, Pharm - A, Department of Pharmacy
Oral contraceptive drug interactions.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 11/13/2017
Sponsor: GlaxoSmithKline, Inc. Amount: $49992
Abstract
The objective of this project is to develop a Physiologically based pharmacokinetic (PBPK) model (either using simcyp or matlab) for the most common estrogen and progestin oral contraceptives to allow prediction of clinical drug-drug interactions (DDIs) with select oral contraceptives (OC's). The model development will establish the scope of experimental wet lab work that will need to be done to truly validate a model so it can be used for clinical DDI prediction.
Personnel
Isoherranen, Nina, Principal Investigator, Professor, Pharmaceutics • Shum, Hiu M, Other, Predoctoral Research Associate 2, PCEUT - ISOHERRA, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics • Royall, Frederick, Budget Contact, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics
Inter-species differences in kidney drug transporter abundance.
PRASAD, BHAGWAT , Pharmaceutics
Award Date: 11/01/2017
Sponsor: Pfizer, Inc. Amount: $55000
Abstract
A validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomics assay will be used to simultaneously quantify changes in ~20 kidney cortex transporters across multiple toxicological species and humans. This approach uses a triple quadrupole MS instrument to achieve selectivity by quantifying specific daughter ions generated from surrogate peptides of the transporter protein (Prasad DMD, 2016; Vrana CPT:PSP, 2017). This allows multiplexed quantification of proteins in a complex sample without prior isolation and is not limited by the availability or quality of antibodies.
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, Pharmaceutics • Karasu, Matthew Thomas, Other, Project Appointment - Overtime Exempt, PCEUT - PRA, Pharmaceutics • Bhatt, Deepak Kumar, Co-Investigator, Senior Fellow, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics • Royall, Frederick, Budget Contact, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics
Impact of Malaria Co-Infection on HIV Vaccination .
KLATT, NICHOLE, Pharmaceutics
Award Date: 10/26/2017
Sponsor: National Institutes of Health (NIH) Amount: $349968
Abstract
HIV and malaria are two of the most devastating infectious diseases in the world. In 2015, these diseases together caused over 1.4 million deaths. Although advances have been made in preventing new infections of both HIV and malaria, the risk of infection with either disease in the world’s poorest nations is still great. Furthermore, as HIV and malaria are endemic to similar geographical areas, this overlap constitutes great risk for co-infection of individuals, which could fuel the spread of both diseases. Moreover, HIV and malaria infection have been shown to cause similar gastrointestinal pathologies, including disruption of the epithelial barrier and altered intestinal immune function. As infection across the rectal mucosa constitutes a major route for sexual transmission of HIV, it is possible that prior infection with malaria could increase the risk of acquisition of HIV, should exposure of this mucosal membrane occur. Importantly, as the biomedical research field moves closer to the development of an effective vaccine to prevent new HIV infections, it will be critical to take into account alterations in mucosal phenotype and function that may occur due to malaria infection, as these changes could impact the efficacy of the HIV vaccine. Here, we aim to determine how concurrent malaria infection could alter the efficacy of SHIV vaccination in rhesus macaques. We will assess immunological and microbial alterations in the intestinal mucosa during malaria infection and track these changes throughout subsequent SHIV vaccination and SHIV challenge, in order to elucidate how malaria may alter HIV vaccine responses and thus diminish protection from SHIV infection. These studies will generate critical knowledge of the impact of malaria on HIV vaccination strategies, which will aid in the development of vaccines that take into account environmental factors such as other co-endemic infectious diseases, and thus be effectively employed in the developing world, where the need for an HIV vaccine is the greatest.
