Grants and Awards

One-year period ending April 1, 2018 . Click on a title to read more.
Awards information as defined in UW SAGE.
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