Grants and Awards

One-year period ending September 30, 2019. Click on a title to read more.
Awards information as defined in UW SAGE.
Population-based Interventions to Improve Behavioral Health in a Tribal Healthcare System.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 09/26/2019
Sponsor: Southcentral Foundation Amount: $88808
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 • Thornton, Timothy A., Key Personnel, Associate Professor, N/A • Trinidad, Susan B, Key Personnel, Research Scientist/engineer 4, BIOETHICS & HUMANITIES • Calamia, Justina C., 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
Exploring the uptake of value-based formularies and their application to specialty drugs.
HANSEN, RYAN , Department Of Pharmacy
Award Date: 09/23/2019
Sponsor: PhRMA Foundation Amount: $50000
Abstract
The goal of this study is to explore the uptake of value-based formularies and their application to specialty drugs.
Personnel
Hansen, Ryan, Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Dept Of Pharmacy, Budget Contact • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Brouwer, Elizabeth D, Application PI, Teaching Assistant (E S UAW ASE), DEPARTMENT OF PHARMACY
Early Postdoc Mobility Fellowship.
Unadkat, Jashvant D , Pharmaceutics
Award Date: 09/18/2019
Sponsor: Swiss National Science Foundation Amount: $77147.21
Abstract
Early Postdoc.Mobility fellowships are designed for early-career postdocs who wish to enhance their scientific profile by working at a research institution abroad. The fellowships include a grant towards living costs, a flat-rate for travel expenses and a contribution to research, conference and matriculation costs if necessary. In principle, these fellowships are awarded for 18 months, or for no less than 12 months in justified cases.
Personnel
Unadkat, Jashvant D, Principal Investigator, Professor, PHARMACEUTICS • Storelli, Flavia, Fellow, 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 anticholinergic and dopamine receptor blocking drug exposure on Parkinson Disease trajectory and outcomes.
GRAY, SHELLY L. , Department Of Pharmacy
Award Date: 09/17/2019
Sponsor: University of Pennsylvania Amount: $31728
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 • Luetjen, Karen H., Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Dept Of Pharmacy, Budget Contact • Dept Of Pharmacy, eGC1 Preparer
Pharmacology of Drugs of Abuse During Pregnancy.
Unadkat, Jashvant D , Pharmaceutics
Award Date: 09/16/2019
Sponsor: National Institute on Drug Abuse (NIDA) Amount: $1202432
Abstract
Use of marijuana amongst pregnant women in the US is increasing. A major concern of marijuana use by pregnant women is the transfer of cannabinoids across the placental barrier, leading to placental (and therefore fetal) toxicity. Studies proposed in this P01 will elucidate how and to what extent the maternal-placental-fetal exposure to cannabinoids is altered during pregnancy and how to predict these changes. Completion of these studies will significantly advance our ability to predict the risks of using marijuana during pregnancy and have the potential to reveal strategies to minimize such risks. This P01 addresses a significant public health problem that cannot be addressed using the traditional approach of conducting a clinical trial.
Personnel
Unadkat, Jashvant D, Principal Investigator, Professor, PHARMACEUTICS • Sachar, Madhav, Fellow, Senior Fellow, PHARMACEUTICS • Czuba, Lindsay, Fellow, Senior Fellow, PHARMACEUTICS • Yabut, King, Other, Research Assistant (E S UAW ASE), PHARMACEUTICS • Chamonica Hernandez, Marle, Other, Research Study Assistant (NE S SEIU 925 Non Supv), OBGYN/ADMIN • Billington, Sarah, Other, Senior Fellow, PHARMACEUTICS • Patilea-Vrana, Gabriela, Other, PREDOCTORAL RESEARCH ASSOCIATE 2, PCEUT - UNADKAT, PHARMACEUTICS • Taylor, Susan Margaret, Other, COUNSELING SERVICES COORDINATOR, OPPE Staff, PHARMACY-DEAN'S OFFICE • Nielsen, Iris, Other, LIMITED TERM APPOINTMENT - PROF STAFF, Department, DEPARTMENT OF MEDICINE • Macdonald, James, Other, RESEARCH SCIENTIST/ENGINEER 3, Enviro & Occup Heal, ENVIRO & OCCUP HEALTH • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Han, Lyrialle W, Other, Research Assistant (E S UAW ASE), PHARMACEUTICS • Amory, John K., Co-Investigator, Professor, DEPARTMENT OF MEDICINE • Prasad, Bhagwat, Co-Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Kelly, Edward J, Co-Investigator, Associate Professor without Tenure, PHARMACEUTICS • Isoherranen, Nina, Co-Investigator, Professor, PHARMACEUTICS • Mao, Qingcheng, Co-Investigator, Associate Professor, PHARMACEUTICS • Benson, Lyndsey S, Co-Investigator, Acting Assistant Professor, OBGYN/ADMIN • Bammler, Theodor K., Co-Investigator, RESEARCH SCIENTIST/ENGINEER-SENIOR, Enviro & Occup, ENVIRO & OCCUP HEALTH • Royall, Frederick, Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS • Royall, Frederick, Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Administrative Supplement - Natural Product-Drug Interaction Research: The Roadmap to Best Practices.
Thummel, Kenneth E. , Pharmaceutics
Award Date: 09/11/2019
Sponsor: Washington State University (WSU) Amount: $238767
Abstract
The University of Washington subcontract under Dr. Jashvant Unadkat will be responsible for studies evaluating the role of cannabinoids as perpetrators of drug interactions, including: conducting the in vitro inhibition studies using cannabis brownies and the major metabolites of tetrahydrocannabinol (THC), 11-hydroxy tetrahydrocannabinol (11-OH-THC) and 11-nor-carboxy tetrahydrocannabinol (COOH-THC), bioanalysis of plasma and urine samples of the cannabis clinical study (that will be conducted at Johns Hopkins Univ), as well as pharmacokinetic analysis of the clinical study data; and developing and validating LC-MS/MS methods to quantify the cannabinoids as well as all CYP probes and their respective metabolites for the in vitro and clinical study samples.
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, PHARMACEUTICS • Maharao, Neha, Other, Senior Fellow, PHARMACEUTICS • Unadkat, Jashvant D, Co-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
Natural Product-Drug Interaction Research: The Roadmap to Best Practices.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 09/11/2019
Sponsor: Washington State University (WSU) Amount: $220351
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
Model for Economic Analysis of Sickle cell cURE (MEASURE).
Basu, Anirban , Department Of Pharmacy
Award Date: 09/09/2019
Sponsor: National Heart, Lung, and Blood Institute (NHLBI) Amount: $1736955
Abstract
The current proposal aims to develop a simulation model that can be used to demonstrate the potential national impact of specific curative therapies for sickle cell disease (SCD) and the distribution of that impact on payers, employers, and families over the lifetime of the patients.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • MORGAN, ANTHONY R, Other, Research Coordinator (E S 7), DEPARTMENT OF PHARMACY • Devine, Emily E., Co-Investigator, Professor, DEPARTMENT OF PHARMACY • Bender, Michael A., Co-Investigator, Associate Professor without Tenure, PEDIATRICS • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), 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
Personalized Risk-AdaptIve Surveillance strategies in cancEr (PRAISE).
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 09/06/2019
Sponsor: National Institutes of Health (NIH) Amount: $449121
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, 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, N/A • Shankaran, Veena, Co-Investigator, Assoc Professor Without Tenure, DEPARTMENT OF MEDICINE • Inoue, Lurdes, Co-Investigator, Professor, N/A • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Ahmed, Saveena, eGC1 Preparer, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY
USAID MTAPS: Asia Bureau.
