Vishakha Bhave, B. Pharm., PhD
Assistant Professor of Pharmaceutical Sciences
Post-doctoral fellowship: University of Pittsburgh School of Medicine, 2013
PhD, University of Louisiana at Monroe, 2007
Baccalaureate in Pharmacy: Mumbai University, 2002
Dr. Bhave feels that the effectiveness of the material taught determines the success
of a teacher. Her efforts as a teacher are directed towards making the subject matter
interesting and relevant to the students. She hopes that the students can apply what
they learn here for the betterment for their careers. Her primary teaching interests
lie in the area of Pharmacology and Toxicology.
Research in Dr. Bhave’s lab focuses on studying the role of stem cell factors (reprogramming
factors) in the transdifferentiation of hepatocytes to biliary epithelial cells. Transdifferentiation
is a process wherein a differentiated cell dedifferentiates and redifferentiates into
another cell type. This process is well documented in humans and rodents. Transdifferentiation
of hepatocytes to biliary epithelial cells (BEC) provides a rescue mechanism in liver
diseases when the biliary compartment fails to regenerate by itself in order to compensate
for the lost structure and function. Human chronic biliary liver diseases (Primary
biliary cirrhosis and primary sclerosing cholangitis) characterized by progressive
BEC degeneration and rodent models of transdifferentiation exhibit formation of intermediate
hepatobiliary cells expressing both hepatocytic and biliary specific markers indicating
transdifferentiation of hepatocytes to BEC. The mechanisms underlying such transdifferentiation
are not known. Recently, we reported that Oct3/4, Nanog, and Klf4 (genes known to
maintain pluripotency of stem cells and their ability to differentiate into various
cell lineages, referred to as “reprogramming factors”) are expressed by proliferating
primary cultured hepatocytes and in vivo following 70% partial hepatectomy. In vitro,
their inhibition resulted in decreased proliferation and increased apoptosis, signifying
their role in survival and proliferation; however, whether this upregulation also
enables transdifferentiation to BEC is not known. Our hypothesis is that induced expression
of reprogramming factors is responsible for the ability of hepatocytes to transdifferentiate
into BEC (a process involving somatic cell reprogramming). This research will identify
a novel mechanism for somatic cell reprogramming during transdifferentiation that
could potentially be utilized to postpone/prevent liver fibrosis and therapeutic transplantation
in chronic biliary liver diseases.
Society of Toxicology Mechanisms Specialty Section Carl Smith Graduate student Award
for meritorious research, March 2007.
Society of Toxicology Colgate Palmolive Student Research Training Award in Alternative
Methods in Toxicology, March 2005.
Sir Ratan Tata merit scholarship for undergraduate studies in Pharmacy, February 2000.
Donthamsetty S, Bhave V. S., Mars W., Orr A., Haynes M. M., Wu C., and Michalopoulos
G. K. Role of PINCH-Rsu-1 Complex in Regulating Liver size and tumorigenesis, PLOS
Bhave V. S., , Donthamsetty S., Zhang X., Tan L., Lou J., Bowen B.W., Michalopoulos
G.K. Regulation of liver growth by Glypican 3, CD81, Hedgehog, and Hhex. Am J Pathol,
183: 153-159, 2013.
Bhave V. S., Shirish Paranjpe, William C. Bowen, Shashikiran Donthamsetty, Aaron W.
Bell, Jaspal S. Khillan, and George K. Michalopoulos. Genes inducing iPS phenotype
play a role in hepatocyte survival and proliferation in vitro and liver regeneration
in vivo. Hepatology, 54(4):1360-1370, 2011.
Bhave, V. S., Donthamsetty, S., Latendresse, J. R., Cunningham, M., and Mehendale.
H. M. Absence of hepatic COX-2 exacerbates sPLA2-mediated progression of hepatotoxicity
initiated by acetaminophen. Toxicol. Appl. Pharmacol. 251: 173-180, 2011.
