Grants and Awards

One-year period ending September 30, 2022. Click on a title to read more.
Awards information as defined in UW SAGE.
Circulating hydrogen sulfide, diabetes and diabetes-related cardiovascular disease.
TOTAH, RHEEM A. , Medicinal Chemistry
Award Date: 09/16/2022
Sponsor: National Institutes of Health (NIH) Amount: $673106
Abstract
Type 2 diabetes has reached epidemic proportions world-wide and carries a high burden of cardiovascular morbidity and mortality. Understanding potentially modifiable mechanisms that may influence the development of these multifactorial diseases has a substantial public health impact. This application seeks to identify modifiable factors, namely Hydrogen sulfide (H2S) and methylated hydrogen sulfide (MeSH), associated with risks of incident diabetes and diabetes-associated cardiovascular disease (CVD). Hydrogen sulfide (H2S) is one of three gasotransmitters, along with CO and NO, that are crucial for cell signaling and cell function. H2S acts as a vasodilator to improve cardiac function and protect against cardiac injury. Most pertinent to this proposal is the relevance of H2S to development of diabetes. Patients with type 2 diabetes showed a progressive reduction in the plasma H2S levels which was accompanied by poor glycemic control. More importantly, a reduction in the plasma H2S levels was found to be related to a history of cardiovascular disease in patients with type 2 diabetes. Compounds that release H2S and therefore increase systemic concentrations attenuated nephropathy in rats. The overall reduction in plasma H2S in diabetic patients may have implications in the pathophysiology of cardiovascular disease in diabetic patients. Guided by published animal studies and human data we hypothesize that higher plasma H2S levels are associated with lower risks of incident diabetes and diabetes-associated cardiovascular disease. To test this hypothesis, we will measure circulating H2S levels in humans, and in Aim 1, comprehensively examine H2S association with clinical outcomes, with a focus on type 2 diabetes. This is the largest examination of the association of H2S with health and disease in humans. Importantly, we supplement these observational associations with functional studies in Aim 2 that will experimentally investigate the molecular mechanism of H2S cardiac protection and discover the pathways regulating H2S biosynthesis and metabolism under stressors observed during diabetes.
Personnel
Totah, Rheem A., Principal Investigator, Associate Professor, MEDICINAL CHEMISTRY • Zeigler, Maxwell Bertrand, Other, Research Scientist/Engineer 3 (E S 8), MEDICINAL CHEMISTRY • Carter, Ashley A, Other, Research Coordinator (E S 8), DEPARTMENT OF MEDICINE • Jensen, Paul N, Other, RESEARCH SCIENTIST/ENGINEER 4, Department of Medic, DEPARTMENT OF MEDICINE • Kannan, Nithya, Other, Research Consultant (E S 7), BIOSTATISTICS • McCrain, Cynthia, Other, MANAGER OF PROGRAM OPERATIONS, Department of Medic, DEPARTMENT OF MEDICINE • Enright, Erika A., Other, RESEARCH COORDINATOR, Biostatistics Dept: CHSCC Re, BIOSTATISTICS • Sitlani, Colleen M., Other, RESEARCH SCIENTIST/ENGINEER 4, Department of Medic, DEPARTMENT OF MEDICINE • Gharib, Sina A., Co-Investigator, Professor WOT, DEPARTMENT OF MEDICINE • Sotoodehnia, Nona, Co-Investigator, Associate Professor without Tenure, DEPARTMENT OF MEDICINE • Lemaitre, Rozenn N., Multiple PI, Research Associate Professor, DEPARTMENT OF MEDICINE • Kanov, Jeanine M., Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, 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 • Kanov, Jeanine M., Budget Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
Washington Entrepreneurial Research Evaluation and Commercialization Hub.
HO, RODNEY J.Y. , Pharmaceutics
Award Date: 09/06/2022
Sponsor: National Institutes of Health (NIH) Amount: $994469
Abstract
The overarching goal of the partnership between NIH and the University of Washington (UW) Entrepreneurial Research Evaluation and Commercialization Hub (referred to as WE-REACH) is to facilitate and accelerate the transformation of health research innovations into products and services that address unmet medical needs. We will accomplish this through the following aims: 1. Develop innovative, synergistic and integrated infrastructure and implementation systems2. Identify the most promising technologies and increase their impact through the provision of gap funding, resources and mentoring (in business, marketing, networking and assessing funding) for proof-of-concept and product definition3. Fuel the formation of new biotech, pharma and medical device companies and assist in pathways to a self-sustaining structure 4. Train the next generation of biomedical-entrepreneurs to lead these ventures.
Personnel
Ho, Rodney J.Y., Principal Investigator, Professor, PHARMACEUTICS • Stergachis, Andreas S, Key Personnel, Professor, DEPARTMENT OF PHARMACY • Patel, Shwetak Naran, Key Personnel, Professor, COMPUTER SCIENCE & ENG • Baker, David, Key Personnel, PROFESSOR, Biochemistry, BIOCHEMISTRY • Disis, Mary L., Key Personnel, Professor without Tenure, DEPARTMENT OF MEDICINE • Wills, Fiona L, Key Personnel, DIRECTOR, CoMotion, COMOTION • Sun, Tong, Key Personnel, DIRECTOR, DEANS: Institute of Translational Health, ITHS • Ingram, Jonathan B, Other, Program Operations Specialist (E S 7), PHARMACEUTICS • Hartman, Matthew H, Other, Program Operations Specialist (E S 7), PHARMACEUTICS • Butler, Terri Larson, Other, Program Operations Specialist (E S 9), PHARMACEUTICS • Ransom, Scott, Other, MANAGER OF PROGRAM OPERATIONS, Computer Science &, COMPUTER SCIENCE & ENG • Fukuda, Yuichi, Other, Program Operations Specialist (E S 7), PHARMACEUTICS • Jonsson, Christine Anne, Administrative Contact, MANAGER OF PROGRAM OPERATIONS, Department of Medic, DEPARTMENT OF MEDICINE • Fukuda, Yuichi, Budget Contact, Program Operations Specialist (E S 7), PHARMACEUTICS • Fukuda, Yuichi, eGC1 Preparer, Program Operations Specialist (E S 7), PHARMACEUTICS • Fukuda, Yuichi, Advance Preparer, Program Operations Specialist (E S 7), PHARMACEUTICS
Pharmacology of Drugs of Abuse During Pregnancy.
UNADKAT, JASHVANT D , Pharmaceutics
Award Date: 08/29/2022
Sponsor: National Institutes of Health (NIH) Amount: $1475139
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 • Isoherranen, Nina, Co-Investigator, Professor, PHARMACEUTICS • Mao, Qingcheng, Co-Investigator, Associate Professor, PHARMACEUTICS • Kelly, Edward J, Co-Investigator, Associate Professor, PHARMACEUTICS • Rubinow, Katya B., Co-Investigator, Associate Professor WOT, DEPARTMENT OF MEDICINE • Amory, John K., Co-Investigator, Professor, DEPARTMENT OF MEDICINE • Kirkpatrick, Leila, Administrative Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, Budget Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, Advance Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS
ThermoFisher Scientific Orbitrap Eclipse with ETD and UVPD.
GUTTMAN, MIKLOS , Medicinal Chemistry
Award Date: 08/29/2022
Sponsor: National Institutes of Health (NIH) Amount: $1184239
Abstract
Mass spectrometry has revolutionized bioanalytical tools to study key questions in biomedical sciences. The School of Pharmacy Mass Spectrometry Center has become a powerhouse in the use of structural mass spectrometry to gain new insights into drug-metabolizing enzymes, host-pathogen interactions, vaccine development strategies, and ways to modulate the immune system. Much of this work has given us new ways to track disease progression and identify novel therapeutics for a variety of diseases. This revised shared instrument proposal seeks to obtain a state-of-the-art mass spectrometer to overcome current limitations imposed by existing instruments and provide a much-needed tool for answering even more challenging and pressing questions in biomedical sciences.
