Prasad Lab at ISSX Virtual Workshop: Current Status and Perspectives on Endogenous Biomarkers of Drug Transporters
February 2024
Prasad Lab members attended the International Society for the Study of Xenobiotics (ISSX) Virtual Workshop: Current Status and Perspectives on Endogenous Biomarkers of Drug Transporters in February 2024 and presented their research.
Lightning Talks by Graduate students:
- Anoud Ailabouni: “Identification of endogenous substrates of renal organic cation transporters as potential biomarkers by untargeted metabolomics analysis of cimetidine-treated rat blood and urine samples.“
- Aarzoo Thakur: “De Novo identification and validation of human endogenous biomarkers of renal organic anion transporters for predicting interindividual variability.“
Talk:
- Dr. Bhagwat Prasad: “Drug transporters in pediatrics: Ontogeny, variability, and clinical significance“
Anoud Ailabouni et al. published, ”Effect of cimetidine on metformin pharmacokinetics and endogenous metabolite levels in rats“ in Drug Metabolism and Disposition in February 2024.
February 2024
The discussion regarding the clinical significance of OCT versus MATE transporters in renal drug-drug interactions (DDI) is intriguing and requires additional mechanistic data. The metabolomics analysis of a preclinical study on cimetidine-metformin interaction revealed that cimetidine notably elevated plasma levels of metformin and concurrently reduced its renal clearance, alongside impacting several potential transporter biomarkers. Here we proposed a method to differentiate potential sensitive endogenous substrates of renal Oct1/2, hepatic Oct1, versus renal Mate transporters in rats. The suggested biomarkers in this research could serve to predict the DDI potential during preclinical investigations and contribute to a deeper understanding of the physiological roles of these transporters.
Deepak Ahire et al. published, ”Promiscuity and Quantitative Contribution of UGT2B17 in Drug and Steroid Metabolism Determined by Experimental and Computational Approaches“ in Journal of Chemical Information and Modeling in January 2024.
January 2024
In this study, we demonstrated, i) a structure-based pharmacophore model for UGT2B17 substrates and validated it using the in vitro experimental data, ii) estimated tissue-specific fraction metabolized (fm) of UGT2B17 substrates, and iii) identified inhibitors of UGT2B17 from the pool of selected compounds. Overall, this study demonstrated that UGT2B17 is a promiscuous enzyme that can facilitate glucuronidation of diverse functional groups.
Sheena Sharma et al. published, ”Analysis of the interplay of physiological response to food intake and drug properties in food-drug interactions“ in Drug Metabolism and Pharmacokinetics in December 2023.
December 2023
This study explores the utility of AI/ML to predict the food effect on oral drug absorption. Drugs with high logP, dose number, and extraction ratio have a higher probability of positive FE, while drugs with low permeability and high efflux saturation index have a greater likelihood of negative FE. Weakly acidic drugs also showed a greater probability of positive FE, particularly at pKa >4.3. The importance of drug properties in predicting FE was ranked as logP, dose number, extraction ratio, pKa, and permeability. Overall, the likelihood or magnitude of FE depends on physiological changes to food intake such as altered bile acid secretion rate, intestinal metabolism, transport kinetics, and gastric emptying time, which should be considered along with drug properties (e.g., solubility, logP, and ionization) in predicting FE of orally administered drugs.
Aarzoo Thakur et al. published, ”Effect of probenecid on blood levels and renal elimination of furosemide and endogenous compounds in rats: Discovery of putative organic anion transporter biomarkers“ in Biochemical Pharmacology in December 2023.
December 2023
Unveiling the endogenous functions of drug metabolizing enzymes and transporters is essential, not solely to comprehend the physiological importance of these proteins but also to uncover potential endogenous biomarkers. These biomarkers hold significance in predicting drug-drug interactions and understanding the impact of interindividual variability. This proof-of-concept metabolomics investigation delves into the identification of potential endogenous substrates of organic anion transporters in the rat kidney.
Dilip Kumar Singh et al. published, ”Characterization of Gla proteoforms and non-Gla peptides of gamma carboxylated proteins: Application to quantification of prothrombin proteoforms in human plasma“ in Analytica Chimica Acta in December 2023.
