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  Academic Programs

PCOM School of Pharmacy Faculty

Vishakha Bhave, B. Pharm., PhD

Assistant Professor of Pharmaceutical Sciences

Contact
Ph: 678-407-7344
FX: 678-407-7347
E-mail: vishakhabh@pcom.edu

Education

Post-doctoral fellowship: University of Pittsburgh School of Medicine, 2013
PhD, University of Louisiana at Monroe, 2007
Baccalaureate in Pharmacy: Mumbai University, 2002

Narrative

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.

 

Honors/Awards

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.

 

Selected Publications

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 One, 2013.

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, 2006.

 

Selected Presentations

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 talk.

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

Professional Societies

2005-2006: Student Representative of the South Central Chapter of Society of Toxicology (SOT)

2007-2008: Student Representative of Risk Assessment Specialty Section (RASS) of SOT

 

Editorial Services

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

 

Grants

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.
Role: PI
Award amount: $15,600

Completed Research Support

University of Pittsburgh, Department of Pathology Post-doctoral Research Training Grant (PPRTP)
Funding period: 07/2012 – 06/2013
Grant Title: Role of stem cell/reprogramming factors in transdifferentiation of hepatocytes to biliary epithelial cells.
Role: PI
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.
Role: PI
Award amount: $3,500

Media

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 newsletter.

Last Updated: 11/3/14