Personnel
Klatt, Nichole, Principal Investigator, Asst Professor Without Tenure, Pharmaceutics • Manuzak, Jennifer, Key Personnel, Senior Fellow, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants And Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, Budget Contact, Grants and Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/specialist, Pharmaceutics
Natural Product-Drug Interaction Research: The Roadmap to Best Practices.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 10/23/2017
Sponsor: Washington State University (WSU) Amount: $384360
Abstract
Administrative CoreThe Administrative Core under the parent grant has a two-fold responsibility. At the program level, the Administrative Core coordinates the basic administrative and financial services to the Cores and participating institutions. At the project level, the Administrative Core is charged with 1) supporting the oversight Steering Committee in monitoring and approving selection of the priority NPs and completion of the Statements of Work (SOWs) by the Pharmacology Core; 2) participating in the Interaction Project teams to monitor progress and the transfer of samples and data to the Analytical and Pharmacology Cores, respectively; 3) developing and disseminating the Recommended Approaches (RAs); and 4) coordinating with the Informatics Core to develop and maintain the web portal to allow public access to Best Practices and archived data from the Interaction Projects.The Administrative Core component of this subcontract supports the effort of Dr. Danny Shen (Co-I). Dr. Shen, who formerly was the PI of the U54 grant before he assumed semi-retirement in September of 2016, will mainly provide advice and counsel for the first three elements of the programmatic function of the Administrative Core, namely design and construction of the SOWs, execution of the Interaction Projects, and development of the RAs.Pharmacology CoreFor the remaining 3-year period of the parent grant, the Pharmacology Core has the principal responsibility of designing and guiding the implementing the Interaction Projects through the development of SOWs. The development path begins with a carefully orchestrated set of preclinical studies on selected natural product-drug interactions (NPDIs) and ends with a definitive assessment of the risk or safety of the NPDIs, or the need for further investigation. Using rigorous, predefined decision trees as guides, detailed SOWs for the selected NPDIs will be developed. These SOWs represent key deliverables of this Core and will be used subsequently to develop RAs for NPDI research.The Pharmacology Core component of this subcontract supports the efforts of Dr. Allan Rettie (Co-I) and Dr. Jashvant Unadkat (Co-I), two preeminent translational and clinical pharmacologist. The two Co-I will work with the PI of the parent grant, Dr. Mary Paine in developing the SOWs for the three selected priority natural products: green tea, goldenseal and cannabis. UW portion of the Pharmacology Core will conduct all the necessary preclinical studies for identifying potential drug interactions with cannabis extracts and its constituent cannabinoids. At present, the preclinical studies will largely consist of validated in vitro screening assays for known drug metabolizing enzymes and drug transporters. Bench support will be provided by a qualified postdoctoral fellow, Dr. Neha Maharao.Analytical CoreUnder the parent grant, the Analytical Core is charged with 1) characterizing the bioactive constituents of the priority natural products selected for the Interaction Projects, 2) synthesizing and supplying the purified bioactive constituents for preclinical studies on drug interaction potentials, and 3) supporting the analysis of samples generated from both the preclinical and human subject studies under the Interaction Projects.The Analytical Core component of this subcontract will focus on the third charge, mainly to provide the critical analytical support for the preclinical studies on standardized cannabis extracts obtained from National Institute on Drug Abuse (NIDA) in regards to their potential for modulating drug metabolizing enzymes and drug transporters. The analysis tasks will consist of development of sensitive and specific mass-spectrometry based assays for the cannabinoid constituents present in the cannabis extracts (i.e., the perpetrators) and the drug and/or metabolites of the probes used in the enzyme or transporter screens. All assays will be performed in our shared research resource PK Lab in the Department of Pharmaceutics.A secondary assignment for the UW component of the Analytical Core is to provide back-up support or overflow capacity in the analysis of biological samples (i.e., blood/plasma and urine) collected from human subject studies under the Interaction Projects. At present, the analyses are being handled by Dr. Mary Paine’s laboratory at WSU. UW PK Lab will provide back-up LC-MS/MS support on those occasions when the WSU LC-MS facility develops major instrumentation problems. The PK Lab will also handle overflow samples from WSU according well-defined Standard Operating Procedures (SOPs).