December 2023
Gamma (γ) carboxylation is an essential post-translational modification in vitamin K-dependent proteins (VKDPs), playing a key role in maintaining critical biological homeostasis. Changes in the abundance or activity of these proteins can have both pharmacological and pathological consequences. Importantly, low levels of fully γ-carboxylated clotting factors can increase plasma des-γ-carboxy precursors, resulting in minimal or no biological activity. Therefore, it is essential to characterize the levels of γ-carboxylation that reflect the active state of these proteins. This research marks the first comprehensive characterization of the mass fragmentation behavior of Gla peptides, which was leveraged to develop an LC-MS/MS method for the simultaneous characterization and quantification of Gla proteoforms and non-Gla peptides.
Sandhya Subash was selected as the Drug Metabolism and Disposition Highlighted Trainee Author for the October 2023 issue
October 2023
Christopher Harding received “Best Poster Presentation” award (third place) in the Pre-doctoral category at the PANWAT 2023 Meeting
September 2023
Christopher Harding presented a poster titled “Effect of rifampicin on global proteomics in HepG2 cells and extracted extracellular vesicles.” at the PANWAT Meeting 2023 and secured third place in the Best Poster Presentation, Pre-doctoral award category. Congratulations!
Kari Gaither received “Best Platform Presentation” award (first place) in the Postdoctoral category at the PANWAT 2023 Meeting
September 2023
Kari Gaither gave a podium presentation on “Global proteomics reveals associations between heavy alcohol consumption and hepatic drug metabolizing enzyme abundance and composition in humans.” at the PANWAT Meeting 2023 and secured first place in the Best Platform Presentation, Postdoctoral award category. Congratulations!
Prasad Lab at PANWAT Meeting 2023
September 2023
Prasad Lab members attended the Pacific Northwest Association of Toxicologists (PANWAT) 2023 Regional Conference in September 2023 and presented their research.
Poster presentation:
- Christopher Harding: “Effect of rifampicin on global proteomics in HepG2 cells and extracted extracellular vesicles.”
Podium presentation:
- Kari Gaither: “Global proteomics reveals associations between heavy alcohol consumption and hepatic drug metabolizing enzyme abundance and composition in humans.“
Aarzoo Thakur received “Best Poster Presentation” award (first place) in the Pre-doctoral category at the ISSX 2023 Meeting
September 2023
Aarzoo Thakur presented a poster titled “Novel metabolomics approach to identify biomarkers of organic anion renal transporters.” at the ISSX Meeting 2023 and secured first place in the Best Poster Presentation, Pre-doctoral award category. Congratulations!
Sandhya Subash received “Best Poster Presentation” award (second place) in the Postdoctoral category at the ISSX 2023 Meeting
September 2023
Sandhya Subash presented a poster titled “Relative expression versus activity factor (REF vs. RAF) to estimate fraction glucuronidation (fgluc) of diclofenac and vorinostat.” at the ISSX Meeting 2023 and secured second place in the Best Poster Presentation, Postdoctoral award category. Congratulations!
Prasad Lab at ISSX Meeting 2023
September 2023
Prasad Lab members attended the 25th North American International Society for the Study of Xenobiotics (ISSX) Meeting in September 2023 and presented their research.
Poster presentation:
- Aarzoo Thakur: “Novel metabolomics approach to identify biomarkers of organic anion renal transporters.”
- Deepak Ahire: “Promiscuity and quantitative contribution of UGT2B17 in drug and steroid metabolism determined by experimental and computational approaches.”
- Kari Gaither: “Quantitative proteomics identifies significant links between hepatic drug metabolizing enzyme abundance and composition and heavy alcohol consumption.“
- Namrata Bachhav: “Can LS180 cells predict metabolism and drug-drug interaction potential of UGT2B17 substrates?“
- Sandhya Subash: “Relative expression versus activity factor (REF vs. RAF) to estimate fraction glucuronidation (fgluc) of diclofenac and vorinostat.”
Talk:
- Dr. Bhagwat Prasad co-chaired a symposium on “Quantitative LC-MS Proteomics” and gave a talk on “What is New in LC-MS Proteomics: Techniques and Applications in IVIVE and Precision Medicine“
Laken Kruger was selected as the Drug Metabolism and Disposition Highlighted Trainee Author for the August 2023 issue
August 2023
Prasad Lab at GRC Meeting 2023
July 2023
Prasad Lab members attended the Drug Metabolism Gordon Research Conference (GRC) in July 2023 and presented their research.