STERGACHIS, ANDREA S. , Department Of Pharmacy
Award Date: 09/06/2019
Sponsor: Management Sciences for Health (MSH) Amount: $18736
Abstract
University of Washington (UW) has been selected by MSH to support pharmacovigilance activities in theMTaPS program. MTaPS scoping visits have been conducted and work plans developed for the differentcore and field buy-in portfolios. As part of this, MTaPS has identify pharmacovigilance (PV) activitiesUniversity of Washington will support (i.e. provide technical assistance for country capacity building inpharmacovigilance and patient safety as part of the work plan for several countries’ work plan includingMozambique, Rwanda, Bangladesh and Philippines), and will issue specific task orders for conducting thiswork. Additionally, MTaPS would like to get support from University of Washington in the planning,brainstorming and cross-cutting pharmacovigilance activities for the Asia cross bureau portfolio anddevelopment of PV agenda for Africa that benefits a number of countries in the two regions during thelength of the project.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Meds4All VentureWell Stage 2.
STERGACHIS, ANDREAS S , Department Of Pharmacy
Award Date: 09/05/2019
Sponsor: VentureWell Amount: $20000
Abstract
MedsForAll is developing a novel ampule medication cartridge-based drug delivery system that leverages an existing medical infrastructure. The ampule medication cartridge is available globally, standardized to universal ISO standards and is already used every day in hospitals, clinics, pharmacies and by patients but requires technical ability for usage. Our autoinjector technology eliminates these technical requirements allowing any patient access to lower cost autoinjector with equal equivalency.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • LEE, RICHARD WON, Key Personnel, Fellow, DEPARTMENT OF PHARMACY • Swanson, Shawn A, Key Personnel, Fellow, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Treatment for Acute Pain.
Devine, Emily E. , Department Of Pharmacy
Award Date: 09/03/2019
Sponsor: Oregon Health and Science University (OHSU) Amount: $99778
Abstract
University of Washington (UW) personnel will work with the investigators and staff of the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University to conduct one systematic review for “Treatments for Acute Pain” UW personnel will use scientifically rigorous methods adopted by the Agency for Healthcare Research and Quality (AHRQ) EPC Program, as referenced in the RFTO. The University of Washington investigators and staff will undertake the following tasks during the conduct of a Large Systematic Review for this topic:Large Systematic Review Update•Review literature search results and contribute to design and completion of data collection forms •Contribute to risk of bias assessment, evidence synthesis and analyses•Suggest expert peer reviewers•Draft sections of the evidence review for AHRQ review, peer review, and public comment•Contribute to review of update literature search•Review and respond to peer reviewer, public, and AHRQ comments on the draft report•Prepare sections of the final report of the systematic evidence review•Conduct comprehensive review of deliverables, with a focus on clinical accuracy and meaningfulness
Personnel
Devine, Emily E., Principal Investigator, Professor Without Tenure, DEPARTMENT OF PHARMACY • Gordon, Debra, Key Personnel, TEACHING ASSOCIATE, Anesthesiology and Pain Medici, ANESTHESIOLGY&PAIN MED • Kraegel, Paul K., Other, PROGRAM OPERATIONS SPECIALIST, Pharm - Admin, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, 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
USAID MTAPS: Tanzania.
Stergachis, Andreas S , Department Of Pharmacy
Award Date: 08/30/2019
Sponsor: Management Sciences for Health (MSH) Amount: $59990
Abstract
University of Washington (UW) has been selected by MSH to support pharmacovigilance activities in theMTaPS program. MTaPS scoping visits have been conducted and work plans developed for the differentcore and field buy-in portfolios. As part of this, MTaPS has identify pharmacovigilance (PV) activitiesUniversity of Washington will support (i.e. provide technical assistance for country capacity building inpharmacovigilance and patient safety as part of the work plan for several countries’ work plan includingMozambique, Rwanda, Bangladesh and Philippines), and will issue specific task orders for conducting thiswork. Additionally, MTaPS would like to get support from University of Washington in the planning,brainstorming and cross-cutting pharmacovigilance activities for the Asia cross bureau portfolio anddevelopment of PV agenda for Africa that benefits a number of countries in the two regions during thelength of the project.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Werth, Brian, Key Personnel, Associate Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Empowering the Annual Health Econometrics Workshop.
BASU, ANIRBAN , Department Of Pharmacy
Award Date: 08/19/2019
Sponsor: Agency for Healthcare Research and Quality (AHRQ) Amount: $27417
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 • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Landscape analysis: Readiness for Maternal Immunization Sentinel Site Active Safety Surveillance in LMICs.
Stergachis, Andreas S , Department Of Pharmacy
Award Date: 08/14/2019
Sponsor: Tulane University Amount: $173844
Abstract
We will define the landscape for integrated active safety surveillance after maternal immunization by reviewing the literature, building consensus among experts, and identifying potential sentinel sites in Africa. “Integrated” systems are defined as those that have the potential to link active safety surveillance to routine Maternal and Child Health (MCH) data collection.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • ZARAA, SABRA, Other, Research Assistant (E S UAW ASE), DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Comparative efficacy of perampanel, levetiractetam and lacosamide in the post-status epilepticus model of epilepsy and the impact of variable medication adherence on seizure control.
White, Harold Steve , Department Of Pharmacy
Award Date: 08/12/2019
Sponsor: Eisai Inc. Amount: $776850
Abstract
The overall study objective is to evaluate the acute anticonvulsant activity of investigational compounds in rodent models of seizure.
Personnel
White, Harold Steve, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Isoherranen, Nina, Key Personnel, Professor, PHARMACEUTICS • Haliski, Melissa, Co-Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, 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 • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Program on Genetic and Dietary Predictors of Drug Response in Rural and AI/AN.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 08/07/2019
Sponsor: National Institute of General Medical Sciences (NIGMS) Amount: $1519987
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 • 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 • Shaikh, Abdul Basit A H, Other, Senior Fellow, PHARMACEUTICS • Rettie, Allan E., Co-Investigator, Professor, MEDICINAL CHEMISTRY • Thornton, Timothy, Co-Investigator, Associate Professor, N/A • 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 • Sabath, Daniel E., Co-Investigator, Assoc Professor Without Tenure, LAB MEDICINE • Prasad, Bhagwat, Co-Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Burke, Wylie, Multiple PI, Professor, BIOETHICS & HUMANITIES • 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
Community Pharmacist Epilepsy Services Program.
Bacci, Jennifer Lynn , Department Of Pharmacy
Award Date: 08/07/2019
Sponsor: UCB Pharma, Inc. Amount: $417157
Abstract
This project seeks to develop and evaluate a community pharmacy-based population health intervention for people living with epilepsy.
Personnel
Bacci, Jennifer Lynn, Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • White, Harold Steve, Key Personnel, Professor, DEPARTMENT OF PHARMACY • Stergachis, Andreas S, Key Personnel, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Ahmed, Saveena, eGC1 Preparer, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY
USAID MTAPS: Task Order #2 & Task Order #3.