Personnel
Guttman, Miklos, Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Baker, David, Other, PROFESSOR, Biochemistry, BIOCHEMISTRY • Bhardwaj, Gaurav, Other, Assistant Professor, MEDICINAL CHEMISTRY • Atkins, William M., Other, Professor, MEDICINAL CHEMISTRY • Klevit, Rachel E, Other, Professor, BIOCHEMISTRY • Lee, Kelly K., Other, Associate Professor, MEDICINAL CHEMISTRY • Maly, Dustin James, Other, Professor, CHEMISTRY • Kollman, Justin M, Other, Associate Professor, BIOCHEMISTRY • Totah, Rheem A., Other, Associate Professor, MEDICINAL CHEMISTRY • Zheng, Ning, Other, Professor, PHARMACOLOGY • Whittington, Dale, Other, Teaching Associate, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, 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
Identification and quantification of drug-protein adducts by mass spectrometry.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 08/22/2022
Sponsor: National Institutes of Health (NIH) Amount: $433127
Abstract
Unanticipated adverse drug reactions remain a major cause of post marketing withdrawals of drugs and of restricted access to new medications. Adverse drug reactions are often caused by reactive metabolites that form covalent adducts with proteins, but the identity and extent of protein adducts formed is often difficult to predict and characterize. Despite decades of research, current methods are unable to produce a comprehensive and quantitative catalog of xenobiotic protein adducts. This hinders progress in optimizing safety of novel medications and limits our ability to define mechanisms of clinically observed adverse drug reactions. To bridge this gap, we have developed innovative proteomic methods for discovery, characterization and quantification of protein adducts in simple and complex biological matrices. The goal of this proposal is to establish these methods for rapid, reliable and quantitative identification and characterization of drug-protein adducts, and uniquely customize these methods for human adductomics research impacting drug safety assessment. We will focus on covalent protein modifications resulting from metabolic oxidative activation of drugs. We will use a set of model compounds that are known to cause adverse events in patients and form reactive metabolites that likely result in protein adducts. In our aim 1 we will test the hypothesis that the modification masses and chemical characteristics of protein adducts formed by reactive metabolites in recombinant enzyme systems predict adduct formation in more complex systems such as liver microsomes and S9 fractions. Through this work we will optimize our proteomics methods for complex human liver preparations from individual donors. In aim 2 we will test the hypothesis that adduct formation varies quantitatively between individuals and due to differences in metabolic activity and individual genotype. In this aim we will establish quantitative adductomics for individual donors and define the basis for inter-individual variability in drug-protein adduct formation. In aim 3 we will test the hypothesis that human hepatocytes exposed to reactive metabolites generated in situ secrete proteins that have been adducted by the reactive intermediates. In this aim we will establish the in vitro relationship between hepatocyte adductomic burden and secretion of adducted proteins as biomarkers. When completed, the proposed studies will be transformative in integrating novel suite of cutting-edge tools and high-dimensional proteomics data to characterize the deep adductomic profiles of key drugs resulting in adverse drug reactions. The methods developed will enable the assessment and quantification of a broad range of adducts across the human proteome. The results will generate unprecedented insight into mechanisms of enzyme inactivation, liver adductomes formed after exposure to reactive metabolites and quantitative relationships between adduct formation and metabolic activity in the liver. The results may ultimately lead to novel drug discovery approaches that mitigate risk of adverse drug reactions resulting from adduct formation and to development of targeted therapeutic interventions designed to treat adverse drug reactions.
Personnel
Isoherranen, Nina, Principal Investigator, Professor, PHARMACEUTICS • Zelter, Alexander, Co-Investigator, Research Scientist/Engineer-Senior (E S 10), BIOCHEMISTRY • Maccoss, Michael, Co-Investigator, Professor, GENOME SCIENCES • Camp, Alyssa L, Administrative Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Kirkpatrick, Leila, Budget Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, Budget Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS
Characterizing the broad antibody response to HIV superinfection.
LEE, KELLY K., Medicinal Chemistry
Award Date: 08/19/2022
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 • Lidzbarski, Erik August Lee, Advance Preparer, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY
Development of recommendations and policies for genetic variant reclassification.
Veenstra, David , Department Of Pharmacy
Award Date: 08/18/2022
Sponsor: Columbia University Amount: $61278
Abstract
In this supplemental activity, University of Washington will provide guidance and expert advice on assessing the readiness for active safety surveillance.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • ZARAA, SABRA, Other, Graduate Research Student Assistant (NE H 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Personalized Risk-AdaptIve Surveillance strategies in cancEr (PRAISE).
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 08/17/2022
Sponsor: National Institutes of Health (NIH) Amount: $419114
Abstract
This research addresses a significant problem in cancer survivorship care by using novel approaches and developing a practical tool to help resolve the uncertainty that clinicians and patients face when confronted with using new and evolving biomarker technologies to monitor for recurrence after patients have survived their primary cancer. Our holistic approach of applying the decision-making framework to three wide ranging cancer applications will inform both clinical decision-making in these areas and also future policy decisions on research investments with a transparent link between the needs for additional biomarker development and improving population outcomes.
Personnel
Bansal, Aasthaa, Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Basu, Anirban, Co-Investigator, Professor, DEPARTMENT OF PHARMACY • Veenstra, David, Co-Investigator, Professor, DEPARTMENT OF PHARMACY • Heagerty, Patrick J., Co-Investigator, Professor, 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 • Camp, Alyssa L, Budget Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Preparer, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Luetjen, Karen H., Advance Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY
Multistage LC-MSn for automated glycan isomer assignment of glycopeptides.
GUTTMAN, MIKLOS , Medicinal Chemistry
Award Date: 08/17/2022
Sponsor: Protein Metrics Amount: $135685
Abstract
A milieu of complex sugar structures cover of the cells of higher organisms and play critical roles in biology including regulation of host-pathogen interactions and modulating 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 our recent developments in sugar analysis through fragment ion ratio mapping into a software tool developed in partnership with Protein Metrics as part of a phase I NIH small business technology transfer grant. This technology will provide a much-needed tool for understand the role that structural sugars play regulation of the immune response, tumor progression, as well as to the biopharmaceutical community for characterization of the next generation of biotherapeutics
Personnel
Guttman, Miklos, Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Mookherjee, Abhigya, Other, Postdoctoral Scholar, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, 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 • Lidzbarski, Erik August Lee, Advance Preparer, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY
A Nanodrug for the Cure of Metastatic Breast Cancer .
FERRARI, MAURO , Pharmaceutics
Award Date: 08/08/2022
Sponsor: US Army Medical Research and Materiel Command (USAMRMC) Amount: $1530579
Abstract
The Objectives of this application are: 1) to complete GLP safety studies of iNPG-pDox in two animals species in support of an IND filing with the FDA; 2) to secure approval by the US FDA for clinical trials of iNPG-pDox for the treatment of TNBC with visceral metastasis; 3) to perform a Phase I clinical trial to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and other toxicities possibly associated with iNPG-pDox in patients with TNBC visceral metastasis; and 4) to conduct a Phase II clinical trial to evaluate the ORR, efficacy, and safety of iNPG-pDox in TNBC patients. Our central hypothesis is that iNPG-pDox will prove safe and provide long-term survival benefits (disease-free outcomes) in patients, where the drug is able to penetrate the relevant biological barriers and localize treatment on the metastatic lesions – resulting in a breakthrough treatment option for patients with few to no effective alternatives.
Personnel
Ferrari, Mauro, Principal Investigator, Affiliate Professor, PHARMACEUTICS • Ho, Rodney J.Y., Key Personnel, Professor, PHARMACEUTICS • Kirkpatrick, Leila, Administrative Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, Budget Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS
Rat and Canine Microphysiological Systems of the Kidney Proximal Tubule for Chemical Toxicity Screening.
Yeung, Catherine , Department Of Pharmacy
Award Date: 08/03/2022
Sponsor: Nortis, Inc Amount: $218689
Abstract
This project is a collaboration between Nortis Inc. (PI, T. Neumann) and the University of Washington School of Pharmacy (Co-Is, C. K. Yeung and E. J. Kelly). The goal of this application is to develop commercially viable kidney proximal tubule microphysiologic systems (KPT-MPS) using rat and canine proximal tubule epithelial cells (PTECs) that can be used in pre-clinical drug development to identify potential nephrotoxicity.
Personnel
Yeung, Catherine, Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • Zelnick, Leila, Key Personnel, Research Assistant Professor, DEPARTMENT OF MEDICINE • Van Ness, Kirk Peter, Key Personnel, RESEARCH SCIENTIST/ENGINEER 2, PCEUT - KELLY LAB, PHARMACEUTICS • Himmelfarb, Jonathan, Key Personnel, Professor, DEPARTMENT OF MEDICINE • Bammler, Theodor K., Key Personnel, RESEARCH SCIENTIST/ENGINEER-SENIOR, Enviro & Occup, ENVIRO & OCCUP HEALTH • Kelly, Edward J, Multiple PI, Associate Professor, PHARMACEUTICS • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Hormone mediated mechanisms of altered drug metabolism and transport in transgender adults.
Cirrincione, Lauren , Department Of Pharmacy
Award Date: 07/28/2022
Sponsor: National Institutes of Health (NIH) Amount: $187056
Abstract
Worldwide nearly 25 million adults are part of a growing population of transgender people. Many transgender adults undergo hormone therapy as one part of the standard of medical care, but the effect of high dose sex hormone therapy on drug safety and efficacy has not been established. This project aims to evaluate the effect of estradiol treatment on the activities of cytochrome P450 3A and P-glycoprotein activities, two key drug handling proteins, to establish the effect of gender-affirming hormone therapy on drug disposition in transgender adults.
Personnel
Cirrincione, Lauren, Principal Investigator, Assistant Professor, DEPARTMENT OF PHARMACY • Micks, Elizabeth A, Key Personnel, Associate Professor without Tenure, OBGYN/ADMIN • Bansal, Aasthaa, Other, Associate Professor, DEPARTMENT OF PHARMACY • Anawalt, Bradley D, Other, Professor without Tenure, DEPARTMENT OF MEDICINE • Hebert, Mary F, Mentor, Professor, DEPARTMENT OF PHARMACY • Thummel, Kenneth E., Mentor, Professor, PHARMACEUTICS • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Drug, Nucleotide, and Lipid Interactions with P-glycoprotein.