Poster presentation:
- Aarzoo Thakur: “Sex and the kidneys with reference to the FDA Modernization Act 2.0: Are preclinical data of renally-cleared drugs translatable to humans?”
- Dilip Kumar Singh: “Genotype-informed metabolomics approach revealed potentially novel endogenous substrates of UGT2B17”
- Sandhya Subash: “Is human liver microsomes a good in vitro model for dual substrates of CYP and CES enzymes?”
Talk:
- Dr. Bhagwat Prasad: ” Scaling Tissue-Specific Drug Metabolism Using Proteomics-Informed Modeling”
Sandhya Subash et al. published, ”Dissecting parameters contributing to the underprediction of aldehyde oxidase-mediated metabolic clearance of drugs“ in Drug Metabolism and Disposition in July 2023.
July 2023
This study elucidated the plausible reasons for the underprediction of aldehyde oxidase (AO) mediated drug metabolism and provided recommendations to address them. It was demonstrated that integrating protein content and activity differences, accounting for the loss of AO activity, as well as consideration of extrahepatic clearance and additional pathways would improve the in vitro to in vivo extrapolation of AO mediated drug metabolism using physiologically-based pharmacokinetic modeling.
Sheena Sharma et al. published, ”Analysis of the interplay of physiological response to food intake and drug properties in food-drug interactions“ in Drug Metabolism and Pharmacokinetics in June 2023.
June 2023
The effect of food on oral drug absorption is determined by the complex interplay among gut physiological factors and drug properties. The currently used dissolution testing and classification systems (biopharmaceutics classification system, BCS or biopharmaceutics drug disposition classification system, BDDCS) do not account for dynamic changes in gastrointestinal physiology caused by food intake. This study identified key drug properties that influence food effect (FE) using supervised machine learning approaches. The analysis showed that drugs with high logP, dose number, and extraction ratio have a higher probability of positive FE, while drugs with low permeability and high efflux saturation index have a greater likelihood of negative FE. Overall, the likelihood or magnitude of FE depends on physiological changes to food intake such as altered bile acid secretion rate, intestinal metabolism, transport kinetics, and gastric emptying time, which should be considered along with drug properties (e.g., solubility, logP, and ionization) in predicting FE of orally administered drugs.
Dilip Kumar Singh received “Best Poster” award (first place) in the Post-doctoral category at the ASPET 2023 Meeting
May 2023
Dilip Kumar Singh presented a poster titled “High-Resolution Mass Spectrometry Coupled with XCMS Online for High-throughput Detection and Identification of Drug Metabolites” at the American Society for Pharmacology and Experimental Therapeutics (ASPET) Meeting 2023 and secured first place in the Best Poster, Post-doctoral award category. Congratulations!
Prasad Lab at ASPET Meeting 2023
May 2023
Prasad Lab members attended the American Society for Pharmacology and Experimental Therapeutics (ASPET) Meeting in May 2023 and presented their research.
- Dr. Bhagwat Prasad chaired a session on “Advances in ADME and toxicity biomarkers” and gave a talk on “Biomarker of UGT2B17 Variability in Developing Children and Adults“.
- Aarzoo Thakur presented a poster and gave a podium presentation at the Young Investigator Session on “Identification of putative novel biomarkers of organic anion transporter 1 and 3 for the prediction of transporter-mediated drug-drug interactions“.
- Anoud Ailabouni presented a poster and gave a podium presentation titled, “Identification of endogenous biomarkers of renal organic cation transporters in rats by global metabolomics analysis“.
- Dilip Kumar Singh presented a poster on “High-Resolution Mass Spectrometry Coupled with XCMS Online for High-throughput Detection and Identification of Drug Metabolites“.
Prasad Lab at Pfizer PDM Connect Meeting 2023
May 2023
Prasad Lab members attended the Pharmacokinetics Dynamics and Metabolism (PDM) Connect Meeting organized by Pfizer in May 2023 and presented their research.
- Dr. Bhagwat Prasad gave a presentation titiled, “Biomarker of UGT2B17 Variability in Developing Children and Adults“.