Stergachis, Andreas S , Department Of Pharmacy
Award Date: 08/06/2019
Sponsor: Management Sciences for Health (MSH) Amount: $90343.03
Abstract
University of Washington (UW) has been selected by MSH to support pharmacovigilance activities in theMTaPS program. MTaPS scoping visits have been conducted and work plans developed for the differentcore and field buy-in portfolios. As part of this, MTaPS has identify pharmacovigilance (PV) activitiesUniversity of Washington will support (i.e. provide technical assistance for country capacity building inpharmacovigilance and patient safety as part of the work plan for several countries’ work plan includingMozambique, Rwanda, Bangladesh and Philippines), and will issue specific task orders for conducting thiswork. Additionally, MTaPS would like to get support from University of Washington in the planning,brainstorming and cross-cutting pharmacovigilance activities for the Asia cross bureau portfolio anddevelopment of PV agenda for Africa that benefits a number of countries in the two regions during thelength of the project.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Babigumira, Joseph Brian, Key Personnel, Associate Professor WOT, GLOBAL HEALTH • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Hybrid structural mass spectrometry for rapid site-specific glycan structural elucidation.
GUTTMAN, MIKLOS , Medicinal Chemistry
Award Date: 08/05/2019
Sponsor: National Institutes of Health (NIH) Amount: $426577
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
Targeted Long-acting Combination Antiretroviral Therapy (TLC-ART) 5UM1 AI120176.
HO, RODNEY J.Y. , Pharmaceutics
Award Date: 07/30/2019
Sponsor: National Institutes of Health (NIH) Amount: $1708470
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 two 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 • Jonsson, Christine Anne, Key Personnel, Research Consultant, DEPARTMENT OF MEDICINE • Tapia, Kenneth A, Other, Research Consultant, GLOBAL HEALTH • McConnachie, Lisa, Other, Research Scientist/engineer 4, PHARMACEUTICS • Kinman, Loren M., Other, Research Scientist/engineer 3, PHARMACEUTICS • Gulati, Gaurav Kumar, Other, Research Scientist Engineer 3, PHARMACEUTICS • Mu, Qingxin, Other, RESEARCH SCIENTIST/ENGINEER 3, PHARM:Pharmaceutics, 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 • Hladik, Florian, Co-Investigator, Research Associate Professor, OBGYN/ADMIN • Hu, Shiu-Lok, Co-Investigator, Professor, PHARMACEUTICS • Shen, Danny D, Co-Investigator, Professor, PHARMACEUTICS • Treuting, Piper, Co-Investigator, Assoc Professor Without Tenure, COMPARATIVE MEDICINE • 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
Antihypertensives and the Aging Brain.
Marcum, Zachary , Department Of Pharmacy
Award Date: 07/29/2019
Sponsor: National Institutes of Health (NIH) Amount: $236208
Abstract
The proposed research aims to study the association between long-term antihypertensive use and brainhealth, including Alzheimer’s disease and other dementias. Successful completion of the proposed researchcould help guide the treatment of hypertension, which affects millions of Americans, in order to maximize brainhealth.
Personnel
Marcum, Zachary, Principal Investigator, Asst Professor Without Tenure, DEPARTMENT OF PHARMACY • Crane, Paul K, Mentor, Professor without Tenure, DEPARTMENT OF MEDICINE • Keene, Christopher D, Mentor, Nancy And Buster Alvord Endowed Chair In Neuropath, PATHOLOGY • Gray, Shelly L., Mentor, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Kimura, Maya, Budget Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Preparer, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY
Effectiveness of Gastric Sleeve vs. Gastric Bypass for Cardiovascular Disease Y3.
BASU, ANIRBAN , Department Of Pharmacy
Award Date: 07/29/2019
Sponsor: Kaiser Permanente Amount: $323138
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 • Kreuter, William I., Key Personnel, RESEARCH CONSULTANT, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
The University of Washington, School of Pharmacy Research Affiliates Program on Transporters (UWRAPT).
UNADKAT, JASHVANT D , Pharmaceutics
Award Date: 07/10/2019
Sponsor: Takeda Pharmaceuticals International, Inc. Amount: $75250
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
Mechanisms of regulation of retinoic acid homeostasis.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 07/09/2019
Sponsor: National Institutes of Health (NIH) Amount: $399548
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
Structural and dynamic traits underlying phenotypic variation in HIV-1 Env.
LEE, KELLY K. , Medicinal Chemistry
Award Date: 07/08/2019
Sponsor: National Institutes of Health (NIH) Amount: $559956
Abstract
The envelope glycoprotein (Env) is the sole virally encoded antigen on the exterior of HIV-1 and hence is the target for neutralizing antibodies. In this unque role, it also dictates how the virus interacts with CD4 receptor and chemokine coreceptors, as well as host lectins on the surface of antigen presenting cells, serum proteins found in the blood, and antimicrobial peptides such as defensins in the mucosal mileu. Despite recent advances in mapping its architecture, we fundamentally lack an understanding of Env structural variation among diverse isolates. This variation is a defining trait of HIV that makes it a profound challenge for targeting by the immune system and for vaccine development. To overcome these barriers, it will be essential to understand Env structure and the structure and stability of neutralizing antibody epitopes on Env under physiological conditions, and to characterize how these vary across the diverse spectrum of Envs expressed in viral isolates. The primary goals of the proposed studies are to apply powerful structural analysis approaches to characterize Env structural diversity, to determine the consequences of structural variation on antibody binding, receptor reactivity, and interaction of Env with antigen presenting proteins such as lectins.
Personnel
Lee, Kelly K., Principal Investigator, Associate Professor, MEDICINAL CHEMISTRY • Williams, James A., Fellow, Predoctoral Research Associate 2, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Lidzbarski, Erik August Lee, Budget Contact, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
Contribution of altered lipid metabolism to resistance to cell envelope-targeting antimicrobials in MRSA.
Werth, Brian , Department Of Pharmacy
Award Date: 07/08/2019
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
Hepatic transport mechanisms of conjugated metabolites of sex steroids and AMG 853.
Prasad, Bhagwat , Pharmaceutics
Award Date: 07/08/2019
Sponsor: Amgen, Inc. Amount: $10000
Abstract
Additional scope of work for this supplement:Samples for quantitation were planned to be processed at Amgen. Preliminary data indicate lab-to-lab variability in processing the samples, which would impact data quality. The decision has been made for Dr. Prasad’s UW lab to process the samples for consistency. Processing samples was not part of the original agreement. Hence, there is a requirement for supplementing the contract to cover the cost of supplies and processing.
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Li, Yanfei, 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
Defining the Infant Immune Response to HIV.
LEE, KELLY K. , Medicinal Chemistry
Award Date: 07/08/2019
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
Lee, Kelly K., Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Budget Contact, Administrator, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, Administrator, MEDICINAL CHEMISTRY
Jiao SAA Hutch.
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 07/05/2019
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $9002
Abstract
Staff Assignment is planned to engage Boshen Jiao as pre-doc research associate on FHCRC projects.
Personnel
Devine, Emily E., Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Jiao, Boshen, Other, Graduate Fellow Stipend w/ Benefits, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Drug Action, Metabolism and Kinetics Training Grant.
ATKINS, WILLIAM M. , Medicinal Chemistry
Award Date: 07/03/2019
Sponsor: National Institute of General Medical Sciences (NIGMS) Amount: $496563
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 • 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
VIRUS-LIKE PARTICLES WITH STABILIZED TRIMERIC ENVELOPE FOR PRIME BOOST IMMUNIZATION.
HU, SHIU-LOK , Pharmaceutics
Award Date: 07/02/2019
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
Fellowship Program in Pharmacoeconomics (Beal).