ATKINS, WILLIAM M. , Medicinal Chemistry
Award Date: 07/28/2022
Sponsor: National Institutes of Health (NIH) Amount: $318976
Abstract
This proposal aims to understand fundamental mechanisms of the efflux transporter P-glycoprotein. P-glycoprotein pumps drugs and toxins from cells and plays a critical role in drug-drug and drug-food interactions. Increased mechanistic understanding of P-glycoprotein will facilitate prediction of drug-drug interactions and could aid in the development of new drugs.
Personnel
Unadkat, Jashvant D, Principal Investigator, Professor, PHARMACEUTICS • Isoherranen, Nina, Co-Investigator, Professor, PHARMACEUTICS • Mao, Qingcheng, Co-Investigator, Associate Professor, PHARMACEUTICS • Kelly, Edward J, Co-Investigator, Associate Professor, PHARMACEUTICS • Rubinow, Katya B., Co-Investigator, Associate Professor WOT, DEPARTMENT OF MEDICINE • Amory, John K., Co-Investigator, Professor, DEPARTMENT OF MEDICINE • Kirkpatrick, Leila, Administrative Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, Budget Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, Advance Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS
Lipid Bilayer Remodeling and Protein Intermediates During Membrane Fusion.
LEE, KELLY K. , Medicinal Chemistry
Award Date: 07/26/2022
Sponsor: National Institutes of Health (NIH) Amount: $597847
Abstract
Protein-mediated membrane fusion is a fundamental process that is essential for biological functions as wide ranging as gamete fertilization, formation of placenta, synaptic vesicle trafficking, tissue development, mitochondrial function, and enveloped virus infection. Despite its significance, little is understood at a mechanistic and structural level regarding how specialized fusion protein machinery and membranes interact in order to go from a prefusion to activated fusogenic to fusion pore formation state. Here cryo-electron microscopy and structural mass spectrometry will be used to study membrane fusion in two highly divergent enveloped viruses, thus providing new insights into how very different protein machines accomplish similar physical functions of merging two distinct membranes into one.
Personnel
Lee, Kelly K., Principal Investigator, Associate Professor, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, 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 • Kanov, Jeanine M., Budget Preparer, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY
Allergan Fellowship Program in Pharmacoeconomics (Baldwin).
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 07/21/2022
Sponsor: AbbVie Inc. Amount: $239243
Abstract
The University of Washington will utilize a previously developed model (RISE) evaluating the cost-utility of population screening for three CDC Tier-1 genomic applications (HBOC, FH, and Lynch) to assess the cost-utility of variant reinterpretation. The focus of the analysis will be reinterpretation of VUSs in HBOC vs. no variant reinterpretation. Scenario analyses will be conducted assessing different reinterpretation costs and frequencies. Assessment of FH and Lynch reinterpretation will be incorporated as feasible.The investigators will lead the development of a manuscript describing the analysis, results, and interpretation, in collaboration with investigators at Columbia and participating members of the RISE modeling consortium.
Personnel
Veenstra, David, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Guzauskas, Greg, Other, Research Scientist/Engineer 4 (E S 9), DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Hayes, Lori T, eGC1 Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICIN • Hayes, Lori T, Budget Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICIN • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Allergan Fellowship Program in Pharmacoeconomics (Kim).
DEVINE, EMILY E. , Department Of Pharmacy
Award Date: 07/21/2022
Sponsor: AbbVie Inc. Amount: $239243
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 • Hayes, Lori T, eGC1 Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICINE
Impact of Chronic Seizures on Neuropsychiatric Comorbidities in AD-Associated Models.
HALISKI, MELISSA , Department Of Pharmacy
Award Date: 07/13/2022
Sponsor: National Institute of Mental Health (NIMH) Amount: $388750
Abstract
Patients with Alzheimer’s disease (AD) experience seizures, although these events are commonly non-convulsive in nature and thus potentially missed. Despite this, little is known regarding the direct long-term impact of untreated seizures on disease progression in patients with AD. This study will directly define whether chronic seizures age-dependently aggravate cognitive and neuropsychiatric comorbidities of AD.
Personnel
Haliski, Melissa, Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Smith, Carole L., Other, RESEARCH SCIENTIST/ENGINEER 2, Neurology: Dr. Jaya, NEUROLOGY • Jayadev, Suman, Other, ASSOC PROFESSOR WITHOUT TENURE, Neurology: Neuroge, NEUROLOGY • Zierath, Dannielle, Other, Research Scientist/Engineer 3 (E S 8), NEUROLOGY • Knox, Kevin, Other, Research Scientist/Engineer 1 (E S 6), 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Interactions between metabolism, transport, and toxicity of benzalkonium chlorides.
XU, LIBIN , Medicinal Chemistry
Award Date: 07/12/2022
Sponsor: Amount: $463606
Abstract
Benzalkonium chlorides (BACs) are widely used as disinfectants and preservatives in cleaning products (Lysol, Clorox, hand sanitizer), medical products (eye drops and nasal spray), consumer products (cosmetics and personal care), and food processing industries, suggesting humans may be systemically exposed to BACs through a wide range of routes. Indeed, our preliminary study found that close to 50 of 100 random human plasma samples contain detectable levels of BACs, suggesting BACs can indeed be absorbed. The ongoing COVID-19 pandemic has led to greatly increased use of BAC-containing disinfectants, which is concerning given accumulating evidence in respiratory, developmental, reproductive, and neurological toxicities inflicted by BACs in rodents and BAC-induced disruption of cholesterol and lipid homeostasis in mice. However, there is a lack of knowledge on the metabolism, transport, and biological consequences of BACs in humans. We hypothesize that toxicities of BACs in liver and kidney are dependent on the activities of their metabolizing and transporting proteins. In this project, we will first characterize pathways of metabolism, transport, and toxicity of BACs in 2D cell culture and 3D microphysiological systems (“organ-on-a-chip”). We will then assess BAC exposure levels and correlate the exposure levels with sterol, lipid, and renal function biomarkers in humans.
Personnel
Xu, Libin, Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Zhang, Rutan, Fellow, Senior Fellow, MEDICINAL CHEMISTRY • Seguin, Ryan Patrick, Fellow, Senior Fellow Trainee, MEDICINAL CHEMISTRY • Van Ness, Kirk Peter, Other, RESEARCH SCIENTIST/ENGINEER 2, PCEUT - KELLY LAB, PHARMACEUTICS • Macdonald, James, Other, RESEARCH SCIENTIST/ENGINEER 3, Enviro & Occup Heal, ENVIRO & OCCUP HEALTH • Thompson, Brice D, Other, Student Assistant (NE H), PHARMACEUTICS • Rettie, Allan E., Co-Investigator, Professor, MEDICINAL CHEMISTRY • Wang, Joanne, Co-Investigator, Professor, PHARMACEUTICS • Kelly, Edward J, Co-Investigator, Associate Professor, PHARMACEUTICS • Lin, Yvonne S., Co-Investigator, Associate Professor, PHARMACEUTICS • Kanov, Jeanine M., Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, 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
Value-based Formulary-Essentials: Testing and Expanding on Value in Prescription Drug Benefit Design.
SULLIVAN, SEAN , Department Of Pharmacy
Award Date: 07/12/2022
Sponsor: Kaiser Permanente Washington Health Research Institute Amount: $17208
Abstract
Dr. Sullivan will provide expertise in effective engagement and dissemination of study results to payersand purchasers, and will be available to meet 1-2 times per month to discuss study progress.
Personnel
Sullivan, Sean, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Chen, Yilin, 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Landscape analysis: Sentinel site readiness for Maternal Immunization Active Safety Surveillance in LMIC - Supplemental Project”.
STERGACHIS, ANDREAS S , Department Of Pharmacy
Award Date: 07/12/2022
Sponsor: Tulane University Amount: $26587
Abstract
In this supplemental activity, University of Washington will provide guidance and expert advice on assessing the readiness for active safety surveillance.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • ZARAA, SABRA, Other, Graduate Research Student Assistant (NE H 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Pharmacovigilance system strengthening in MTaPS supported countries.
STERGACHIS, ANDREAS S , Department Of Pharmacy
Award Date: 07/07/2022
Sponsor: Management Sciences for Health (MSH) Amount: $83745
Abstract
This project aims to ensure that the pharmacovigilance (PV) component of the regulatory systems strengthening work of MTaPS (Medicines Technologies and Pharmaceutical System) is promptly and effectively carried out to support improvements in health system performance in low- and middle-income countries, and that pharmacovigilance activities are fully implemented to ensure appropriate use of safe, effective, quality assured, and affordable essential medicines.
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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Structural and dynamic traits underlying phenotypic variation in HIV-1 Env.