- Aarzoo Thakur gave an oral presentation on “Identification of putative novel biomarkers of organic anion transporter 1 and 3 for the prediction of transporter-mediated drug-drug interactions“.
Laken Kruger et al. published, ”Characterization of xenobiotic and steroid disposition potential of human placental tissue and cell lines (BeWo, JEG-3, JAR, and HTR-8/SVneo) by quantitative proteomics“ in Drug Metabolism and Disposition in May 2023.
May 2023
The placenta is a fetal organ that performs critical functions to maintain pregnancy and support fetal development, including metabolism and transport of xenobiotics and steroids between the maternal-fetal unit. In vitro placenta models are used to study xenobiotic and steroid disposition, but how well these models recapitulate the human placenta is not well understood. The abundance of proteins involved in xenobiotic and steroid disposition in human placental tissue was characterized. The proteomics data showed that BeWo and JEG-3 cells are closer to the placental tissue for studying xenobiotic and steroid disposition.
Deepak Ahire successfully defended his doctoral dissertation titled “Promiscuity and Tissue-specific Fractional Contribution of UGT2B17 to Drug and Steroid Metabolism” on 19th April, 2023.
Many Congratulations, Dr. Ahire!
April 2023
Deepak Ahire et al. published, ”Intestinal Metabolism of Diclofenac by Polymorphic UGT2B17 Correlates with its Highly Variable Pharmacokinetics and Safety across Populations“ in Clinical Pharmacology and Therapeutics in April 2023.
April 2023
Although the United States and Europe have shifted to the prescription use of oral diclofenac due to several serious incidences of cardiotoxicity, it is one of the most commonly used over-the-counter (OTC) pain medicines in major parts of the world. The quantitative and tissue-specific contribution of uridine diphosphate-glucuronosyltransferases 17 (UGT2B17) in diclofenac metabolism and pharmacokinetics was elucidated. The developed proteomics-informed physiologically-based pharmacokinetic (PBPK) model explains the reported higher exposure of diclofenac in women consistent with ~ 3-fold lower expression of UGT2B17. Similarly, the in silico predictions also corroborate with the reported higher exposure and lower standard clinical dose of diclofenac in Japanese population. Therefore, variable UGT2B17-mediated metabolism of oral diclofenac is a cause of concern, especially in the developing countries where it is still used as an OTC drug.
Sheena Sharma successfully defended her doctoral dissertation titled “Integration of Mechanisms Affecting the Activity of Drug Metabolizing Enzymes and Transporters to Predict Variability in Oral Drug Absorption” on 28th March, 2023.
Many Congratulations, Dr. Sharma!
March 2023
Laken Kruger successfully defended her doctoral dissertation titled “Characterization of Human Placental Tissue and Cell Lines for their Xenobiotic and Steroid Disposition Potential Through Quantitative Proteomics” on 14th March, 2023.
Many Congratulations, Dr. Kruger!
March 2023
Deepak Ahire et al. published, ”Quantification of Accurate Composition and Total Abundance of Homologous Proteins by Conserved-Plus-Surrogate Peptide Approach: Quantification of UDP Glucuronosyltransferases in Human Tissues“ in Drug Metabolism and Disposition in March 2023.
March 2023
Conventional targeted proteomics utilizes surrogate peptides, which often results in high technical and interlaboratory variability due to peptide-specific digestion leading to data inconsistencies. To address this problem, a novel conserved-plus-surrogate peptide (CPSP) approach was developed for determining the accurate compositions and total or cumulative abundance of homologous UGTs in commercially available pooled human liver microsomes (HLM), human intestinal microsomes (HIM), human kidney microsomes (HKM), and human liver S9 (HLS9) fraction. The CPSP approach could be used for applications in the in-vitro-to-in-vivo extrapolation of drug metabolism and PBPK modeling.
Sheena Sharma et al. published, ”Quantitative Characterization of Clinically Relevant Drug-Metabolizing Enzymes and Transporters in Rat Liver and Intestinal Segments for Applications in PBPK Modeling“ in Molecular Pharmaceutics in February 2023.