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 07/02/2019
Sponsor: Allergan, Inc. Amount: $219909
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, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Fellowship Program in Pharmacoeconomics (Lee).
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 07/02/2019
Sponsor: Allergan, Inc. Amount: $219909
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, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, 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
Impact of Cannabis on Inflammation and Viral Persistence in Treated HIV/SIV.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 07/01/2019
Sponsor: University of Miami Amount: $227095
Abstract
pending
Personnel
Isoherranen, Nina, Principal Investigator, Professor, PHARMACEUTICS • Cheu, Ryan K, Other, PREDOCTORAL RESEARCH ASSOCIATE 2, PCEUT - KLATT LA, PHARMACEUTICS • Collier, Ann C, Co-Investigator, 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 • 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: 06/27/2019
Sponsor: Amgen, Inc. Amount: $115500
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
ONCOLOGY VALUE-BASED PRICING PROJECT.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 06/27/2019
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $66644.55
Abstract
The broad objective of this collaboration to design and test, with guidance from key opinion leaders, a value-based oncology drug pricing model that is adaptive to a changing healthcare system; built around the complexity of drug pricing and reimbursement; grounded in available evidence, and suitable for evaluation in a pragmatic, real-world trial. Phase I of the collaboration, described in this proposal, includes a scientifically rigorous and methodical plan for assessment of value-based pricing models, stakeholder review, and trial design, such that the trial is poised to launch immediately after Phase I is complete. Phase II plans will be addressed in a separate proposal.
Personnel
Carlson, Joshua J., Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY Bansal, Aasthaa, Multiple PI, Research 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, DEPARTMENT OF PHARMACY Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY , Dept Of Pharmacy, Budget Preparer, ,
RPPR Year 3 - Nucleoside modified mRNA based HIV vaccine.
HU, SHIU-LOK , Pharmaceutics
Award Date: 06/25/2019
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 Royall, Frederick, eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Functional Dynamics of Cytochrome P4503A4.
Atkins, William M. , Medicinal Chemistry
Award Date: 06/12/2019
Sponsor: National Institutes of Health (NIH) Amount: $468682
Abstract
Cytochrome P450s, including the isoform CYP3A4, dominate drug metabolism and are responsible for many drug-drug interactions that cause toxicity, side effects, or death. Cytochrome P450s exhibit complex kinetics and allosteric properties that make prediction of drug metabolism difficult on the basis of in vitro experiments. This proposal aims to understand the biophysical and dynamic behavior of CYPS in order to better predict drug interactions and drug clearance.
Personnel
Atkins, William M., Principal Investigator, 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
Cost Effectiveness Analysis of Stem Cell Transplant in Older MDS Patients.
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 06/12/2019
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $9850
Abstract
Dr. Bansal will serve as consortium principal investigator on Dr. Ramsey’s Ancillary cost effectiveness analysis study.
Personnel
Bansal, Aasthaa, Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY • Ahmed, Saveena, eGC1 Preparer, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY
Oxysterols in SLOS neurodevelopment: pathological role and therapy.
XU, LIBIN , Medicinal Chemistry
Award Date: 06/04/2019
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
Aligning Patient and Health Plan Incentives to Improve Value in Pharmaceutical Care: A Patient Shared Savings Model.
BASU, ANIRBAN , Department Of Pharmacy
Award Date: 06/04/2019
Sponsor: Kaiser Foundation Research Institute, a division of Kaiser Foundation Hospitals Amount: $24623.77
Abstract
The Arnold Foundation seeks to study the effects of a patient shared savings model to incentivize use of higher value medications. The topic is quite unique and highly relevant to value-based reforms in the insurance markets. Use of low value interventions poses an important problem in healthcare and there is substantial discussion about the pros and cons of financial incentives in the healthcare payer and scientific communities. This evaluation will constitute a key empirical addition to the evidence on the impact of such incentives on utilization and costs, and if successful, promote adoption and further experimentation.
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 • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Role of Alzheimer's disease-associated risk genes on seizure susceptibility.
Haliski, Melissa , Department Of Pharmacy
Award Date: 06/03/2019
Sponsor: American Epilepsy Society (AES) Amount: $50000
Abstract
Animal models of seizure and epilepsy have provided much needed preclinical information to inform on the development of over 20 antiseizure drugs available today. While these animal models have served to identify many effective therapies, there remains approximately 30% of patients with uncontrolled seizures despite available therapies. Moreover, specific patient populations are not well-represented in the preclinical antiseizure drug testing armamentarium. This specifically includes elderly patients with epilepsy. Patients with the most common disorder of aging, Alzheimer’s disease, reported to frequently have comorbid seizures. Interestingly, mounting evidence has begun to demonstrate a number of common features in both Alzheimer’s disease and epilepsy, including neuroinflammation and cognitive deficits. In an effort to better define the preclinical effects of promising investigational compounds for epilepsy in these specific patient populations, novel animal models are required that more closely replicate the clinical pathology and condition. To address this need, the present proposal seeks to characterize the age-dependent seizure susceptibility and pharmacological response to prototypical antiseizure drugs of a mouse model of familial early-onset Alzheimer's disease.
Personnel
Haliski, Melissa, Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Knox, Kevin, Other, Research Scientist/Engineer 1 (E S 6), DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • , Dept Of Pharmacy, Budget Contact, , • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Role of epithelial cell intrinsic vitamin A metabolism in regulating immune homeostasis in the gut.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 05/28/2019
Sponsor: Brown University Amount: $39262
Abstract
For the studies proposed in this application, throughout the funding period we will conduct all the labeled and unlabeled retinoic acid, retinol, retinyl ester and RBP4 measurements in the biological samples collected using our validated and sensitive liquid chromatography mass spectrometry methods, to aid in determining the role of the microbiome in regulating retinoid metabolism and vitamin A homeostasis and in understanding the role of Rdh7 in retinoid biosynthesis. 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 and aid in interpretation of the biochemistry of retinoid metabolism.
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
The plasma membrane monoamine transporter (PMAT): expression and role in mIBG disposition in neuroblastoma.
WANG, JOANNE , Pharmaceutics
Award Date: 05/14/2019
Sponsor: National Institutes of Health (NIH) Amount: $367715
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
Resistance Selection Potential of the Long Acting Lipoglycopeptides Dalbavancin and Oritavancin.
Werth, Brian , Department Of Pharmacy
Award Date: 05/13/2019
Sponsor: National Institutes of Health (NIH) Amount: $194375
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 • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, 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
Modulation of drug transport at the renal proximal tubule by uremic solutes – implications in chronic kidney disease.
YEUNG, CATHERINE , Department Of Pharmacy
Award Date: 05/10/2019
Sponsor: National Institutes of Health (NIH) Amount: $291376
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 • 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 • , Dept Of Pharmacy, eGC1 Preparer, ,
Beat MS.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 05/01/2019
Sponsor: Benaroya Research Institute at Virginia Mason Amount: $53206
Abstract
Dr. Carlson, with Dr. Bansal, will perform an economic analysis alongside of the clinical trial, BEAT-MS. Specifically, he will be responsible for the study design, data analysis, and interpretation of data for the within trial economic analyses and the development, analysis and interpretation of the simulation model for the long-term economic analysis. He will participate the development of the protocol, study materials, and data collection forms related to the CEA. He will advise on all project aims from the health economics perspective.
Personnel
Carlson, Joshua J., Principal Investigator, Associate Professor, DEPARTMENT OF PHARMACY • Bansal, Aasthaa, Key Personnel, Assistant Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, 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
Noninvasive Nonpharmacological Treatments for Chronic Pain:.
