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Membrane transporters play an important role in maintaining the homeostasis and physiological functions of nutrients, ions, and hormones. In addition, they also contribute significantly to the absorption, distribution and elimination of therapeutic agents and their metabolites. Many of these transporters are expressed and localized in the intestine, liver, kidney, and blood-brain barrier (BBB). Interruption of the transporter activity due to either transporter interaction or gene mutation may alter the systemic pharmacokinetics and tissue exposure of target drugs, therefore, can potentially lead to organ toxicities. In this presentation, several examples of transporter associated organ toxicity resulting from transporter gene deficiency or functional inhibition in the liver, kidney and intestine will be discussed.
Yan Zhang, Ph.D.
Senior Senior Principal Investigator , Incyte Corporation
Dr. Zhang is a Senior Principal Investigator in the Department of Drug Metabolism, Pharmacokinetics & Clinical Pharmacology (DMPK/CP) at Incyte Corporation in Wilmington, Delaware. She received her M.Sc. degree from the Pharmacology Department at South Dakota State University and her PhD from the Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center. She completed her post-doctoral training in the PDM Department at Pfizer in Ann Arbor, Michigan. The research focus of her PhD program and her post-doctoral training was on the roles of efflux transporters, especially P-gp and MRPs, in the CNS drug delivery and brain penetration. She has fifteen years’ experiences in oncology drug discovery and close to twenty years’ experience in the field of drug transporters. Dr. Zhang is the author of over 40 peer-reviewed publications, book chapters, and abstracts. She also is a committee member of the CPLG Transporter Working Group of the IQ Consortium. She is currently leading the drug absorption and transporter strategies to support Incyte discovery and development programs. Research interests include the pharmacokinetics and pharmacodynamics, transporter mediated toxicity and drug-drug interactions, and in vitro/in vivo transporter correlation.