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, Pharmaceutics • Maharao, Neha, Other, Senior Fellow, Pharmaceutics • Phillips, Brian, Other, Research Scientist/engineer 3, Pharmaceutics • Shen, Danny D, Co-Investigator, Professor Emeritus, Pharmaceutics • Unadkat, Jashvant D, Co-Investigator, Professor, Pharmaceutics • Rettie, Allan E., Co-Investigator, Professor, Medicinal Chemistry • Royall, Frederick, Administrative Contact, Grants and Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, Budget Contact, Grants and Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/specialist, Pharmaceutics
Screening of Investigational Compounds to Treat, Modify or Prevent Epilepsy for the NINDS Epilepsy Therapy Screening Program (ETSP).
WHITE, HAROLD STEVE , Department Of Pharmacy
Award Date: 10/20/2017
Sponsor: University of Utah Amount: $255660
Abstract
The systemic kainic acid (KA)-induced status epilepticus (SE) model in rats is an etiologically-relevant animal model of epileptogenesis. All of the clinical characteristics observed in human patients with temporal lobe epilepsy (TLE) are also observed in the rat systemic KA model of SE and TLE. Moreover, the systemic low-dose KA paradigm is ideally suited for preclinical drug screening studies to evaluate the long-term process of epileptogenesis. As a first attempt to identify novel and potentially efficacious antiepileptogenic agents, it is necessary to define whether administration of the investigational compound during the SE insult or immediately after (e.g. during the latent period) can first modify presentation and severity of spontaneous recurrent seizures, as well as attendant comorbidities, in the rat KA-SE model of epileptogenesis. The goal of the proposed studies is to determine whether administration of promising investigational anticonvulsant compounds can also modify or attenuate the presentation of spontaneous recurrent seizures days to weeks after SE, as well as modify the SE-induced behavioral deficits associated with TLE.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, Department of Pharmacy • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants and Contracts Manager/Specialist, Pharm - A, Department of Pharmacy • Luetjen, Karen H., eGC1 Preparer, Grants and Contracts Manager/Specialist, Pharm - A, Department of Pharmacy
Optimizing Busulfan: Efficacy, Toxicity, and Pharmacometabolomics.
LIN, YVONNE S. , Pharmaceutics
Award Date: 10/20/2017
Sponsor: City of Hope National Medical Center Amount: $64280
Abstract
Dr. Lin will oversee the activities of the UW Pharmacokinetics Laboratory (PK Lab). The UW PK Lab staff will collect samples from clinical trial participants, quantitate those samples for select busulfan metabolites (i.e., tetrahydrothiophenium ion (THT+), THT+ 1-oxide, sulfolane, and 3-hydroxysulfolane) and communicate those results to the Dr. McCune at City of Hope and Dr. Baker at Fred Hutch.
Personnel
Lin, Yvonne S., Principal Investigator, Associate Professor, Pharmaceutics • Phillips, Brian, Other, Research Scientist/engineer 3, Pharmaceutics • Shireman, Laura M., Other, Research Coordinator, Pharmaceutics • Men, Alex J, Other, Student Assistant, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants and Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, Budget Contact, Grants and Contracts Manager/specialist, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/specialist, Pharmaceutics
WWARN Malaria Elimination Safety Study Group.
STERGACHIS, ANDREAS S , Department Of Pharmacy
Award Date: 10/18/2017
Sponsor: Liverpool School of Tropical Medicine Amount: $7077
Abstract
The University of Washington will work with the Liverpool School of Tropical Medicine, Oxford University’s WorldWide Antimalarial Resistance Network (WWARN), and the University of California-San Francisco’s Malaria Elimination Initiative to establish a global study group focused on assessment of the safety of single low-dose primaquine. Eventually, a pooled analysis of the safety of single low-dose primaquine to interrupt P. falciparum will be conducted under the auspices of WWARN.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, Department of Pharmacy • Weatherford, Sally, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants and Contracts Manager/Specialist, Pharm - A, Department of Pharmacy • Luetjen, Karen H., eGC1 Preparer, Grants and Contracts Manager/Specialist, Pharm - A, Department of Pharmacy
Time and Dose-Response in PTZ Challenge Model.