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 04/24/2019
Sponsor: Oregon Health and Science University (OHSU) Amount: $48914
Abstract
University of Washington (UW) personnel will work with the investigators and staff of the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University to conduct one systematic review for “Non-Pharmacological Treatment for Chronic Pain: An Update.” UW personnel will use scientifically rigorous methods adopted by the Agency for Healthcare Research and Quality (AHRQ) EPC Program, as referenced in the RFTO. The University of Washington investigators and staff will undertake the following tasks during the conduct of a Medium Systematic Review for these topics:Medium Systematic Review•Lead development of the telehealth decision model, including protocol design, exploration of the model, and narrative report•Contribute to literature search and review and development of data collection forms •Contribute to literature synthesis and analyses•Assist in development of list of suggested expert peer reviewers•Participate in creating the draft evidence review for AHRQ review, peer review, and public comment•Contribute to update and review of literature search•Review and assist in responding to peer reviewer, public, and AHRQ comments on the draft report•Participate in final preparation of the final report of the systematic evidence review and decision model
Personnel
Devine, Emily E., Principal Investigator, Professor Without Tenure, DEPARTMENT OF PHARMACY • Friedly, Janna L., Key Personnel, Assoc Professor Without Tenure, REHABILITATION MEDICIN • Turner, Judith A, Key Personnel, Professor Without Tenure, PSYCHIATRY ADMIN • Rundell, Sean, Key Personnel, Acting Assistant Professor-temp, REHABILITATION MEDICIN • Luetjen, Karen H., Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, 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
Opioid Treatments for Chronic Pain.
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 04/24/2019
Sponsor: Oregon Health and Science University (OHSU) Amount: $48941
Abstract
University of Washington (UW) personnel will work with the investigators and staff of the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University to conduct one systematic review for “Non-Opioid Pharmacological Treatments for Chronic Pain.” UW personnel will use scientifically rigorous methods adopted by the Agency for Healthcare Research and Quality (AHRQ) EPC Program, as referenced in the RFTO. The University of Washington investigators and staff will undertake the following tasks during the conduct of a Medium Systematic Review:Medium Systematic Review•Contribute to literature search and review •Assist in development of list of suggested expert peer reviewers•Contribute to literature synthesis and analyses•Participate in creating the draft evidence review for AHRQ review, peer review, and public comment•Contribute to update and review of literature search•Review and assist in responding to peer reviewer, public, and AHRQ comments on the draft report•Participate in final preparation and review of the final report of the systematic review
Personnel
Devine, Emily E., Principal Investigator, Professor Without Tenure, DEPARTMENT OF PHARMACY • Turner, Judith A, Key Personnel, Professor Without Tenure, PSYCHIATRY ADMIN • Kraegel, Paul K., Other, PROGRAM OPERATIONS SPECIALIST, Pharm - Admin, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, 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
Sudden cardiac arrest and circulating hydrogen sulfide.
TOTAH, RHEEM A , Medicinal Chemistry
Award Date: 04/22/2019
Sponsor: National Institutes of Health (NIH) Amount: $714436
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.H2S is an important cardiac signaling gasotransmitter responsible for the protection of cardiac cells during ischemia reperfusion injury and preventing arrhythmias. Therefor any reduction in H2S levels in cardiac tissue can be toxic. This research will identify if there is an association between SCA and H2S levels in plasma or red blood cells. The protective mechanism of H2S in the heart will also be examined and factors that regulate cardiac H2S 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 • Gharib, Sina A., Co-Investigator, Associate Professor without Tenure, DEPARTMENT OF MEDICINE • McKnight, Barbara, Co-Investigator, Professor, BIOSTATISTICS • Lemaitre, Rozenn N., Co-Investigator, Research Associate Professor, DEPARTMENT OF MEDICINE • Sotoodehnia, Nona, Multiple PI, Associate Professor without Tenure, DEPARTMENT OF MEDICINE • 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
Structure, dynamics and variation in influenza hemagglutinin-driven fusion.
LEE, KELLY K. , Medicinal Chemistry
Award Date: 04/08/2019
Sponsor: National Institutes of Health (NIH) Amount: $396951
Abstract
Lee, Kelly K., Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Hom, Nancy, Other, Senior Fellow, MEDICINAL CHEMISTRY • Williams, James A., Other, Research Assistant (E S UAW ASE), MEDICINAL CHEMISTRY • Mangala Prasad, Vidya, 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
Personnel
Lee, Kelly K., Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Hom, Nancy, Other, Senior Fellow, MEDICINAL CHEMISTRY • Williams, James A., Other, Research Assistant (E S UAW ASE), MEDICINAL CHEMISTRY • Mangala Prasad, Vidya, 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
Effects of Retinoids on CYP2D6 Activity and Variability in Special Populations.
HEBERT, MARY F , Department Of Pharmacy
Award Date: 04/05/2019
Sponsor: National Institutes of Health (NIH) Amount: $568528
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 • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, 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: 04/03/2019
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $109371
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
Affordable Emergency Medications for All.
STERGACHIS, ANDREAS S , Department Of Pharmacy
Award Date: 04/02/2019
Sponsor: VentureWell Amount: $5000
Abstract
MedsForAll is developing a novel ampule medication cartridge-based drug delivery system that leverages an existing medical infrastructure. The ampule medication cartridge is available globally, standardized to universal ISO standards and is already used every day in hospitals, clinics, pharmacies and by patients but requires technical ability for usage. Our autoinjector technology eliminates these technical requirements allowing any patient access to lower cost autoinjector with equal equivalency.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • LEE, RICHARD WON, Key Personnel, Fellow, DEPARTMENT OF PHARMACY • Swanson, Shawn A, Key Personnel, Fellow, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, 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
Effects of Informal Care for persons with Alzheimer's Disease and related dementias.
Basu, Anirban , Department Of Pharmacy
Award Date: 03/27/2019
Sponsor: University of Pennsylvania Amount: $52380
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 • Kimura, Maya, 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 • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Effects of Informal Care for persons with Alzheimer's Disease and related dementias.
Basu, Anirban , Department Of Pharmacy
Award Date: 03/27/2019
Sponsor: University of Pennsylvania Amount: $52380
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 • Kimura, Maya, 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 • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Rational Integration of clinical SEquencing (RISE).
VEENSTRA, DAVID , Department Of Pharmacy
Award Date: 03/07/2019
Sponsor: Vanderbilt University Medical Center Amount: $222283
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 • Kimura, Maya, 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
Rational Integration of clinical SEquencing (RISE).
VEENSTRA, DAVID , Department Of Pharmacy
Award Date: 03/07/2019
Sponsor: Vanderbilt University Medical Center Amount: $222283
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 • Kimura, Maya, 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
Devine VA IPA - Critical Limb Ischemia.
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 03/04/2019
Sponsor: VA Veterans Health Administration (VHA) Amount: $36000
Abstract
The purpose of this research is to improve surgical amputation level decision making in patients facing dysvascular transmetarsal (TM) amputation so that functional outcome is optimized while ensuring that patient priorities are incorporated into the decision.
Personnel
Devine, Emily E., Principal Investigator, Adjunct Associate 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, DEPARTMENT OF PHARMACY • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Use of instrumental variable approaches to assess the safety and efficacy of brand-name and generic drugs used to treat hypothyroidism.