February 2023
Rats are extensively used as a preclinical model for assessing drug pharmacokinetics and tissue distribution; however, successful translation of the rat data requires information on the differences in drug metabolism and transport mechanisms between rats and humans. The authors quantified clinically relevant drug-metabolizing enzymes and transporters (DMETs) in the liver and different intestinal segments of Sprague-Dawley rats. The levels of DMET proteins in rats were quantified using the global proteomics-based total protein approach (TPA) and targeted proteomics. To demonstrate the utility of these data, digoxin pharmacokinetics was modeled by integrating protein abundance of P-gp and Cyp3a2 into a physiologically based pharmacokinetic model constructed using PK-Sim software. The model was able to reliably predict the systemic as well as tissue concentrations of digoxin in rats. These findings suggest that proteomics-informed PBPK models in preclinical species can allow mechanistic PK predictions in animal models including tissue drug concentrations.
Sheena Sharma et al. published, ”Interplay of Breast Cancer Resistance Protein (Bcrp/Abcg2), Sex, and Fed State in Oral Pharmacokinetic Variability of Furosemide in Rats“ in Pharmaceutics in February 2023.
February 2023
The interplay of breast cancer resistance protein (Bcrp)-mediated transport, sex, and fed state on furosemide pharmacokinetics in rats was investigated. Based on the obtained results, the potential confounding effect of the Bcrp transporter should be considered when furosemide is used as a clinical probe of renal organic anion transporter-mediated drug–drug interactions.
Laken Kruger et al. published, ”An optimized proteomics-based approach to estimate blood contamination and cellular heterogeneity of frozen placental tissue” in Placenta in December 2022.
December 2022
An optimized proteomics-based approach to estimate blood contamination and cellular heterogeneity of placental tissues was developed. This approach has the potential to address technical variability in placenta proteomics analysis, which can be extended to other highly perfused and heterogenous tissues.
Sheena Sharma was selected as the Drug Metabolism and Disposition Highlighted Trainee Author for the December 2022 issue
December 2022
Sheena Sharma received “Best Poster” award (third place) at the GPEN conference 2022
October 2022
Sheena Sharma presented a poster on the topic “Poor and Variable Oral Bioavailability of Dimethandrolone, an Investigational Male Hormonal Contraceptive, is Likely Associated with UGT2B17 Mediated First-Pass Metabolism” at the Globalization of Pharmaceutics Education Network (GPEN) Conference 2022 and secured third place in the Best Poster award category. Congratulations!
Deepak Ahire received “Best Presentation” award (second place) at the ISSX Meeting 2022
September 2022
Deepak Ahire gave an oral presentation on “Quantification of absolute compositions and total abundance of homologous proteins using the novel conserved-plus-surrogate peptide (CPSP) approach: Application in the quantification of UDP glucuronosyltransferases (UGTs) ” at the International Society for the Study of Xenobiotics (ISSX) Meeting and secured second place in the Best Presentation award category. Congratulations!
Prasad Lab at ISSX Meeting 2022
September 2022
PhD and Postdoctoral students from Prasad Lab attended the International Society for the Study of Xenobiotics (ISSX) Meeting in September 2022 and presented their research.
Prasad Lab at GRC 2022
July 2022
Deepak Ahire (third year graduate student) and Sandhya Subash (post-doctoral fellow) from Prasad Lab attended and presented their research work at the Gordon Research Conference (GRC) in July 2022.
Prasad Lab at ASPET Annual Meeting 2022
April 2022
Students from Prasad Lab attended the American Society for Pharmacology and Experimental Therapeutics (ASPET) Annual Meeting in April 2022 and presented their research.
Deepak Ahire was selected as the Drug Metabolism and Disposition Highlighted Trainee Author for the March 2022 issue
March 2022
Vijay Mettu was selected among the top 5 finalists to compete for the poster award in the Postdoctoral category at the 24th North American ISSX Meeting, September 13 – 17, 2021.
August 2021
Vijay Mettu presented “Deeper insight into the chromatographic and mass fragmentation behaviors of endogenous steroids for their specific quantification by LC-MS/MS” at the 2021 ISSX meeting. Congratulations!
The Prasad lab received a US Patent for developing Methods for Treating Testosterone Deficiency in Men and Methods for Precise Dosing of UGT2b17 Substrate Drugs.