LEE, KELLY K. , Medicinal Chemistry
Award Date: 06/21/2022
Sponsor: National Institutes of Health (NIH) Amount: $531081
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
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: 06/14/2022
Sponsor: University of Utah Amount: $557432
Abstract
The kainic acid (KA)-induced status epilepticus (SE) model in rats is an etiologically-relevant animal model of epileptogenesis. Just as in patients, who develop temporal lobe epilepsy (TLE) following an SE event, this rat model of KA-induced SE very closely recapitulates many of the clinical and pathological characteristics of human TLE that arise following SE or another neurological insult. Spontaneous recurrent seizures in TLE can present after a latent period following a neurological insult (TBI, SE event, viral infection, etc.). These seizures often present as complex focal seizures that secondarily generalize, and are resistant to currently available anti-seizure drugs. All of these clinical characteristics 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 (Hellier et al., 1998). Rats that have undergone excitotoxin-induced SE demonstrate TLE-associated behavioral comorbidities, including increased anxiety-like behaviors in an open field (Suleymanova et al, 2016) and increased behavioral hyperexcitability (Rice et al, 1998). Thus, the KA-SE model in Sprague Dawley rats provides an appropriate platform to evaluate the impact of an interventional treatment on the acute neurological insult and epileptogenic process. This study will evaluate the effect of early and sub-chronic treatment with promising investigational antiseizure compounds administered to the post KA-induced SE model of epileptogenesis in male Sprague Dawley rats to determine whether the treatment modifies the onset of spontaneous recurrent seizures; i.e., epilepsy is delayed or prevented. Further, this study will determine whether administration of the investigational agent can attenuate behavioral comorbidities of epilepsy, including spatial learning and memory, anxiety-like behaviors, and hyperexcitability.
Personnel
White, Harold Steve, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Guignet, Michelle, Key Personnel, Postdoctoral Scholar, DEPARTMENT OF PHARMACY • Haliski, Melissa, Multiple PI, Research Scientist/engineer-senior, DEPARTMENT OF PHARMACY • Camp, Alyssa L, Administrative Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Hayes, Lori T, eGC1 Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICIN • Luetjen, Karen H., Advance Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Novel Therapeutic Approaches for the Prevention of Drug Resistant Epilepsy.
GUIGNET, MICHELLE , Department Of Pharmacy
Award Date: 06/14/2022
Sponsor: American Epilepsy Society (AES) Amount: $53770
Abstract
Approximately 30-40% of patients with epilepsy cannot achieve seizure freedom with their antiseizure drug (ASD) therapy. Those patients who cannot get control of their seizures often suffer from other conditions such as depression, anxiety, or cognitive decline. Furthermore, uncontrolled epilepsy can lead to a significantly greater risk of sudden unexplained death in epilepsy. It is imperative that we find novel therapeutic strategies for the prevention of drug-resistant epilepsy (DRE). Data from humans and animal models suggest that multiple factors may contribute to DRE, however, the best predictor is whether a patient responds to their first prescribed ASD. What remains to be addressed, is whether certain ASD’s are more likely to lead to drug resistance over others. This proposal will take advantage of clinically relevant approaches to address wither early intervention with an effective ASD will prevent the development of drug resistance in an animal model of epilepsy. Ultimately, these studies will inform whether the initial selection of an ASD can contribute to drug-resistance, as well as identify novel approaches that can prevent it altogether. Ultimately, this study will inform clinical decisions that may drastically improve the lives of people with epilepsy.
Personnel
Guignet, Michelle, Principal Investigator, Postdoctoral Scholar, DEPARTMENT OF PHARMACY • Vuong, Jonathan Yee, Key Personnel, Student Assistant (NE H), DEPARTMENT OF PHARMACY • White, Harold Steve, Other, Professor, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Hayes, Lori T, eGC1 Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICIN • Hayes, Lori T, Budget Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICINE
Mechanisms of IgM mediated activation of the complement system.
GUTTMAN, MIKLOS , Medicinal Chemistry
Award Date: 06/13/2022
Sponsor: National Institutes of Health (NIH) Amount: $484415
Abstract
Antibodies are an integral part of the adaptive immune system and have become the major scaffold for modern biotherapeutics. Immunoglobulin (IgM) is the first antibody made in response to an infection and are present as natural antibodies that are critical for immunity during the early stages of development. Despite their critical importance, the structure of IgMs and how they mediate immune activation are poorly understood. The current proposal aims to utilize new structural techniques to unveil the molecular mechanisms of how IgM recognizes antigen and activates the immune system, which will provide critical insight into the development of a new class of biotherapeutics for treatment of cancers, infectious diseases, and autoimmune disorders.
Personnel
Guttman, Miklos, Principal Investigator, Assistant Professor, MEDICINAL CHEMISTRY • Harkewicz, Richard, Other, Research Scientist/Engineer 3 (E S 8), MEDICINAL CHEMISTRY • Kollman, Justin M, Co-Investigator, Associate Professor, BIOCHEMISTRY • Kanov, Jeanine M., Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, 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
AFPE Pre-Doctoral Fellowship in Pharmaceutical Sciences Application.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 06/13/2022
Sponsor: American Foundation for Pharmaceutical Education (AFPE) Amount: $10000
Abstract
The overall objective of Dr. Khor's dissertation is to develop an understanding of how to incorporate health equity considerations into medical decisions. AIM 1: Examine the relationship between the introduction of new oncologic drugs and disparities in health and economic outcomes. AIM 2: Compare the long-term impacts of adopting race-conscious vs. race-neutral prediction algorithms into clinical care on health disparities. AIM 3: Examine the US public’s stated preferences for health equity when confronted with an equity-efficiency tradeoff
Personnel
Carlson, Joshua J., Principal Investigator, Associate Professor, DEPARTMENT OF PHARMACY • Khor, Sara, Fellow, 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Drug Transport Mechanisms at the Blood-CSF Barrier and Effect of Aging.
WANG, JOANNE , Pharmaceutics
Award Date: 06/08/2022
Sponsor: National Institutes of Health (NIH) Amount: $190309
Abstract
Brain disorders, especially age-related neurological diseases, constitute a major public health problem in the developed world. Despite the urging needs for new and more effective drugs to treat brain diseases, development of CNS drugs remains challenging. To exert their therapeutic effects, CNS-targeted drugs must cross the brain-blood barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) and maintain minimal effective concentrations in the brain. The BBB and BCSFB are not only physical barriers but also express a spectrum of multispecific drug transporters to actively remove drugs and other xenobiotics from the brain. The choroid plexus epithelial (CPE) cells forming the BCSFB play an essential role in brain removal of drugs and metabolites through secretion of the CSF and active transport of solutes from the CSF into the blood circulation. Nevertheless, little is known regarding the molecular and cellular mechanisms governing drug transport processes at the BCSFB. Furthermore, the CPE cells are known to show marked morphological and functional changes during aging but it is unknown if these age-dependent changes impact the expression and activity of transporters at the BCSFB. Our laboratory recently developed a live tissue imaging approach in isolated murine choroid plexus to analyze organic anion and cation transport processes in CPE cells. Our preliminary studies suggest that large amphipathic organic anions (OAs) are rapidly cleared from the CSF side into the blood capillary side by a highly functional BCSFB transport system likely consisting of organic anion transporting polypeptides (Oatps) at the apical membrane and multidrug resistance-associated proteins (Mrps) at the basolateral membrane. We hypothesize that Oatps mediate the first and rate-limiting step in the transport of structurally diverse amphipathic OAs across the BCSFB and that the expression and activity of Oatps and Mrps at the BCSFB are regulated by aging. The goals of this application are to determine the functional characteristics of the BCSFB amphipathic OA transport system, define the role of Oatp1a transporters in BCSFB transport, and explore age-dependent changes in transporter expression and function at the BCSFB. The proposed studies will build a functional and mechanistic framework for a major xenobiotic clearance pathway at the BCSFB and pave the way for future studies to investigate the impact of BCSFB transporters and aging on CNS drug disposition, pharmacokinetics and pharmacodynamics.
Personnel
Wang, Joanne, Principal Investigator, Professor, PHARMACEUTICS • SUN, AUSTIN, Other, Research Assistant (E S UAW ASE), PHARMACEUTICS • Camp, Alyssa L, Administrative Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
SA1112602 - SAA Bansal FHCC Ramsey.
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 06/03/2022
Sponsor: Fred Hutchinson Cancer Center (FHCC) Amount: $6180
Abstract
The goal of the proposed work is to provide statistical expertise on Dr. Ramsey's funded project, supporting the accomplishment of workscope for this project at FHCRC
Personnel
Bansal, Aasthaa, Principal Investigator, Research Assistant 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Stakeholder Convening Support PCORI Sickle Cell.
BASU, ANIRBAN , Department Of Pharmacy
Award Date: 05/31/2022
Sponsor: Sick Cells Amount: $14000
Abstract
Sick Cells proposes to convene a group of stakeholders including patients, caregivers, researchers, clinicians, health economists, payers, purchasers/employers, and community-based organizations to drive consensus on important inputs to measure value in SCD. Through this convening, stakeholders will foster new partnerships and facilitate discussion around development of priority elements, methods, and engagement plans for future patient-centered outcomes research (PCOR), comparative effectiveness research (CER), and value assessments.
Personnel
Basu, Anirban, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Devine, Emily E., Key Personnel, 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Value-based Formulary-Essentials: Testing and Expanding on Value in Prescription Drug Benefit Design.