WHITE, HAROLD STEVE , Department Of Pharmacy
Award Date: 10/05/2017
Sponsor: Takeda California, Inc. (TCAL) Amount: $4750
Abstract
Personnel
White, Harold Steve, Principal Investigator, Chair, Department of Pharmacy • Weatherford, Sally, Administrative Contact, Administrator, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, Department of Pharmacy • Ehlers, Sellyna A, eGC1 Preparer, Grants And Contracts Manager/specialist, Department of Pharmacy • Ehlers, Sellyna A, Budget Preparer, Grants And Contracts Manager/specialist, Department of Pharmacy
CDA for OVID Therapeutics.
HALISKI, MELISSA , Department Of Pharmacy
Award Date: 10/04/2017
Sponsor: Ovid Therapeutics Amount: $57650
Abstract
Personnel
Haliski, Melissa, Principal Investigator, Research Assistant Professor, Department of Pharmacy • White, Harold Steve, Key Personnel, Professor, Department of Pharmacy • Weatherford, Sally, Administrative Contact, Administrator, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, Department of Pharmacy • Weatherford, Sally, eGC1 Preparer, Administrator, Department of Pharmacy
Assessment of quality of liver subcellular fractions as in vitro models of drug metabolism.
PRASAD, BHAGWAT , Pharmaceutics
Award Date: 10/03/2017
Sponsor: Genentech, Inc. Amount: $50000
Abstract
In vitro drug metabolism data obtained in the enriched subcellular fractions such as microsomes and cytosol derived by differential centrifugation are commonly utilized for the in vitro to in vivo extrapolation (IVIVE) of drug clearance. The purity of subcellular fractions and the accurate estimation of physiologically relevant scaling factor, i.e., microsomal or cytosolic protein per gram of tissue, are the key parameters in the implementation of IVIVE. Further, while the localizations of traditional hepatic DMEs (CYPs, UGTs) are well characterized, localization of other DMEs including carboxylesterases (CESs), AOX, paraoxonases (PONs), etc., is not well known. This knowledge gap is a major limitation in in the IVIVE of non-CYP mediated drug clearance.
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, Pharmaceutics • Vrana, Marc A, Other, PREDOCTORAL RESEARCH ASSOCIATE 2, PCEUT - PRASAD L, Pharmaceutics • Royall, Frederick, Administrative Contact, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics • Royall, Frederick, Budget Contact, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics • Royall, Frederick, eGC1 Preparer, Grants and Contracts Manager/Specialist, PCEUT - A, Pharmaceutics
Maternal Immunization Pharmacovigilance in Low and Middle-Income Countries.
STERGACHIS, ANDREAS S , Department Of Pharmacy
Award Date: 10/02/2017
Sponsor: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Amount: $12331
Abstract
Vaccination programs represent a cornerstone of public health, and have resulted in cost-effective global health strategies that have prevented disease, death, and disability worldwide, including among pregnant women and newborns. Extensive work has gone into the field of pharmacovigilance for low- and middle-income country (LMIC) settings, but not for vaccination programs in pregnant women. This project, commissioned by the Bill & Melinda Gates Foundation to the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS), an Initiative of Seattle Children's, will consist of conducting a review of existing scientific literature, guidelines, and programs relevant to vaccine safety and, through adaptation of this existing body of work and in partnership with key experts and stakeholders worldwide, build a strategic framework for maternal immunization pharmacovigilance systems in LMIC. The UW principal investigator is requested by GAPPS to serve as a technical expert and one of the lead authors of the report, contributing specifically to topic areas related to pharmacovigilance systems in LMICs.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, Department of Pharmacy • Brase, Jessica E., Administrative Contact, Administrator, Department of Pharmacy • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, Pharm - A, Department of Pharmacy • Ehlers, Sellyna A, eGC1 Preparer, Grants And Contracts Manager/specialist, Department of Pharmacy