July 2021
Bhagwat Prasad, Abdul Basit, Haeyoung Zhang, and John K Amory contributed to this patent. Congratulations to all!
Deepak Ahire received the best poster award in the Student Category at the Society for the Study of Xenobiotics-India 2021.
July 2021
Deepak Ahire received the best poster award in the Graduate Student category on “Human liver microsomes (HLM) overpredict interindividual variability in drug-metabolizing enzymes: implications for PBPK modeling”. Congratulations!
Sheena Sharma and Bhagwat Prasad published a research article, “Meta-Analysis of Food Effect on Oral Absorption of Efflux Transporter Substrate Drugs: Does Delayed Gastric Emptying Influence Drug Transport Kinetics?” in the Pharmaceutics on July 7, 2021.
July 2021
This article belongs to the Special Issue Challenges and Perspectives of Drug Transporters: Where Do We Go from Here? In the paper, a systematic analysis of reported clinical food-effect (FE) studies on 311 drugs was performed and the association of the efflux transport efficiency was investigated on the food-effect magnitude. The key observation was that the drugs with a high potential for efflux transport were associated with negative food-effect.
Masud Parvez was selected as the Drug Metabolism and Disposition Highlighted Trainee Author for August 2021.
June 2021
This feature of the journal is designed to highlight emerging scientific talent in the field of pharmacology. Congratulations, Dr. Masud Parvez !!
Deepak Ahire received second prize in the Drug Metabolism and Disposition (Student) category at the American Society for Pharmacology and Experimental Therapeutics (ASPET) Annual Meeting at Experimental Biology 2021.
April 2021
Deepak Ahire received second place in the Graduate Student category on “Inter-individual variability and differential tissue abundance of mitochondrial amidoxime reducing component 1 (mARC1) enzyme in human”. He is featured in the PHARMACY AND PHARMACEUTICAL SCIENCES newsletter. Kudos to him!!
Masud Parvez received third place in the Drug Metabolism and Disposition (Postdoctoral) category at the American Society for Pharmacology and Experimental Therapeutics (ASPET) Annual Meeting at Experimental Biology 2021.
April 2021
Md Masud Parvez got third place in the Postdoctoral category on “Proteomics-informed scaling of irinotecan metabolism, transport, and gut microbial activation explain its intestinal toxicity after intravenous dose”. He is also featured in the PHARMACY AND PHARMACEUTICAL SCIENCES newsletter. Congratulations!!
Deepak Ahire et al. published, “Ultrasensitive quantification of drug-metabolizing enzymes and transporters in small sample volume by microflow LC-MS/MS” in the Journal of Pharmaceutical Sciences on 27th March 2021.
March 2021
We developed an ultrasensitive method that relies on an optimized sample preparation approach involving acetone precipitation coupled with a microflow-based liquid chromatography-tandem mass spectrometry (μLCMS/ MS) for the DMET quantification using limited sample volume or protein concentration, i.e., liver tissues (1-100 mg), hepatocyte counts (~4000 to 1 million cells), and microsomal protein concentration (0.01-1 mg/ml). The method was applied to quantify DMETs in differential tissue S9 fractions (liver, intestine, kidney, lung, and heart) and cryopreserved human intestinal mucosa (i.e., CHIM). The method successfully quantified >75% of the target DMETs in the trypsin digests of 1 mg tissue homogenate, 15,000 hepatocytes, and 0.06 mg/ml microsomal protein concentration.
Revathi Chapa et al. published, ”Contribution of Uptake and Efflux Transporters to Oral Pharmacokinetics of Furosemide” in ACS Omega on 15th December 2020.
December 2020
Furosemide tablet formulation exhibits variable pharmacokinetics (PK) with bioavailability ranging from 10 to almost 100%. To explain the variable absorption, we integrated the physicochemical, in vitro dissolution, permeability, distribution, and the elimination parameters of furosemide in a physiologically-based pharmacokinetic (PBPK) model.
Siavosh Naji-Talakar et al. published, “Potential implications of DMET ontogeny on the disposition of commonly prescribed drugs in neonatal and pediatric intensive care units” in Expert Opinion on Drug Metabolism & Toxicology on 1st December 2020.