SULLIVAN, SEAN , Department Of Pharmacy
Award Date: 05/26/2022
Sponsor: Kaiser Permanente Washington Health Research Institute Amount: $1060
Abstract
Dr. Sullivan will provide expertise in effective engagement and dissemination of study results to payersand purchasers, and will be available to meet 1-2 times per month to discuss study progress.
Personnel
Sullivan, Sean, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Chen, Yilin, 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Predicting Fetal Drug Exposure with a Maternal-Fetal PBPK Model.
Unadkat, Jashvant D , Pharmaceutics
Award Date: 05/06/2022
Sponsor: Bill and Melinda Gates Foundation Amount: $530570
Abstract
Pregnant women are administered medications for various preexisting or pregnancy-induced conditions. These medications may present risks of toxicity or lack of efficacy to fetus at various gestational ages. Therefore, it is important to understand drug exposure and pharmacological effects on the fetus upon maternal drug administration. However, for ethical reasons, drug exposure and effects in the fetus are not easily studied in clinic. Physiologically-based pharmacokinetic (PBPK) models incorporate physiological and drug-related information into a virtual trial design to predict drug exposure in silico. They present a unique and valuable tool for comprehensive understanding of interactions between drug molecule and human physiology. Depending on the questions to be addressed and the confidence in a maternal-fetal PBPK (m-f-PBPK) model structure, simulations can be useful to support dose selection in pregnant women to ensure safety and efficacy of drugs transferred to the fetus. A prototype m-f-PBPK model has been published by Zhang et al, 2017[1,2] by the Principal Investigator at the University of Washington. The model successfully predicted fetal exposure to drugs passively diffused through the placenta and those effluxed [3] by placental P-glycoprotein (P-gp). This model incorporated the effect of gestational age, and developmental changes of fetus. With continuing verification and addition of parameters relevant to feto-placental transport and metabolism, the model can be expanded (e.g. BCRP or BCRP and P-gp efflux) to make predictions for more medications. Such predictions are important to support safe and effective use of therapeutic drugs in pregnant women.
Personnel
Unadkat, Jashvant D, Principal Investigator, Professor, PHARMACEUTICS • Kirkpatrick, Leila, Administrative Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, Budget Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS
Health Outcomes Research Fellowship Jiang.
VEENSTRA, DAVID , Department Of Pharmacy
Award Date: 05/06/2022
Sponsor: PhRMA Foundation Amount: $50000
Abstract
A promise of precision medicine is to identify patients at risk of disease so that preventative treatment and screening can be initiated. Polygenic risk scores (PRSs), an exciting new development in the field, use machine learning (ML) models and information from variants in common genes to predict risk of diseases such as cancer and cardiovascular disease. The clinical and economic value of PRS, however, are unclear. ObjectiveIn this study, I propose to improve PRS risk prediction using colorectal cancer (CRC) as a case study and examine clinical and economic value of CRC PRS and its role in health equity. MethodsIn Aim 1, I will improve CRC PRS by incorporating information from other disease PRSs, using ML techniques. In Aim 2, I will use a microsimulation model to assess clinical and economic value of PRS in guiding CRC prevention and early diagnosis. Specifically, I will identify the optimal threshold for PRS risk stratification across racial/ethnic groups. ImplicationsThe results will provide a framework for improving and assessing PRS for disease risk prediction and initiation of preventative treatments and screening using health economics tools.
Personnel
Veenstra, David, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • JIANG, SHANGQING, Fellow, Research Assistant (E S UAW ASE), DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Hayes, Lori T, eGC1 Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICINE
A Systems Pharmacology approach to predict the effects of pregnancy and infectious diseases on transporter-mediated drug disposition.
UNADKAT, JASHVANT D , Pharmaceutics
Award Date: 05/04/2022
Sponsor: National Institutes of Health (NIH) Amount: $435877
Abstract
Pregnancy and inflammation (due to infectious diseases) are each known to alter drug pharmacokinetics (PK) by changing the expression and activity of transporters and/or drug-metabolizing enzymes (e.g. CYPs). Quantifying changes in drug PK caused by pregnancy and/or cytokines (elevated during inflammation) is important for rational design of dosing regimens of drugs for pregnant women with infectious diseases. While changes in the PK of CYP-cleared drugs by pregnancy and cytokines have been well-delineated using CYP probe drugs, such data are sorely missing for transporters. However, obtaining data of changes in drug PK by pregnancy and/or pro-inflammatory infectious diseases for every possible transported drug administered to pregnant women (with or without infection) is logistically impossible. Therefore, alternative approaches that can generalize across drugs, transporters and pro-inflammatory infectious diseases are urgently needed. These approaches should accurately predict the alteration in in vivo activity of transporters by pregnancy and pro-inflammatory cytokines. In this proposal, we propose a systems pharmacology approach to predict the effects of pregnancy and/or pro-inflammatory infectious diseases on transporter-mediated drug PK. Our hypothesis is that the magnitude of change in drug PK by pregnancy and/or cytokines can be predicted through clinical PK studies using probe drugs and in vitro experimental data as well as Physiologically Based Pharmacokinetic (PBPK) modeling and simulation (M&S). While probe drugs can yield clinically significant and valuable data, transporter probe drugs, unlike CYP probe drugs, have the limitations that they are not selective. Therefore, to overcomethis limitation, we propose a two-pronged approach which utilizes both primary human cells (e.g. hepatocytes, renal epithelial cells, intestinal enterocytes) and transfected cells expressing individual transporters of interest. Using quantitative targeted proteomics, the human cells will allow us to determine the effect of pregnancy hormones or cytokines, on the expression of transporters in these cells. The transportertransfected cell studies will allow us to determine the intrinsic transport clearance of a drug by a single transporter per pmol of a transporter. Combined, these data will allow us to predict, through PBPK M&S,transporter-mediated clearance of drugs in pregnant women with and without infection. These studies will address a critical gap in our understanding of the effects of pregnancy and/or pro-inflammatory infectious diseases on transporter-mediated drug disposition. Since our approach can be applied to other drugs and other inflammatory diseases, its significance goes well beyond the drugs and inflammatory diseases investigated here. We would like this application to be considered under the NIH-FAPESP initiative (NOT-TW-16-001). Under this initiative, the clinical PK studies will be conducted in pregnant women with infectiousdiseases in Brazil, and the clinical PK data obtained will be used to verify our PBPK model predictions.
Personnel
Unadkat, Jashvant D, Principal Investigator, Milo Gibaldi Endowed Professorship In Pharmaceutic, PHARMACEUTICS • Mao, Qingcheng, Multiple PI, Associate Professor, PHARMACEUTICS • Deprey, Teresa M, Administrative Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Deprey, Teresa M, Budget Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Deprey, Teresa M, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS
Incorporating Equity into Healthcare Decision Making Around New Technologies.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 05/04/2022
Sponsor: PhRMA Foundation Amount: $50000
Abstract
There is an increasing demand to incorporate equity into healthcare decisions around new technologies. The overall goal of this project is to generate evidence that can support the incorporation of equity into these decisions. First, we will use quasi-experimental designs to examine the extent to which our society has been currently trading off health and financial equity for overall health improvement at the introduction of new oncologic drugs. We will examine how this tradeoff varies with drug prices. Results will provide the motivation and equity inputs for value assessment and drug pricing discussions. Second, we will simulate the health and health disparity implications of adopting “race-neutral” vs “race-conscious” machine learning algorithms to support oncological treatment decisions. Results of this research will illuminate how to include fairness considerations into the development and evaluation of existing and future algorithms to guide equitable treatment decisions.
Personnel
Carlson, Joshua J., Principal Investigator, Associate Professor, DEPARTMENT OF PHARMACY • Khor, Sara, Fellow, Research Assistant (E S UAW ASE), DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Hayes, Lori T, eGC1 Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICINE
Drug Action, Metabolism and Kinetics Training Grant.
ATKINS, WILLIAM M. , Medicinal Chemistry
Award Date: 05/03/2022
Sponsor: National Institute of General Medical Sciences (NIGMS) Amount: $549075
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 • Meichle, Rebecca, Mentor, Adjunct Research Professor, PHARMACOLOGY • Sancak, Yasemin S., Mentor, Assistant Professor, PHARMACOLOGY • Shechner, David Michael, Mentor, Assistant Professor WOT, PHARMACOLOGY • Yadav, Smita, Mentor, Assistant Professor, PHARMACOLOGY • Bhardwaj, Gaurav, Mentor, Assistant Professor, MEDICINAL CHEMISTRY • Bajjalieh, Sandra M., Mentor, Professor, PHARMACOLOGY • Catterall, William A, Mentor, Chair, PHARMACOLOGY • Chavkin, Charles, Mentor, 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 • 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 • 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 • Nath, Abhinav, Mentor, Assistant Professor, MEDICINAL CHEMISTRY • Ong, Shao-En, Mentor, Assistant Professor, PHARMACOLOGY
Dynamics and Interactions of Cytochrome P450 19A1 .