Basu, Anirban , Department Of Pharmacy
Award Date: 03/04/2019
Sponsor: Yale University Amount: $46589
Abstract
Dr. Basu and team will implement advanced instrumental variable methods on data provided to them by Mayo to look at treatment effect heterogeneity between branded and generic products.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Devine VA IPA - Critical Limb Ischemia.
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 03/04/2019
Sponsor: VA Veterans Health Administration (VHA) Amount: $36000
Abstract
The purpose of this research is to improve surgical amputation level decision making in patients facing dysvascular transmetarsal (TM) amputation so that functional outcome is optimized while ensuring that patient priorities are incorporated into the decision.
Personnel
Devine, Emily E., Principal Investigator, Adjunct Associate 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, DEPARTMENT OF PHARMACY • , Dept Of Pharmacy, eGC1 Preparer, , • Luetjen, Karen H., Budget Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Use of instrumental variable approaches to assess the safety and efficacy of brand-name and generic drugs used to treat hypothyroidism.
Basu, Anirban , Department Of Pharmacy
Award Date: 03/04/2019
Sponsor: Yale University Amount: $46589
Abstract
Dr. Basu and team will implement advanced instrumental variable methods on data provided to them by Mayo to look at treatment effect heterogeneity between branded and generic products.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • , Dept Of Pharmacy, Budget Contact, , • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
MedsForAll - I-Corps Winter Cohort Customer Discovery Training Program.
Stergachis, Andreas S , Department Of Pharmacy
Award Date: 02/28/2019
Sponsor: National Science Foundation (NSF) Amount: $50000
Abstract
MedsForAll is developing a novel ampule medication cartridge-based drug delivery system that leverages an existing medical infrastructure. The ampule medication cartridge is available globally, standardized to universal ISO standards and is already used every day in hospitals, clinics, pharmacies and by patients but requires technical ability for usage. Our autoinjector technology eliminates these technical requirements allowing any patient access to lower cost autoinjector with equal equivalency. This funding opportunity is for customer research only.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • LEE, RICHARD WON, Key Personnel, Fellow, DEPARTMENT OF PHARMACY • Swanson, Shawn A, Key Personnel, Fellow, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, 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
Establishing A Drug Metabolism, Transport, and Pharmacokinetic Knowledgebase for Research, Development, and Use of Anti-infective Drug Products.
Ragueneau-Majlessi, Isabel, Pharmaceutics
Award Date: 02/27/2019
Sponsor: Bill and Melinda Gates Foundation Amount: $239578
Abstract
Prophylaxis and treatment of major infectious diseases often involve combination therapies. Co-infection requires medications indicated for different infections be used concomitantly. Metabolism and transport-based drug-drug interactions (DDIs) among concomitant medications may lead to increased or decreased drug exposure, putting patients at risks of adverse events or loss of efficacy. Understanding and managing such risks is critical for decisions on safe and effective use of anti-infectives under global health setting. The University of Washington Drug Interaction Database (UW DIDB) Program has an extensive experience in analyzing in vitro and clinical data related to drug interactions in humans. A “PBPK DDI Knowledgebase” tailored for global health anti-infective medications can be established using existing knowledge of drug disposition, metabolism and transport information, and can serve as the basis of model-based prediction of DDI risks at different stages of product development and clinical implementation.
Personnel
Ragueneau-Majlessi, Isabelle, Principal Investigator, Clinical Professor - Salaried, PHARMACEUTICS • McFeely, Savannah, Other, PREDOCTORAL RESEARCH ASSOCIATE 2, PCEUT - LIN LAB, PHARMACEUTICS • Yu, Jingjing, Other, RESEARCH SCIENTIST/ENGINEER 4, DIDB, 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
Hendrix PhRMA Stipend.
Veenstra, David , Department Of Pharmacy
Award Date: 02/19/2019
Sponsor: PhRMA Foundation Amount: $37500
Abstract
The objectives of this study are to model patient outcomes for performance assessment of ML-based algorithms for detection of BC and to survey radiologists on the attributes of an ML-based diagnostic tool that would allow them to accept its use.
Personnel
Veenstra, David, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Luetjen, Karen H., eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Hendrix, Nathaniel, Application PI, Graduate Research Student Assistant (NE H UAW ASE), DEPARTMENT OF PHARMACY
Population-based Interventions to Improve Behavioral Health in a Tribal Healthcare System.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 02/13/2019
Sponsor: Southcentral Foundation Amount: $88808
Abstract
Based on the recommendations of the ISPOR Special Task Force (STF) on Value Assessment Frameworks, we outline a research agenda that builds on conventional cost-effectiveness analysis (CEA) with the aim of implementing “Augmented” CEA (ACEA), by considering additional and novel elements of value. This policy research project will narrow this agenda to three key topics based on input from the Review Committee, STF report members, and discussants. The key objective is to prepare and disseminate three policy papers that can help to advance the use of ACEA.
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, PHARMACEUTICS • Thornton, Timothy A., Key Personnel, Associate Professor, BIOSTATISTICS • Trinidad, Susan B, Key Personnel, Research Scientist/engineer 4, BIOETHICS & HUMANITIES • Calamia, Justina C., 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
PBPK prediction of ontogeny mediated alteration in hepatic drug elimination.
PRASAD, BHAGWAT , Pharmaceutics
Award Date: 02/09/2019
Sponsor: National Institute of Child Health and Human Development (NICHD) Amount: $316428
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, Acting Assistant Professor, PHARMACEUTICS • Whittington, Dale, Other, Research Scientist/engineer 3, MEDICINAL CHEMISTRY • Unadkat, Jashvant D, Co-Investigator, Professor, PHARMACEUTICS • Eng, Matthew N., Administrative Contact, Administrator, PHARMACEUTICS • Chau, Alvin, Budget Contact, Budget/fiscal Analyst Lead, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, Program Operations Specialist, PHARMACEUTICS • Eng, Matthew N., Budget Preparer, Administrator, PHARMACEUTICS
Non-canonical Androgen Metabolism.
PRASAD, BHAGWAT , Pharmaceutics
Award Date: 01/16/2019
Sponsor: VA Puget Sound Health Care System (VAPSHCS) Amount: $20988
Abstract
Naveen Neradugomma will work as Research Associate for Dr. Elahe Mosaghel’s VA Program 821 Biomed Lab study entitled “Non-canonical Androgen Metabolism” and perform studies to determine tissue content of steroidogenic enzymes and steroids in benign and tumor prostate tissue samples. The samples provided by UW GU Biorepository under a UW IRB approved program (UW PI: Bhagwat Prasad) will be used to determine if tissue content of these enzymes associates with presence of the expected/canonical steroids. If not, it would suggest these enzymes may have a non-canonical effect on tumor behavior.
Personnel
Prasad, Bhagwat, Principal Investigator, Assistant Professor without Tenure, PHARMACEUTICS • Neradugomma, Naveen, Key Personnel, 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
RPPR Year 1_Hu R01_A1 Prime Boost.
HU, SHIU-LOK , Pharmaceutics
Award Date: 01/09/2019
Sponsor: National Institutes of Health (NIH) Amount: $891161
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 • Hu, Shiu-Lok, Other, RESEARCH SCIENTIST/ENGINEER-SENIOR, Hu Lab - PRIMA, REGIONAL PRIMATE CTR • Cleveland, Bradley R., Other, RESEARCH SCIENTIST/ENGINEER 3, PCEUT - HU LAB, PHARMACEUTICS • Guo, Wenjin, Other, RESEARCH SCIENTIST/ENGINEER 3, PCEUT - HU LAB, PHARMACEUTICS • Lee, Kelly K., Co-Investigator, Associate Professor, MEDICINAL CHEMISTRY • 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
Implementing Augmented Cost-Effectiveness Analysis: Challenges and Next Steps.
