Bhagwat Prasad

Assistant Professor

Department of Pharmaceutics, Pharmaceutics Faculty , UWPKDAP , UWRAPT

Telephone: (206) 221-2295

Email: bhagwat@uw.edu

Office Location: H268, Health Science Building

Website: Prasad lab

Education

  • Ph.D. and Master of Science in Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, India
  • Bachelor in Pharmaceutical Sciences, HNB Garhwal University, India

Research Interests

The overarching objective of our research is to investigate mechanisms of age-dependent variability in xeno- and endo-biotic disposition. Our current research projects involve the use of state-of-the-art LC-MS/MS quantitative proteomics and metabolomics to elucidate inter-individual differences in the abundances and activities of non-cytochrome P450 (non-CYP) drug metabolizing enzymes and transporters (DMET) in human tissues. We then integrate these data into physiologically-based pharmacokinetic (PBPK) models to predict variability in drug disposition. Such approaches are particularly important to predict drug disposition in special populations such as pediatrics where clinical studies are not often feasible. Currently, we have four specific projects undergoing in our laboratory.

  1. Development and validation of DMET quantitative proteomics methods: We apply robust LC-MS/MS proteomics approach to quantify DMET proteins in human and animal tissues, subcellular fractions and cells. We have developed a repository of LC-MS/MS methods for quantification of >280 human DMET proteins. We are also developing novel non-invasive methods for predicting drug disposition, e.g., by quantifying drug transporters in exosomes. These methods are being utilized to quantify effect of age, genotype and disease condition on expression of DMET proteins.
  2. PBPK prediction of ontogeny mediated hepatic and renal drug disposition: Our NICHD funded research utilizes in-house generated protein quantification data of hepatic DMET proteins to build PBPK models for prediction of age-dependent hepatic drug disposition. Such approaches are critical in determining first-in-children dose. We are also investigating age-dependent pharmacokinetics and pharmacodynamics of diuretics.
  3. Effect of UGT2B17 variability on drug and sex-steroid disposition: We are investigating the effect of age, gender and genetic polymorphism related variability of UGT2B17 on metabolism of typical UGT substrates including sex-steroids such as testosterone, dihydrotestosterone and estradiol.
  4. Integrated proteomics and metabolomics analysis of the steroidogenic pathway: We are also investigating age-dependent changes in steroidogenic pathway with respect to the role of hepatic and intestinal DMET proteins during human development. The quantitative proteomics and metabolomics assays developed in our laboratory are used to better elucidate mechanisms of fluctuations in levels of steroidal hormones.

 

Biography

I am a pharmacist by education with major research training in the field of pharmaceutical analysis. My recent research is focused on application of liquid chromatography-mass spectrometry (LC-MS) and quantitative proteomics to understand interindividual variability in drug disposition. Before joining as an assistant professor at UW Pharmaceutics, I worked with Prof. Jash Unadkat as a postdoc and a lead scientist of UW Research Affiliate Program on Transporters (UWRAPT). I obtained my MS in 2006 and Ph.D. in 2010 in Pharmaceutical Sciences from NIPER, Mohali, India. In my role as a PI or co-Inv. in various NIH and industry funded grants, I have been establishing and applying quantitative proteomic assays to quantify population variability in DMET proteins

Selected Publications

 

PubMed

  1. Bhatt DK, Gaedigk A, Pearce R, Leeder S, Prasad B, Age-dependent Protein Abundance of Cytosolic Alcohol and Aldehyde Dehydrogenases in Human Liver, Drug Metab and Dispos, 2017.
  2. Xu M, Bhatt DK, Yeung CK, Claw KG, Singh A, Gaedigk A, Pearce R, Gaedigk R, Nickerson D, Schuetz E, Rettie AE, Leeder SJ, Thummel KE, Prasad B, Genetic and Non-genetic Factors Associated with Protein Abundance of Flavin-containing Monooxygenase 3 in Human Liver, Accepted for publication in J Pharmacol Exp Ther, 2017.
  3. Bhatt DK and Prasad B, Critical issues and optimized practices in quantification of protein abundance level to determine inter-individual variability in DMET proteins by LC-MS/MS proteomics, Accepted for publication in Clin Pharmacol Ther, 2017(Review article).
  4. Boberg M, Vrana M, Mehrotra A, Pearce R, Gaedigk A, Leeder JS, Prasad B. Age dependent absolute abundance of hepatic microsomal carboxylesterases (CES1 and CES2) by LC-MS/MS proteomics: Application in prediction of in vivo pharmacokinetics of oseltamivir, Drug Metabolism and Disposition, 2016.
  5. Prasad B, Johnson K, Billington S, Lee CA, Chung GW, Brown CDA, Kelly E, Himmelfarb J, Unadkat JD. Abundance of drug transporters in the human kidney cortex as quantified by LC-MS/MS proteomics Drug Metabolism and Disposition, 2016 (dmd. 116.072066).
  6. Vrana M, Goodling A, Afkarian M, Prasad B, An optimized method for protein extraction from OCT-embedded human kidney tissue for protein quantification by LC-MS/MS proteomics” Drug Metab and Dispos,2016:44, 1692-1696.
  7. Prasad B.,Gaedigk A., Vrana N., Gaedigk R., Leeder J.S., Salphati L., Chu X., Xiao G., Hop C.E.C.A., Evers R., Gan L., Unadkat J.D.,Ontogeny of Hepatic Drug Transporters as Quantified by LC-MS/MS Proteomics, Clin Pharmacol Therap [Epub ahead of print], 2016.
  8. Prasad B, Garg A, Takwani H, Singh S. Metabolite identification by liquid chromatography-mass spectrometry. Trends in Analytical Chemistry. 2011;30:360-87.
  9. Prasad B, Evers R, Gupta A, Hop CE, Salphati L, Shukla S, et al. Interindividual Variability in Hepatic Oatps and P-Glycoprotein (ABCB1) Protein Expression: Quantification by LC-MS/MS and Influence of Genotype, Age and Sex. Drug Metab Dispos.2013 Oct 11.
  10. Prasad B, Lai Y, Lin Y, Unadkat JD. Interindividual variability in the hepatic expression of the human breast cancer resistance protein (BCRP/ABCG2): effect of age, sex, and genotype. J Pharm Sci.2013 Mar;102(3):787-93.
  11. Prasad B, Unadkat JD. Optimized Approaches for Quantification of Drug Transporters in Tissues and Cells by MRM Proteomics. AAPS J.2014 Jul;16(4):634-48.
  12. Prasad B, Singh S. In vitro reaction phenotyping studies on rifamycins to explain the auto-induction of rifabutin metabolism. Int J Tuberc Lung Dis. 2012 Feb;16(2):232-4.