Atkins, William M. , Medicinal Chemistry
Award Date: 04/29/2022
Sponsor: Florida International University Amount: $84726
Abstract
This project aims to understand the enzyme CYP19A which is responsible for steroid biosynthesis and has been established as a drug target for Breast Cancer. We aim to characterize the protein dynamics to understand how CYP1(A interacts with drugs and substrates.
Personnel
Atkins, William M., Principal Investigator, Professor, MEDICINAL CHEMISTRY • Kanov, Jeanine M., Administrative Contact, ADMINISTRATOR, Department of Medicinal Chemistry, MEDICINAL CHEMISTRY • Lidzbarski, Erik August Lee, Budget Contact, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY • Lidzbarski, Erik August Lee, eGC1 Preparer, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY • Lidzbarski, Erik August Lee, Advance Preparer, BUDGET/FISCAL ANALYST, MedChem - Admin, MEDICINAL CHEMISTRY
NextGen Targeted and Long-acting Combination ART for Children with HIV.
HO, RODNEY J.Y. , Pharmaceutics
Award Date: 04/22/2022
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) Amount: $1260148
Abstract
The Targeted, Long-acting and Combination Anti-Retroviral Therapeutic (TLC-ART) Program has developed a scalable, drug-combination nano-platform technology called DcNP that enables the stabilizing of insoluble and soluble HIV drugs together in an injectable suspension intended for children. The proposed transition plan is intended to select a lead and back up drug-combination candidate to support clinical development of a long-acting HIV treatment product for children. In the past 1.5 year, the team has made significant progress that we believe met or exceed the milestones laid out in the original award agreement. This transitional review package is assembled for a formal review and request for proceeding the proposed R33 phase award.
Personnel
Ho, Rodney J.Y., Principal Investigator, Professor, PHARMACEUTICS • Jonsson, Christine Anne, Other, MANAGER OF PROGRAM OPERATIONS, Department of Medic, DEPARTMENT OF MEDICINE • Collier, Ann C, Co-Investigator, Professor without Tenure, DEPARTMENT OF MEDICINE • Beima-Sofie, Kristin M, Co-Investigator, Acting Assistant Professor, GLOBAL HEALTH • Jonsson, Christine Anne, Administrative Contact, MANAGER OF PROGRAM OPERATIONS, Department of Medic, DEPARTMENT OF MEDICINE • Jonsson, Christine Anne, Budget Contact, MANAGER OF PROGRAM OPERATIONS, Department of Medic, DEPARTMENT OF MEDICINE • Fukuda, Yuichi, eGC1 Preparer, Program Operations Specialist (E S 7), DEPARTMENT OF MEDICINE • Fukuda, Yuichi, Advance Preparer, Program Operations Specialist (E S 7), DEPARTMENT OF MEDICINE
Rational Integration of Polygenic Risk Scores (RIPS).
Veenstra, David , Department Of Pharmacy
Award Date: 04/22/2022
Sponsor: Vanderbilt University Medical Center Amount: $263440
Abstract
There has been extraordinary growth in the past years of new techniques to predict common, complex disease based on polygenic risk scores (PRS). Without an understanding grounded in evidence, it is unlikely that clinical sequencing using PRS will propagate from highly specialized applications and environments to become adopted more broadly and provide greater benefit to the US population. Critical challenges include: 1) identification of risk thresholds for return of results that optimize patient outcomes and provide cost-effective care, 2) uncertainty in generalizability of PRS performance across diverse populations and subsequent impact on patient outcomes, and 3) prioritization of future research to improve outcomes in diverse populations. We propose to address these challenges using decision analytic modeling and by building on our extensive work in this area to create a novel framework capable of assessing PRSs in the context of monogenic and clinical risks. Our Rational Integration of SEquencing (RISE) consortium has created clinical-economic models to project lifetime clinical impact and cost-effectiveness for population-level genomic screening with return of monogenic disease risks associated with three CDC Tier 1 conditions: hereditary breast and ovarian cancer, Lynch syndrome, and familial hyperlipidemia. We have found population genomic screening offers significant promise, but clinical benefit-harm tradeoffs must be carefully assessed and screening for multiple conditions will be needed to achieve cost effectiveness. As part of this proposal, titled Rational Integration of Polygenic Risk Scores (RIPS), will develop and execute a framework for assessing the clinical outcomes and economic value of comprehensive genomic screening using PRS in modeled real-world settings and applied to large and diverse populations. The Aims of the proposal include 1) to evaluate published and real-world evidence on the how returning genetic information impacts provider and patient behavior 2) to understand the impact of PRS performance and return thresholds on clinical benefit and cost-effectiveness for coronary artery disease (CAD), breast cancer, and colorectal cancer, and 3) To develop principles and research priorities for the equitable development and implementation of PRS across heterogenous populations.
Personnel
Veenstra, David, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Guzauskas, Greg, Key Personnel, Research Scientist/Engineer 4 (E S 9), 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Role of epithelial cell intrinsic vitamin A metabolism in regulating immune homeostasis in the gut.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 04/08/2022
Sponsor: Brown University Amount: $3927
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 • Chau, Alvin, Administrative Contact, BUDGET/FISCAL ANALYST LEAD, PCEUT - ADMIN, PHARMACEUTICS • Ava, Afshan, Budget Contact, Administrator (E S 10), SCHOOL OF SOCIAL WORK • Ava, Afshan, eGC1 Preparer, Administrator (E S 10), SCHOOL OF SOCIAL WORK • Royall, Frederick, Advance Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Sudden cardiac arrest and circulating hydrogen sulfide.
TOTAH, RHEEM A , Medicinal Chemistry
Award Date: 04/07/2022
Sponsor: National Institutes of Health (NIH) Amount: $642990
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
SA1105622 - SAA Bansal FHCC Ramsey.
BANSAL, AASTHAA , Department Of Pharmacy
Award Date: 03/31/2022
Sponsor: Fred Hutchinson Cancer Center (FHCC) Amount: $477
Abstract
The goal of the proposed work is to provide statistical expertise on Dr. Ramsey's funded project, supporting the accomplishment of workscope for this project at FHCRC
Personnel
Bansal, Aasthaa, Principal Investigator, Research Assistant 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Home vs. Clinic Collection of Human Milk in Evaluating the Pharmacokinetics of Four Medications.
HEBERT, MARY F , Department Of Pharmacy
Award Date: 03/02/2022
Sponsor: University of California, San Diego (UCSD) Amount: $1495
Abstract
This project proposes a systematic approach to validate methods for home collection of breastmilk and blood samples. This will lead to a marked expansion of eligible lactating women for research to build a critical mass of data to make strong clinical recommendations regarding nursing infant exposure and safety of drug exposure via breastmilk
Personnel
Hebert, Mary F, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Administrative Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Kimura, Maya, eGC1 Preparer, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY
Value-based Formulary-Essentials: Testing and Expanding on Value in Prescription Drug Benefit Design.
SULLIVAN, SEAN , Department Of Pharmacy
Award Date: 02/24/2022
Sponsor: Kaiser Permanente Washington Health Research Institute Amount: $6240
Abstract
Dr. Sullivan will provide expertise in effective engagement and dissemination of study results to payersand purchasers, and will be available to meet 1-2 times per month to discuss study progress.
Personnel
Sullivan, Sean, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Chen, Yilin, 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Long-term effects of today's medical care access policies on the future burden of Alzheimer's Disease and related dementias.
BARTHOLD, DOUGLAS G. , Department Of Pharmacy
Award Date: 02/18/2022
Sponsor: National Institutes of Health (NIH) Amount: $122040
Abstract
The management of cardiovascular and metabolic health, including type 2 diabetes mellitus (T2DM), is an important part of healthy aging and affects risk of Alzheimer’s disease and related dementias (ADRD). The proposed research aims to examine how the effects of today’s health insurance benefit design on management of T2DM can lead to long-term consequences on the incidence and burden of ADRD. This will be accomplished with an innovative simulation model, that connects existing models of T2DM progression and aging, to build understanding of the complicated interplay between health policies, healthy aging, and ADRD.
Personnel
Barthold, Douglas G., Principal Investigator, Research Assistant Professor, DEPARTMENT OF PHARMACY • Grabowski, Thomas J, Other, Professor, RADIOLOGY • Basu, Anirban, Mentor, Professor, DEPARTMENT OF PHARMACY • Odegard, Peggy Soule, Mentor, Professor, DEPARTMENT OF PHARMACY • Liu, Shan, Mentor, Associate Professor, INDUSTRIAL&SYSTEMS ENG • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Beat MS.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 02/16/2022
Sponsor: Benaroya Research Institute at Virginia Mason Amount: $43310
Abstract
Dr. Carlson, 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 • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Hayes, Lori T, eGC1 Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICINE
Adult Changes in Thought (ACT) Research Program.
