| |
|
Professor and Chair
Department of Biomedical Sciences
Tufts University School of Veterinary Medicine
200 Westboro Road
North Grafton, MA 01536
Phone: 508-839-8788
Email: Sawkat.Anwer@tufts.edu
Research Interests:
Dr. Anwer's research objective has been to more clearly define
cellular mechanisms involved in hepatic solute transport and bile
formation. Solute transport from blood to bile is an important function
of the liver, with accumulation of (otherwise excreted) endogenous
and exogenous solutes in blood being a common feature of cholestasis.
The major focus of his current research is to define the role of
phosphoinositide-3-OH kinase (PI3K), protein kinase B (PKB), mitogen
activate protein kinase (MAPK) and protein phosphatases (PP2A and
PP2B) in hepatic bile acid transport from blood to bile and apoptosis.
Sinusoidal Na+/taurocholate (TC) cotransport is mediated via Na+/TC
cotransport peptide (ntcp), and canalicular ATP-dependent bile acid
transport is mediated via a sister P-glycoprotein (spgp). Hypotheses
being tested are: 1) The short term regulation of Na+/TC cotransport
by cAMP involves translocation of ntcp to the sinusoidal membrane;
the translocation requires PI3K/PKB activity, involves vesicular
transport and is facilitated by dephosphorylation, a process stimulated
by PP2A and PP2B, and inhibited by MAPK, and 2) PI3K and MAPK stimulate
canalicular ATP-dependent bile acid transport by translocating spgp
to the canalicular membrane. Studies are conducted in isolated perfused
rat livers, rat hepatocytes and plasma membrane vesicles, Huh7 cells
stably transfected with Ntcp and in Cos cells.
Recent Publications:
Cullen KA, McCool J, Anwer MS, Webster CRL. Activation of cAMP-guanine
exchange factor confers PKA-independent protection from hepatocyte
apoptosis. Am J of Physiology-Gastrointestinal and Liver Physiology
287:G334-343, 2004.
McConkey M, Gillin H, Webster CRL, Anwer MS. Cross-talk between
protein kinases C zeta and B in cyclic AMP-mediated sodium taurocholate
co-transporting polypeptide translocation in hepatocytes. J Biol
Chem 279: 20882-20888 2004.
Webster CRL, Srinivasulu U, Ananthanarayanan M, Suchy FJ, Anwer
MS. Protein kinase B/Akt mediates cAMP- and cell swelling-stimulated
Na+/taurocholate cotransport and Ntcp translocation. J Biol Chem
277:28578-28583, 2004.
Webster CRL, Blanch C, Anwer MS. Role of PP2B in cAMP-induced dephosphorylation
and translocation of NTCP. Hepatology Am J of Physiology-Gastrointestinal
and Liver Physiology 281:G44-50, 2002.
|
|