GARRISON, LOUIS P , Department Of Pharmacy
Award Date: 01/08/2019
Sponsor: PhRMA Foundation Amount: $100000
Abstract
Based on the recommendations of the ISPOR Special Task Force (STF) on Value Assessment Frameworks, we outline a research agenda that builds on conventional cost-effectiveness analysis (CEA) with the aim of implementing “Augmented” CEA (ACEA), by considering additional and novel elements of value. This policy research project will narrow this agenda to three key topics based on input from the Review Committee, STF report members, and discussants. The key objective is to prepare and disseminate three policy papers that can help to advance the use of ACEA.
Personnel
Garrison, Louis P, Principal Investigator, Professor Emeritus, 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
Functional Dynamics of P-glycoprotein.
ATKINS, WILLIAM M. , Medicinal Chemistry
Award Date: 01/02/2019
Sponsor: National Institutes of Health (NIH) Amount: $299338
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 • Kwon, Hye Won, Other, Research Scientist/engineer 3, 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 • Unadkat, Jashvant D, Co-Investigator, Professor, PHARMACEUTICS • Kanov, Jeanine M., Administrative Contact, Administrator, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Budget Contact, Administrator, MEDICINAL CHEMISTRY • Kanov, Jeanine M., eGC1 Preparer, Administrator, MEDICINAL CHEMISTRY
PK and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants.
Hebert, Mary F , Department Of Pharmacy
Award Date: 12/21/2018
Sponsor: Duke University Amount: $79000
Abstract
This study is designed to evaluate the pharmacokinetics and safety of drugs in the breast milk.
Personnel
Principal Investigator, Professor, DEPARTMENT OF PHARMACY, mhebert@uw.edu • Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY, kimurm@uw.edu • Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY, luetjen@u.washington.edu • eGC1 Preparer, , , dpgrants@uw.edu
A Pragmatic Trial to Improve Colony Stimulating Factor Use in Cancer.
SULLIVAN, SEAN , Department Of Pharmacy
Award Date: 12/19/2018
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $80339
Abstract
Pragmatic Clinical Studies and Large Simple Trials to Evaluate Patient-Centered Outcomes-- UW will participate as a subrecipient to the Fred Hutch.
Personnel
Principal Investigator, Professor, DEPARTMENT OF PHARMACY, sdsull@u.washington.edu • Key Personnel, Research Assistant Professor, DEPARTMENT OF PHARMACY, abansal@uw.edu • Key Personnel, Professor, DEPARTMENT OF PHARMACY, jmccune@u.washington.edu • Key Personnel, Asst Professor Without Tenure, DEPARTMENT OF MEDICINE, bhg@u.washington.edu • Administrative Contact, Administrator, DEPARTMENT OF PHARMACY, wazzu@u.washington.edu • Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY, luetjen@uw.edu • eGC1 Preparer, Program Operations Specialist, DEPARTMENT OF PHARMACY, ehlers59@uw.edu
The University of Washington, School of Pharmacy Research Affiliates Program on Transporters (UWRAPT).
UNADKAT, JASHVANT D , Pharmaceutics
Award Date: 12/12/2018
Sponsor: Millennium Pharmaceuticals, 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
Principal Investigator, Professor, PHARMACEUTICS, jash@u.washington.edu • Administrative Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS, royall@uw.edu • Budget Contact, Administrator, PHARMACEUTICS, mneng@uw.edu • eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu
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: 12/07/2018
Sponsor: University of Utah Amount: $269679
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
Principal Investigator, Professor, DEPARTMENT OF PHARMACY, hswhite@uw.edu • Key Personnel, Research Scientist/engineer-senior, DEPARTMENT OF PHARMACY, mhaliski@uw.edu • Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY, kimurm@uw.edu • Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY, luetjen@uw.edu • eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY, luetjen@uw.edu • Budget Preparer, , , dpgrants@uw.edu
Beat MS.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 12/03/2018
Sponsor: Benaroya Research Institute at Virginia Mason Amount: $30368
Abstract
Dr. Carlson, with Dr. Bansal, will perform an economic analysis alongside of the clinical trial, BEAT-MS. Specifically, he will be responsible for the study design, data analysis, and interpretation of data for the within trial economic analyses and the development, analysis and interpretation of the simulation model for the long-term economic analysis. He will participate the development of the protocol, study materials, and data collection forms related to the CEA. He will advise on all project aims from the health economics perspective.
Personnel
Principal Investigator, Associate Professor, DEPARTMENT OF PHARMACY, carlsojj@uw.edu • Key Personnel, Assistant Professor, DEPARTMENT OF PHARMACY, abansal@uw.edu • Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY, luetjen@uw.edu • Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY, luetjen@u.washington.edu • eGC1 Preparer, , , luetjen@uw.edu
Impact of Malaria Co-Infection on HIV Vaccination.
HU, SHIU-LOK , Pharmaceutics
Award Date: 11/28/2018
Sponsor: University of Miami Amount: $375939
Abstract
The University of Washington subcontract will be responsible for coordination and management of the nonhuman primate studies, including tissue processing and biological assays, in collaboration with Dr. Manuzak. The studies will include:•?animal study coordination, tissue sample processing, flow cytometry, viral load, ELISA, and luminex assays•?malaria infections, SHIV vaccinations and challenge•?characterization of mucosal and systemic immune responses•?evaluation of SHIV-specific T cell responses in the blood and mucosa of nonhuman primates.
Personnel
Principal Investigator, Professor, PHARMACEUTICS, hus@uw.edu • Other, RESEARCH SCIENTIST/ENGINEER 1, PCEUT - KLATT LAB, PHARMACEUTICS, ecoronad@uw.edu • Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu • Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu • eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu
Persistent modulation of microbiota to enhance HIV vaccination.
Hu, Shiu-Lok , Pharmaceutics
Award Date: 11/26/2018
Sponsor: University of Miami Amount: $263550
Abstract
The University of Washington subcontract will be responsible for coordination and management of the nonhuman primate studies, including tissue processing and biological assays, in collaboration with Dr. Klatt. The studies will include: •animal study coordination, tissue sample processing, flow cytometry, ELISA, and luminex assays. •vaccinations and evaluation of the SIV-specific adaptive mucosal and systemic adaptive immune responses. •measuring and characterizing vaccine and SIV-specific T cell responses in the blood and mucosa of nonhuman primates •investigating mucosal homing markers as a surrogate marker for induction of mucosal T cell responses in the gut or lung •developing and qualifying assays for measuring HIV –specific T cell responses including surrogate markers for mucosal homing and lytic function using samples from HIV infected patients.
Personnel
Principal Investigator, Professor, PHARMACEUTICS, hus@uw.edu • Other, RESEARCH SCIENTIST/ENGINEER 1, PCEUT - KLATT LAB, PHARMACEUTICS, ecoronad@uw.edu • Other, PREDOCTORAL RESEARCH ASSOCIATE 2, School of Pharma, PHARMACEUTICS, atgustin@uw.edu • Other, Research Scientist/Engineer 1 (NE S 6), MICROBIOLOGY, tbl95@uw.edu • Co-Investigator, Professor without Tenure, MICROBIOLOGY, fullerdh@uw.edu • Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu • Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu • eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu
Cost Effectiveness Analysis of Stem Cell Transplant in Older MDS Patients.