CRANE, PAUL K , Department Of Pharmacy
Award Date: 02/16/2022
Sponsor: Kaiser Permanente Washington Health Research Institute Amount: $104499
Abstract
The Adult Changes in Thought (ACT) study is a prospective longitudinal observational study of more than 5,500 older adults enrolled from Kaiser Permanente Washington, an integrated healthcare delivery system with extensive clinical data. The ACT U19 Program’s primary goals are to continue and enhance ACT’s leadership as a living, learning laboratory for aging research; to continue and enhance ACT’s leadership in dementia and Alzheimer’s research; and to continue and enhance ACT’s leadership in providing exceptional resources to the research community. The rationale for this study is that prospective cohort studies of well-characterized individuals are critical for furthering scientific understanding the health of older adults. The ACT study is in a unique position to serve these roles since it has amassed some 57,000 person-years of follow-up to date, has identified more than 1,200 incident dementia cases and more than 1,000 incident Alzheimer’s cases, has performed more than 800 autopsies, and has provided critical data and/or specimens to enable the research careers of dozens of investigators to date. Our overall objectives are to continue and enhance our leadership roles by: (1) increasing our sample size from 2,000 to 3,000 people alive and at risk of dementia outcomes, while enhancing diversity by extending our catchment area and oversampling ethnic minorities; (2) further extending the reach of our rapid autopsy protocol and performing slide scanning, postmortem imaging, and artificial intelligence-aided and biochemical continuous assays of brain tissues, while preserving meninges to support induced pluripotent stem cell-driven research; (3) integrating a life course epidemiology perspective on our data, further enhancing our medical records data abstraction and introducing geographical analysis approaches for the ACT cohort; (4) collecting MRI and tau PET scans on a subset of ACT participants to augment clinical and research-derived MRI scans available from the ACT cohort, and analyzing those data with state of the art methods including artificial intelligence-aided approaches; (5) compiling ACT genomic and other systematic molecular data from ACT participants in a single location and augmenting their value by incorporating extensive external genome-wide annotation data; (6) providing exceptional biostatistical support and supporting extensive use of ACT study data by external investigators; (7) supporting four scientific Projects addressing critical issues in older adults and in dementia and Alzheimer’s disease. With this application, we are requesting funds to continue and enhance the longitudinal clinical and cognitive assessment of the cohort, to increase the cohort size and diversity, to enhance our neuropathological workup of brain tissues from consenting decedents, to collect tau PET and MRI scans on selected cohort members, and to support the work of four Projects that address (1) sleep and movement ; (2) cognitively-defined Alzheimer’s subgroups; (3) brain effects of commonly used medications in older adults using epidemiology and induced pluripotent stem cell approaches; and (4) identifying prodromal Alzheimer’s disease with tests of central auditory processing and lexical semantic retrieval. These activities will enable ACT to further enhance its extensive data sharing with investigators locally, across the country, and around the world.
Personnel
Crane, Paul K, Principal Investigator, Associate Professor, DEPARTMENT OF MEDICINE • Chin, David G., Other, BUDGET/FISCAL ANALYST LEAD, Department of Medicine, DEPARTMENT OF MEDICINE • Choi, Seo-Eun, Other, Research Scientist/Engineer 4 (E S 9), DEPARTMENT OF MEDICINE • Panks, Christopher, Other, RESEARCH SCIENTIST/ENGINEER 1, Neurological Surger, NEUROLOGICAL SURGERY • Peterson, Daniel, Other, RESEARCH SCIENTIST/ENGINEER 1, Radiology: Integrat, RADIOLOGY • Zalewski, Kody, Other, Research Scientist/Engineer 1 (NE S 6), NEUROLOGICAL SURGERY • Boorkman, Patti A., Other, Psychometrist 2, DEPARTMENT OF MEDICINE • Mohamath, Duryah, Other, Computer Support Analyst 1, DEPARTMENT OF MEDICINE • Fulcher, VIRGINIA, Other, Data Control Technician 1, DEPARTMENT OF MEDICINE
Impact of anticholinergic and dopamine receptor blocking drug exposure on Parkinson Disease trajectory and outcomes.
GRAY, SHELLY L. , Department Of Pharmacy
Award Date: 02/16/2022
Sponsor: University of Pennsylvania Amount: $34317
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 • Ahmed, Saveena, Administrative Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Contact, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
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: 02/08/2022
Sponsor: University of Utah Amount: $69083.5
Abstract
The systemic kainic acid (KA)-induced status epilepticus (SE) model in rats is an etiologically-relevant animal model of epileptogenesis. All of the clinical characteristics observed in human patients with temporal lobe epilepsy (TLE) are also observed in the rat systemic KA model of SE and TLE. Moreover, the systemic low-dose KA paradigm is ideally suited for preclinical drug screening studies to evaluate the long-term process of epileptogenesis. As a first attempt to identify novel and potentially efficacious antiepileptogenic agents, it is necessary to define whether administration of the investigational compound during the SE insult or immediately after (e.g. during the latent period) can first modify presentation and severity of spontaneous recurrent seizures, as well as attendant comorbidities, in the rat KA-SE model of epileptogenesis. The goal of the proposed studies is to determine whether administration of promising investigational anticonvulsant compounds can also modify or attenuate the presentation of spontaneous recurrent seizures days to weeks after SE, as well as modify the SE-induced behavioral deficits associated with TLE.
Personnel
White, Harold Steve, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Haliski, Melissa, Key Personnel, Research Scientist/engineer-senior, DEPARTMENT OF PHARMACY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Ahmed, Saveena, Budget Contact, Program Operations Analyst (E S 7), DEPARTMENT OF PHARMACY • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • , Dept Of Pharmacy, Budget Preparer, , • Luetjen, Karen H., Advance Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, Pharm - A, DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
PQM UW#3 under USAID Cooperative Agreement No. 7200AA19CA00025 Promoting the Quality of Medicines Plus (PQM+) with USP.
STERGACHIS, ANDREAS S , Department Of Pharmacy
Award Date: 12/29/2021
Sponsor: U.S. Pharmacopeial Convention (USP) Amount: $50000
Abstract
The Promoting the Quality of Medicines Plus (PQM+) program is a five-year (September 27, 2019 - September 26, 2024) U.S. Agency for International Development (USAID)-funded cooperative agreement to sustainably strengthen medical product quality assurance systems in low- and middle-income countries (LMICs). PQM+ provides technical assistance to build the in-country capacity of medical products regulatory authorities’ quality assurance systems in assisted countries. PQM+ also provides technical support to manufacturers of quality-assured priority medical products for malaria, tuberculosis (TB), neglected tropical diseases (NTD), COVID-19, other infectious diseases, family planning and reproductive health, and maternal, newborn, and child health (MCH). To build on the progress made in PY2, in PY3, PQM+ will pilot the model to estimate the health and economic burden of SF medicines for oxytocin injection (used to prevent post-partum hemorrhage in pregnant women) in Kenya and for an anti-tuberculosis medicine in Pakistan. These two countries were selected based on predefined criteria, including PQM+ presence; sizable program portfolio; long track records of PQM/PQM+ support; strong working relationships with government counterparts; PQM+ Chiefs of Party and USAID Mission Activity Managers’ interest and concurrence; availability of and access to data sources on SF oxytocin and first-line anti-tuberculosis medicines, aggregated health and disease incidence/prevalence in both the public and private sector, medication costs, pharmaceutical production and distribution, health spending of the government and household, etc.This is Task Order 3. USP leads a consortium of partners that complements our core strengths, technical knowledge, and geographic reach to achieve the goal of the PQM+ program. The University of Washington (UW) is a technical resource partner for the program. UW’s School of Pharmacy Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute’s Global Medicines Program works to improve the use, safety, quality, risk-benefit profile, cost-effectiveness, and affordability of medicines in LMICs. The UW Program conducts field-based research, pre-service and in-service education and training, and capacity-strengthening technical assistance in a variety of LMICs.
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 • Hayes, Lori T, eGC1 Preparer, Program Operations Specialist (E S 8), REHABILITATION MEDICINE
Population-based Interventions to Improve Behavioral Health in a Tribal Healthcare System.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 12/01/2021
Sponsor: Southcentral Foundation Amount: $6010
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 • Deprey, Teresa M, Administrative Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Royall, Frederick, Budget Contact, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, eGC1 Preparer, Grants And Contracts Manager/specialist, PHARMACEUTICS • Royall, Frederick, Advance Preparer, GRANTS AND CONTRACTS MANAGER/SPECIALIST, PCEUT - A, PHARMACEUTICS
Utilizing Private Pharmacy Capacity and Systems for COVID-19 Vaccine Delivery and Future Life-Course Vaccines.
Stergachis, Andreas S , Department Of Pharmacy
Award Date: 11/19/2021
Sponsor: PATH Amount: $91662
Abstract
Under the oversight of Dr. Stergachis, University of Washington study personnel will contribute to start-up activities for the PATH/Ghana Pharmacy T.R.U.S.T. Initiative, aiming to train pharmacists in Ghana to safely deliver the COVID-19 vaccine. The UW study team will engage in collaborative efforts with PATH, Ghana College of Pharmacy, and Ghana Ministry of Health to begin development of a pharmacist vaccination train-the-trainer program. During the first 3 months, study personnel will focus on project start-up activities, including project lifecycle planning and begin the development of curriculum modules.