December 2020
We reviewed the top 29 small molecule drugs prescribed in neonatal and pediatric intensive care units and compiled the mechanisms of their metabolism and excretion. The ontogeny of Phase I and II drug-metabolizing enzymes and transporters (DMETs), particularly relevant to these drugs, are summarized. The potential effects of DMET ontogeny on the metabolism and excretion of the top pediatric drugs were predicted. The current regulatory requirements and recommendations regarding the safe and effective use of drugs in children are discussed. A few representative examples of the use of ontogeny-informed physiologically-based pharmacokinetic (PBPK) models are highlighted.
Sheena Sharma, Deepak Ahire and Bhagwat Prasad published, “Utility of Quantitative Proteomics for Enhancing the Predictive Ability of PBPK Models Across Disease States”, in the Journal of Clinical Pharmacology on 7th November 2020.
November 2020
We summarized these data including the available immunoquantification or mRNA levels of DMET proteins (healthy vs disease states) in extrahepatic tissue and discuss the potential applications of DMET abundance data in enhancing the capability of PBPK modeling in predicting drug disposition across disease states. Successful examples of PBPK modeling that integrate differences in DMET proteins between healthy and disease states are discussed.
Congratulations to Nandini Katti for receiving funding from the American College of Clinical Pharmacy Foundation Futures Grants Program for a research project titled, “Association of steroidal urinary metabolites in adolescent polycystic ovary syndrome”.
November 2020
Abdul Basit et al. published, “Characterization of Differential Tissue Abundance of Major Non-CYP Enzymes in Human“, in Molecular Pharmaceutics on 21st September 2020.
September 2020
The protein abundances of eighteen non-CYP DMEs (AO, CES1 and 2, ten UGTs, and five SULTs) were quantified across five different human tissues. These differential tissue abundance data can be integrated into physiologically based pharmacokinetic (PBPK) models for the prediction of non-CYP drug metabolism and toxicity in hepatic and extrahepatic tissues.
Haeyoung Zhang, Abdul Basit and Bhagwat Prasad published a book chapter, “Quantifying drug metabolizing enzymes and transporters by LC-MS/MS proteomics” in July 2020.
July 2020
Book title: Identification and Quantification of Drugs, Metabolites, Drug Metabolizing Enzymes, and Transporters. https://www.sciencedirect.com/book/9780128200186/identification-and-quantification-of-drugs-metabolites-drug-metabolizing-enzymes-and-transporters
Prasad lab members think working from home can’t make them any less productive
April 2020
Yes, COVID-19 cannot affect our determination to pursue our training, teaching, and research!
Prasad lab initiates COVID-19 Research Collaboration
April 2020
Anyone interested in a collaboration, please contact Bhagwat Prasad.
PRINCE teleconference meeting held in Prasad lab, WSU Spokane on March 27
March 2020
The meeting discussed PRINCE 2.0 project with collaborators from Genentech, Gilead, and Merck in a teleconference meeting on March 27.
Prasad lab welcomes Dr Vijay Mettu as a new Research Associate!
March 2020
Dr Mettu has an experience of 15 years of working in drug discovery programs, and in vitro and in vivo DMPK studies. Previous to joining Prasad lab in WSU Spokane, he has worked as an in vivo lead and DMPK program representative in GlaxoSmithKline Singapore and DMPK manager in Agency for Science, Technology and Research (A*STAR), Singapore.
2020 GRSA Science Bites-3 min Thesis Competition Winner
February 2020
Sheena Sharma won second prize in the WSU Graduate Research Student Association (GRSA) 2020 3-minute thesis competition. Congrats!
2020 WSU Pharm Sci Best Poster Award
February 2020
Dr Abdul Basit earned the best poster award in the WSU Pharm Sci poster presentation. Kudos!
The Prasad lab wishes everyone very happy holidays 2019!
December 2019
Picture courtesy: Dr Abdul Basit
Dr Prasad presented a talk on ‘Quantitative Proteomics in Precision Medicine’ in Pharmacology 2019 meeting, Edinburgh UK (Dec 11-17)
December 2019
The presentation was held in the session entitled ASPET/BPS Joint Symposium on Precision Medicine: Progress and Challenges.
PRINCE teleconference meeting held in Prasad lab, WSU Spokane on Dec 3
December 2019
The meeting discussed project progress and specific aims for the coming year with collaborators from Genentech, Gilead and Merck.