Bhave, V. S., Donthamsetty S., Latendresse J. R., Muskhelishvili L, and Mehendale
H. M. Secretory phospholipase A2 mediates progression of acute liver injury in the
absence of sufficient COX-2. Toxicol. Appl. Pharmacol., 228(2):225-38, 2008.
Bhave, V. S., Donthamsetty S., Latendresse J. R., and Mehendale H. M. Inhibition of
COX-2 aggravates secretory phospholipase A2-mediated progression of acute liver injury.
Toxicol. Appl. Pharmacol., 228(2):239-46, 2008.
Limaye P. B., Bhave V. S., Palkar P. S., Apte U. M., Sawant S. P., Yu S., Latendresse
J. R., Reddy J. K., and Mehendale H. M. Upregulation of calpastatin in regenerating
and developing livers: Role in resistance against hepatotoxicity. Hepatology, 44(2):379-388,
Genes Inducing iPS Phenotype Play a Role in Normal Hepatocyte Growth and Liver Regeneration.
McGowan Institute of Regenerative Medicine Annual Retreat. March 7-10, 2010, Invited
Secretory phospholipase A2 mediates progression of acute liver injury in the absence
of sufficient COX-2. SFRR- Society for Free Radical Research Satellite Meeting, Feb
11-12, 2008, India. Session title: Free radicals and antioxidants in human health,
gene regulation and signal transduction, Invited talk.
Vishakha S. Bhave, William C. Bowen, Shashikiran Donthamsetty, Aaron Bell, and George
K. Michalopoulos. Role of reprogramming factors in transdifferentiation of hepatocytes
to biliary epithelial cells. FASEB J. 2012 26:274.4.
Vishakha S. Bhave, Shirish G. Paranjpe, William C. Bowen, Shashikiran Donthamsetty,
Aaron Bell, Jaspal Khillan, and George K. Michalopoulos. Genes Inducing iPS Phenotype
Play a Role in Hepatocyte Survival and Proliferation In Vitro and Liver Regeneration
In Vivo. FASEB J. 2011 25:115.2.
Vishakha S. Bhave, William C. Bowen, Shirish G. Paranjpe, Shashikiran Donthamsetty,
and George K. Michalopoulos. Inhibition of RE-1 silencing transcription factor (REST)
inhibits survival and proliferation of primary hepatocytes under the influence of
hepatocye growth factor (HGF) and epidermal growth factor (EGF). FASEB J. 2010 24:236.4
Volunteer & Leadership
2005-2006: Student Representative of the South Central Chapter of Society of Toxicology
2007-2008: Student Representative of Risk Assessment Specialty Section (RASS) of SOT
Reviewer, Toxicology and Applied Pharmacology (TAAP)
Reviewer, BMC cancer
Reviewer, Journal of Cell Science
Reviewer, American Journal of Pathology (AJP
Reviewer, Toxicological Sciences
Reviewer, Liver international
Ongoing Research Support
Center for Chronic Diseases of Aging (CCDA) grant
Funding period: 07/2013- 06/2014
Grant Title: Role of reprogramming factors in transdifferentiation of hepatocytes
to biliary epithelial cells.
Award amount: $15,600
Completed Research Support
University of Pittsburgh, Department of Pathology Post-doctoral Research Training
Funding period: 07/2012 – 06/2013
Grant Title: Role of stem cell/reprogramming factors in transdifferentiation of hepatocytes
to biliary epithelial cells.
Award amount: $10,000
Society of Toxicology Colgate Palmolive Student Research Training Grant In alternative
Methods in Toxicology
Funding period: 03/2005-02/2006
Grant Title: Role of Calpastatin in resisting calpain-induced injury in hepatocytes.
Award amount: $3,500
Bhave V. S., , Donthamsetty S., Zhang X., Tan L., Lou J., Bowen B.W., Michalopoulos G.K. Regulation
of liver growth by Glypican 3, CD81, Hedgehog, and Hhex. Am J Pathol, 183: 153-159,
2013. This publication (PMID: 23665349) is selected to be featured in ‘Hot off the
Press’ section of American Society of Investigative Pathology (ASIP) November 2013