Research Interests:
Dr. Unadkat's research interests are in elucidating mechanisms of
disposition of drugs used in the treatment of AIDS and associated
opportunistic infections. In particular, his laboratory conducts
research on transport of anti-AIDS drugs across the placenta, intestine
and the blood-brain/CSF barrier. These studies have focused
on mechanisms of transport by two major families of transporters
namely the nucleoside transporters and the ABC transporters.
Dr. Unadkat's laboratory is also involved in determining the mechanisms
of metabolism of anti-AIDS drugs, including drug interaction. Translation
of research findings from in vitro to in vivo is a key element in
these research activities. Dr. Unadkat currently heads up
one of eleven Specialized Centers of Research (SCOR) nationwide
that focus on research on Women’s Health. This SCOR is focused
on understanding the mechanistic basis for changes in expression
and activity of transporters and metabolic enzymes during pregnancy.
Dr. Unadkat has published more than 85 research papers. His laboratory
has received continuous NIH funding since 1986. Dr. Unadkat is a
fellow of AAPS and the founding member and former chair of the focus
group on Drug Transport and Uptake. He has been involved in organizing
several events at the AAPS annual meeting. Dr. Unadkat is a former
Associate Editor for the Journal of Pharmaceutical Sciences, an
editorial board member of the Journal of Pharmaceutical Sciences
and an Editor for AAPS Pharm Sci. Dr. Unadkat has served on several
NIH grant review committees and is a former member of the Pharmacology
Study Section. He has refereed papers for numerous biochemical,
pharmacology and pharmaceutical science journals. Dr. Unadkat has
organized or co-organized various conferences and meetings including
the 1st AAPS Workshop on Drug Transport, Georgia, 2003, the 1st
EUFEPS conference on Drug Transporters: Integrative Approaches in
ADME Research, Copenhagen, 2004 and the AAPS Workshop on Pharmacokinetics
and Pharmacodynamics of Drugs in Pregnant and Lactating Women: Issues
and Challenges, Virginia, 2004, the 1st EUFEPS conference on Drug
Transporters: Integrative Approaches in ADME Research, Copenhagen,
2004, and the AAPS Workshop on Drug Transporters in ADME: From the
Bench to the Bedside, Parsippany, 2005. Dr. Unadkat is part of the
organizing committee of the Biomedical Transporter Meeting and the
EUFEPS conference on drug transporters, conferences that are held
every other year in Switzerland (odd years) and Denmark (even years)
respectively.
Ongoing Research:
Imaging P-gp Activity at Human Blood-brain
Barrier and at the Placental-blood Barrier
Using 11C-verapamil
and positron emission
tomography
(PET) we are imaging P-gp activity,
in vivo, in various tissues in human and animals.
CNS Drug Delivery Strategies Targeting
the HIV Sanctuary
The major goal of this project is to use a product
and chemical inhibition of P-gp to enhance the concentration of
ddI and indinavir in the CNS of the nonhuman primate, M. nemestrina
.
Mechanisms
By Which Maternal and Fetal Drug Exposure Is Altered During Pregnancy
Dr. Unadkat is the program director of this center
grant (SCOR) which is made up of three projects, one of which is
based at the Medical College of Georgia.
Project I Title: Changes in Hepatic and Intestinal P-glycoprotein
and CYP3A Activity During Pregancy; PI Jashvant D. Unadkat, Ph.D.
Studies will be conducted in pregnant women and macaques using
digoxin and midazolam or anti-HIV protease inhibitors.
Project II Title: The Breast Cancer Resistance Protein
(BCRP) in Pregnancy: Activity, Expression and Regulation;
PI Qingcheng Mao, Ph.D., JD Unadkat (Co-PI)
The activity, expression, and regulation of BCRP and P-gp will
be determined in mice and in human placenta.
Mechanisms of Uptake of Nucleosides and
Nucleoside Drugs in the Human Intestine
Nucleoside transporters expressed in the intestine
will be characterized in terms of structure-function studies and
cellular localization.
Mechanism of Inductive Drug-Interactions with Anti-HIV Protease
Inhibitors
The long-term objectives of this project are
to characterize the spectrum of induction of hepatic and intestinal
CYP enzymes and multidrug resistance transporters by the HIV protease
inhibitors, both in vitro and in vivo, and to determine whether
those changes in steady-state CYP/transporter expression involve
transcriptional activation events mediated by the PXR, CAR, or VDR
nuclear receptors.
Biography
Jash Unadkat, Ph.D. is a Professor of Pharmaceutics, School of Pharmcy
and a research affiliate of the Washington National Primate Research
Center, Center for Human Development and Disability and the Center
for AIDS and STD at the University of Washington, Seattle. Dr. Unadkat
received his Bachelors degree in Pharmacy (B.Pharm.) from the University
of London (1977) and his Ph.D. in Pharmacy from the University of
Manchester (1982). Dr. Unadkat joined the University of Washington
after postdoctoral training in the Division of Clinical Pharmacology,
University of California at San Francisco (1982-85). |