Prasad lab research on precision medicine for children got featured in the WSU post
December 2019
The article talked about the importance of finding the precise dosing for pediatric population to avoid toxicity concerns.
Dr Prasad addressed PharmD and PhD students in an interactive talk on ‘Revolutionizing pharmaceutical development with physiologically based pharmacokinetic systems’ at WSU Spokane
November 2019
Dr Prasad talked about the emerging importance of PBPK in regulatory submissions and pharmaceutical drug development. The students were motivated to pursue unconventional pharmacy jobs in the future to fill the global need for better health care options.
Prasad lab welcomes Dr Masud Parvez as a new Research Associate!
November 2019
Dr Parvez has a good experience of working on projects related to transport assays and the prediction of pharmacokinetics in special populations using PBPK modeling. Previous to this, he has worked in Shin lab as a Research Assistant Professor at INJE University, Busan, South Korea.
Dr Prasad presented a talk on ‘Role of UGTs and drug transporters in testosterone disposition’ in the first annual symposium on Development, Disease and Reproduction at Center for Reproductive Biology, WSU Pullman
October 2019
During this oral presentation, Dr Prasad talked about testosterone homeostasis in the human body.
Dr Prasad presented a webinar on ‘Importance of Quantitative Traning to Address Rigor and Reproducibility in DMPK/PD Research’ in the ISSX Webinar Series
October 2019
In this webinar, Dr Prasad shared why quantitative training is important for different areas of DMPK/PD discipline through case studies. Particularly, examples justifying how the lack of clear understanding of quantitative methods can affect rigor in DMPK/PD research were illustrated to the attendees.
Successful inauguration of LC-MS facility in Prasad lab
September 2019
The lab has initiated the facility for LC-MS analysis. Waters Xevo-TQ-XS MS with IonKey source and microflow LC will be used to perform targeted proteomics and metabolomics analysis of DMET proteins and biomarkers. Thermo’s Q-Exactive-HF MS with nano-flow LC will be utilized for untargeted proteomics and metabolomics analysis.
Prasad lab moved to WSU, Spokane, WA
August 2019
Prasad lab has moved to the College of Pharmacy and Pharmaceutical Sciences (CPPS) at Washington State University, Spokane, WA from the University of Washington, Seattle, WA in 2019. The lab is continuing research projects focusing on prediction of drug disposition using omics-informed PBPK modeling approach.
Prasad lab got featured in the cover page of August 2019 issue of Drug Metabolism and Disposition journal
August 2019
The featured article talks about kidney cortical transporter expression across species using quantitative proteomics.
PRINCE (Proteomics-based Research Initiative on Non-CYP enzymes) consortium sponsored by Genentech, Gilead and Merck started in WSU
August 2019
The PRINCE (Proteomics-based Research Initiative for Non-CYP Enzymes) program is a research collaboration between the Prasad lab at Washington State University and the pharmaceutical industry to elucidate role of non-cytochrome P450 (non-CYP) enzymes in disposition, efficacy and toxicity of drugs.
Prasad lab received funding from Bristol Myers Squibb (BMS) on the characterization of mARC (mitochondrial amidoxime reducing complex) protein component
August 2019
The “mitochondrial Amidoxime Reducing Component” (mARC) is the newly discovered fourth molybdenum enzyme in mammals and is involved in reduction of many N-hydroxylated nucleobases and nucleosides and in lipid metabolism.
Members from Prasad lab brought laurels at 12th International ISSX Meeting, held in Portland, OR (July 28–31)
July 2019
The award recipients from Prasad lab were:
Graduate/Predoctoral Awards
• First place: Haeyoung Zhang for the poster entitled “Is urinary testosterone glucuronide a potential biomarker for UGT2B17 ontogeny in ages 7 to 18 years?”
• Second place: Revathi Chapa for the poster entitled “Investigating the role of drug transporters in furosemide absorption, food-effect and elimination using a proteomics informed-mechanistic PBPK modeling approach.”
Postdoctoral Awards
• First place: Naveen Neradugomma and Abdul Basit for the poster entitled “Characterization of differential tissue abundance of major non-CYP enzymes in human.”