Personnel
Stergachis, Andreas S, Principal Investigator, Professor, DEPARTMENT OF PHARMACY • Sullivan, Catrena J, Other, Clinical Assistant Professor - Non Salaried, RUBENSTEIN PHARMACY • Downing, Donald F, Co-Investigator, Clinical Professor - Salaried, DEPARTMENT OF PHARMACY • Odegard, Peggy Soule, Co-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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Engagement of University of Washington to undertake data analysis for point prevalence survey and antimicrobial stewardship interventions..
Stergachis, Andreas S , Department Of Pharmacy
Award Date: 11/02/2021
Sponsor: Management Sciences for Health (MSH) Amount: $40000
Abstract
The USAID Medicines, Technologies and Pharmaceutical Services (MTaPS) program, implemented by MSH, is supporting Uganda to develop capacity to combat antimicrobial resistance (AMR) through implementing activities that aim to improve Uganda’s JEE score towards the GHSA 2024 target of ‘demonstrated’ capacity (level 4). MTaPS’ technical assistance is implemented across 3 AMR containment result areas, Infection Prevention and Control (IPC), Antimicrobial stewardship (AMS) and effective multisectoralcoordination (MSC).
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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Virtual Pregnancy: Physiologically-based modeling in pregnancy.
ISOHERRANEN, NINA , Pharmaceutics
Award Date: 10/26/2021
Sponsor: Bill and Melinda Gates Foundation Amount: $222593
Abstract
The Bill & Melinda Gates Foundation (BMGF), in its efforts to improve global maternal and child health, seeks to accelerate drug development for pregnant and lactating women (PLW) in low- and middle-income countries Ultimately, the output of these efforts is envisioned to be a Globally-Accepted Virtual Pregnancy Model that will serve as an in-silico resource to accelerate model-informed drug development (MIDD). At present The availability of maternal-fetal pharmacokinetic information of drugs used to treat infectious diseases that are relevant to pregnant women in west Africa is extremely limited. In addition, limited information is available on population factors that may need to be refined for the west African population to achieve efficacious dosing regimens. This project aims to address these gaps in our current knowledge and in the treatment of pregnant women via employing a Physiologically-Based Pharmacokinetic (PBPK) modeling strategy to predict how disposition of drugs used specifically to treat infectious diseases in west African pregnant women changes during pregnancy. Our long-term goal is to develop PBPK models that incorporate disease related effects on maternal physiology, population parameters relevant to the west African population and pregnancy parameters that enable simulation of maternal-fetal disposition across gestational timeline. In this proposal we will focus on treatment of two infectious diseases, lassa fever and tuberculosis that specifically affect pregnant women in Nigeria to 1) develop pregnancy-PBPK models that provide simulations that can be directly translated to improved care of pregnant women in west Africa and tested in clinical populations
Personnel
Isoherranen, Nina, Principal Investigator, Professor, PHARMACEUTICS • Amaeze, Ogochukwu Ukamaka, Key Personnel, Postdoctoral Scholar, PHARMACEUTICS • Kirkpatrick, Leila, Administrative Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, Budget Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Kirkpatrick, Leila, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS
Institute for Clinical and Economic Review 2022-2023.
CARLSON, JOSHUA J. , Department Of Pharmacy
Award Date: 10/25/2021
Sponsor: Institute for Clinical and Economic Review Amount: $333500
Abstract
In this project, the CHOICE team will develop cost-effectiveness models to estimate the cost per outcomes achieved as well per patient cost estimates for ICER generated review topics. We will participate in the project meetings and calls, the development of the health technology assessment reports and the public presentations of the findings. We will participate in 7 reviews over the course of the project.
Personnel
Carlson, Joshua J., Principal Investigator, Associate Professor, DEPARTMENT OF PHARMACY • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Budget Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Neurocrine Fellowship 2022-2024.
HANSEN, RYAN , Department Of Pharmacy
Award Date: 10/25/2021
Sponsor: Neurocrine Biosciences, Inc. Amount: $393017
Abstract
Neurocrone Inc. supports a two-year fellowship program in Health Economics and Outcomes Research (HEOR) through the University and its Department of Pharmacy.
Personnel
Hansen, Ryan, Principal Investigator, Associate Professor, DEPARTMENT OF PHARMACY • Sullivan, Sean, Multiple PI, 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 • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY
Natural Product-Drug Interaction Research: The Roadmap to Best Practices.
THUMMEL, KENNETH E. , Pharmaceutics
Award Date: 10/14/2021
Sponsor: Washington State University (WSU) Amount: $461738
Abstract
Administrative Core The 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) identifying a priority list of NPs that will be investigated for drug interaction liabilities, 2) designing appropriate in vitro and clinical interaction studies involving the selected NPs, 3) supporting the interaction projects by sourcing and ensuring quality of the NP study materials and by coordinating analysis of the pharmacokinetic samples generated from the interaction projects, and 4) disseminating the data generated from the interaction projects via a robust data repository and public-facing portal.The Administrative Core component of this subcontract supports the effort of Dr. Kenneth Thummel (Co-I). Dr. As a member of the Administrative Core and Steering Committee, Dr. Thummel will provide advice and counsel for all elements of the programmatic function of the Administrative Core, including execution of the Interaction Projects, development of new recommended approaches (RAs) and the dissemination of NaPDI research findings and evaluation of its impact on the research community.Pharmacology Core For the 5-year period of the parent grant, the Pharmacology Core has the principal responsibility of designing and implementing the Interaction Projects. The process begins with the selection of natural products (NPs) for investigation by the NaPDI team. This occurs in concert with input from the Steering Committee (representing leadership of all Cores and the NCCIH grant program officer). The list of NPs proposed in this grant application (kratom, hemp, goldenseal/echinacea, and black pepper) is the result of such interactions. The NP priority list will be updated regularly throughout the course of the grant, as described in our Research Strategy. NP selection is the product of an extensive literature review and, for kratom and hemp, carefully orchestrated preclinical studies that led to a definitive assessment of their risk or safety and the need for further investigation. Additional pre-clinical interaction studies of selected NPs will be performed by the Pharmacology Core team, as needed. Results will be evaluated using rigorous, predefined decision trees as guides, for determination of the need for a clinical NP-drug interaction study, and implemented, as described in the Research Strategy.The Pharmacology Core component of this UW subcontract supports the efforts of Dr. Allan Rettie (Co-I) and Dr. Jashvant Unadkat (Co-I), two preeminent translational pharmacologists, and their lab personnel. The two Co-I will work with the Pl of the parent grant, Dr. Mary Paine, in reassessing current priority natural products: kratom, hemp, combined goldenseal/echinacea and black pepper, and in periodically evaluating new, emerging NPs for prioritization. The UW portion of the Pharmacology Core will conduct all the necessary preclinical studies for identifying potential drug interactions with hemp and the combined goldenseal/echinacea product and associated constituents. At present, the preclinical studies will largely consist of validated in vitro screening assays for known drug metabolizing enzymes; possible interactions with drug transporters will be sub-contracted to Solvo. Bench support will be provided by a qualified postdoctoral fellow in Dr. Unadkat’s lab, Dr. Sumit Bansal, and a senior staff scientist in Dr. Rettie’s lab, Dr. Matt McDonald. Dr. Unadkat will also oversee the development of PBPK models for cannabidiol (from hemp) and goldenseal/echinacea – probe drug interactions.Analytical Core Under 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) isolating and supplying the bioactive extracts of selected natural products for preclinical studies on drug interaction potentials, and 3) supporting the analysis of samples generated from the clinical human subject studies under the Interaction Projects. The Analytical Core component of this UW subcontract will focus on the third charge, mainly to provide the critical analytical support for the clinical studies on standardized hemp and goldenseal/echinacea extracts 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 drug and/or metabolites of the drug probes used in the enzyme or transporter screens and key constituents present in the natural product extracts (i.e., the perpetrators). 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 of kratom and black pepper, under the Interaction Projects. As currently proposed, these analyses are to be 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 generated from pre-clinical studies by investigators in the Pharmacology Core (i.e, labs of Drs. Unadkat and Rettie).
Personnel
Thummel, Kenneth E., Principal Investigator, Professor, PHARMACEUTICS • Brauchla, Calder C, Other, Research Scientist/Engineer 1 (E S 6), PHARMACEUTICS • Bansal, Sumit, Other, Postdoctoral Scholar (E S UAW Postdoc), PHARMACEUTICS • McDonald, Matthew G., Other, RESEARCH SCIENTIST/ENGINEER 3, MedChem - Rettie La, MEDICINAL CHEMISTRY • Unadkat, Jashvant D, Co-Investigator, Professor, PHARMACEUTICS • Rettie, Allan E., Co-Investigator, Professor, MEDICINAL CHEMISTRY • Kimura, Maya, Administrative Contact, ADMINISTRATOR, Department of Pharmacy, DEPARTMENT OF PHARMACY • Kirkpatrick, Leila, Budget Contact, Grants And Contracts Manager/Specialist (E S 8), PHARMACEUTICS • Camp, Alyssa L, eGC1 Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Camp, Alyssa L, Advance Preparer, Grants And Contracts Manager/Specialist (E S 9), DEPARTMENT OF PHARMACY • Deprey, Teresa M, Advance Preparer, Administrator (E S 11), DEPARTMENT OF MEDICINE