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 11/06/2018
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $11625
Abstract
Dr. Bansal will serve as consortium principal investigator on Dr. Ramsey’s Ancillary cost effectiveness analysis study.
Personnel
Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY, abansal@uw.edu • Administrative Contact, Administrator, DEPARTMENT OF PHARMACY, jbrase@u.washington.edu • Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY, luetjen@u.washington.edu • eGC1 Preparer, Program Operations Specialist, DEPARTMENT OF PHARMACY, ehlers59@uw.edu
Role of epithelial cell intrinsic vitamin A metabolism in regulating immune homeostasis in the gut.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 11/01/2018
Sponsor: Brown University Amount: $39262
Abstract
For the studies proposed in this application, throughout the funding period we will conduct all the labeled and unlabeled retinoic acid, retinol, retinyl ester and RBP4 measurements in the biological samples collected using our validated and sensitive liquid chromatography mass spectrometry methods, to aid in determining the role of the microbiome in regulating retinoid metabolism and vitamin A homeostasis and in understanding the role of Rdh7 in retinoid biosynthesis. 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 and aid in interpretation of the biochemistry of retinoid metabolism.
Personnel
Principal Investigator, Associate Professor, PHARMACEUTICS, ni2@u.washington.edu • Other, Research Scientist/engineer 2, PHARMACEUTICS, • 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, PHARMACEUTICS, royall@uw.edu
Impact of Cannabis on Inflammation and Viral Persistence in Treated HIV/SIV.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 10/31/2018
Sponsor: University of Miami Amount: $195720
Abstract
pending
Personnel
Principal Investigator, Professor, PHARMACEUTICS, ni2@uw.edu • Other, PREDOCTORAL RESEARCH ASSOCIATE 2, PCEUT - KLATT LA, PHARMACEUTICS, rycheu@uw.edu • Co-Investigator, Professor without Tenure, DEPARTMENT OF MEDICINE, acollier@uw.edu • Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu • Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu • eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu
Role of genetics on tobacco cessation in Alaska Native/American Indian Community.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 10/26/2018
Sponsor: Southcentral Foundation Amount: $5539
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
Principal Investigator, Professor, PHARMACEUTICS, thummel@u.washington.edu • Other, Research Scientist/engineer 4, BIOETHICS & HUMANITIES, sbtrini@uw.edu • Administrative Contact, Administrator, PHARMACEUTICS, mneng@uw.edu • Budget Contact, Administrator, PHARMACEUTICS, mneng@uw.edu • eGC1 Preparer, Administrator, PHARMACEUTICS, mneng@uw.edu • Budget Preparer, Administrator, PHARMACEUTICS, mneng@uw.edu
BMT CTN Ancillary Cost Effectiveness Analysis.
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 10/17/2018
Sponsor: Fred Hutchinson Cancer Research Center (FHCRC) Amount: $14369
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
Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY, abansal@uw.edu • Budget Contact, Grants And Contracts Manager/specialist, DEPARTMENT OF PHARMACY, luetjen@uw.edu • eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY, luetjen@uw.edu
Natural Product-Drug Interaction Research: The Roadmap to Best Practices.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 10/12/2018
Sponsor: Washington State University (WSU) Amount: $284958
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
Principal Investigator, Professor, PHARMACEUTICS, thummel@u.washington.edu • Other, Senior Fellow, PHARMACEUTICS, • Other, Research Scientist/engineer 3, PHARMACEUTICS, brianp8@u.washington.edu • Co-Investigator, Professor Emeritus, PHARMACEUTICS, ds@uw.edu • Co-Investigator, Professor, PHARMACEUTICS, jash@u.washington.edu • Co-Investigator, Professor, MEDICINAL CHEMISTRY, rettie@uw.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, PHARMACEUTICS, royall@uw.edu
Administrative Supplement - Natural Product-Drug Interaction Research: The Roadmap to Best Practices.
Thummel, Kenneth E. , Pharmaceutics
Award Date: 10/12/2018
Sponsor: Washington State University (WSU) Amount: $251133
Abstract
The University of Washington subcontract under Dr. Jashvant Unadkat will be responsible for studies evaluating the role of cannabinoids as perpetrators of drug interactions, including: conducting the in vitro inhibition studies using cannabis brownies and the major metabolites of tetrahydrocannabinol (THC), 11-hydroxy tetrahydrocannabinol (11-OH-THC) and 11-nor-carboxy tetrahydrocannabinol (COOH-THC), bioanalysis of plasma and urine samples of the cannabis clinical study (that will be conducted at Johns Hopkins Univ), as well as pharmacokinetic analysis of the clinical study data; and developing and validating LC-MS/MS methods to quantify the cannabinoids as well as all CYP probes and their respective metabolites for the in vitro and clinical study samples.
Personnel
Principal Investigator, Professor, PHARMACEUTICS, thummel@uw.edu • Other, Senior Fellow, PHARMACEUTICS, nmaharao@uw.edu • Co-Investigator, Professor, PHARMACEUTICS, jash@uw.edu • Administrative Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu • Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu • eGC1 Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS, royall@uw.edu
Use of instrumental variable approaches to assess the safety and efficacy of brand-name and generic drugs used to treat hypothyroidism.
Basu, Anirban , Department Of Pharmacy
Award Date: 10/03/2018
Sponsor: Yale University Amount: $34942
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
Principal Investigator, Professor, PHARMACEUTICS, thummel@u.washington.edu • Other, Senior Fellow, PHARMACEUTICS, • Other, Research Scientist/engineer 3, PHARMACEUTICS, brianp8@u.washington.edu • Co-Investigator, Professor Emeritus, PHARMACEUTICS, ds@uw.edu • Co-Investigator, Professor, PHARMACEUTICS, jash@u.washington.edu • Co-Investigator, Professor, MEDICINAL CHEMISTRY, rettie@uw.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, PHARMACEUTICS, royall@uw.edu
Functional Dynamics of Cytochrome P4503A4.
Atkins, William M. , Medicinal Chemistry
Award Date: 10/01/2018
Sponsor: National Institutes of Health (NIH) Amount: $496257
Abstract
Cytochrome P450s, including the isoform CYP3A4, dominate drug metabolism and are responsible for many drug-drug interactions that cause toxicity, side effects, or death. Cytochrome P450s exhibit complex kinetics and allosteric properties that make prediction of drug metabolism difficult on the basis of in vitro experiments. This proposal aims to understand the biophysical and dynamic behavior of CYPS in order to better predict drug interactions and drug clearance.
Personnel
Principal Investigator, Professor, MEDICINAL CHEMISTRY, winky@uw.edu • Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY, jeaninek@uw.edu • Budget Contact, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY, eriklee@uw.edu • eGC1 Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY, jeaninek@uw.edu
Genentech Fellowship.
VEENSTRA, DAVID , Department Of Pharmacy
Award Date: 10/01/2018
Sponsor: Genentech, Inc. Amount: $259517
Abstract
Genentech would like to support a Two-Year Fellowship Program in Health Economics and Outcomes Research (HEOR) through the University and its Department of Pharmacy.
Personnel
Principal Investigator, Professor, DEPARTMENT OF PHARMACY, veenstra@uw.edu • Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY, wazzu@uw.edu • Budget Contact, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY, luetjen@uw.edu • eGC1 Preparer, , , dpgrants@uw.edu