Xin Chen is a Ph.D. candidate co-mentored by Dr. Qingcheng Mao and Dr. Jashvant D. Unadkat. He has investigated whether THC and its major metabolites are substrates/inhibitors of human P-gp/BCRP at pharmacologically relevant concentrations (Chen et al., DMD, 2021). Xin has also further investigated if mouse P-gp/Bcrp could alter the disposition of cannabinoids during pregnancy. These results will be highly valuable for a mechanistic and profound understanding of the disposition of cannabinoids, which is crucial to precision medicine and optimization of dosing regimens of drugs for better efficacy and reduced toxicity during pregnancy.
Aditya R. Kumar is a PhD student in the Unadkat lab. He has quantified the metabolism of THC and 11-OH-THC in human intestinal, lung, and fetal liver metabolism (Kumar AR et al., DMD, June 2022). Adi has also characterized transplacental transport of THC in the perfused human placenta. He aims to characterize the placenta transfer of the metabolites, 11-OH-THC and COOH-THC. These data will now be populated into a maternal-fetal physiologically based pharmacokinetic (m-f-PBPK) model to predict fetal exposure to THC throughout pregnancy. The m-f-PBPK model will be validated with maternal plasma, umbilical venous plasma, and tissue currently being collected from women using cannabis during pregnancy. Prediction of fetal exposure to THC is important to conduct future preclinical studies at these physiologically relevant concentrations and we can determine the risks to fetal development from prenatal cannabis use.
Aurora Authement is a PhD student in the Isoherranen lab. She has characterized the cytosolic and microsomal enzymes which metabolize 11-OH-THC to 11-COOH-THC. Aurora also coordinates a clinical study that will assess how relevant pregnancy hormones, estradiol and cortisol, impact THC disposition. Through this study, she will determine the change in THC plasma exposure after each hormone treatment. The data from this study will be modeled to estimate the effect of gestational-age dependent changes on THC disposition and predict prenatal cannabis usage.
King Yabut is a 5th year PhD student in the Isoherranen lab. His thesis work is focused on investigating the role of intracellular lipid binding proteins in drug disposition. He is specifically working on liver fatty acid binding protein (FABP1) and its role in THC metabolism by human liver cytochrome P450s (CYPs). Using in vitro binding and metabolic assays with recombinant proteins and magnetic silica bead technology, King’s work has demonstrated that FABP1 binds to sequester THC in metabolic studies with CYP2C9 but does not alter THC metabolism contrary to what has been previously shown in FABP1 knock out animal models. His work sheds light on the mechanisms of cellular protein binding of THC and how this process should be considered for improved in vitro to in vivo predictions for THC disposition.
Mayur K. Ladumor, Ph.D., is a senior postdoctoral fellow in the Department of Pharmaceutics at the School of Pharmacy, University of Washington, Seattle. Dr. Ladumor received his Diploma (D. Pharm., 2010) and Bachelor (B. Pharm., 2013) degrees in Pharmacy from the L. M. College of Pharmacy, Gujarat Technological University in Gujarat, India, and his Masters (M.S., 2015) and Doctoral (Ph.D., 2019) degrees in Pharmaceutical Analysis from the National Institute of Pharmaceutical Education and Research (NIPER) in Punjab, India. In 2019, he joined as a postdoctoral fellow in Prof. Jash Unadkat Laboratory at the University of Washington. Dr. Ladumor’s research focuses on translational sciences, with an emphasis on predicting in vivo human drug exposure/response and drug-drug interactions in healthy and special populations (e.g., children, pregnant women, and disease) using laboratory-based in vitro and physiologically-based mathematical models. His research has the potential to develop safe and effective drug dosage regimens, reduce or replace preclinical and clinical trials, and reduce drug development costs and time.
He has developed a physiologically based pharmacokinetic (PBPK) model to predict local respiratory tract tissue and systemic blood drug concentrations in humans following inhalation administration through a cigarette or inhaler. He now aims to apply this developed model to predict cannabis exposure and response after inhalation, followed by model validation using in vivo observed data. Once validated, it will be linked to an existing maternal-fetal PBPK model developed at the Unadkat Laboratory to predict cannabis exposure in maternal and fetal tissues following inhalation.
He is a member of the International Society for the Study of Xenobiotics (ISSX), the American Association of Pharmaceutical Scientists (AAPS), and the American Society for Clinical Pharmacology and Therapeutics (ASCPT). He published over 15 research articles and presented over 25 posters at scientific conferences in the field of Pharmaceutical Sciences.