Reza Zarnegar, PhD

Dr. Reza Zarnegar is a Professor in the Division of Experimental Pathology in the Department of Pathology at the University of Pittsburgh.

Dr. Zarnegar’s laboratory is focused on determining the physiological and pathological role of the HGF/Met axis in normal tissue homeostasis and disease processes. Dr. Zarnegar discovered and characterized Hepatocyte Growth Factor (HGF) also known as Hepatopoietin-A in the 1980’s when he was a junior faculty member at Duke University working with Dr. George Michalopoulos. Since then, Dr. Zarnegar has devoted his attention to dissecting the molecular mechanisms involved in the regulation of hepatocyte growth, liver homeostasis, and carcinogenesis with emphasis on the role of HGF and its receptor tyrosine kinase Met. His studies have led to the discovery of novel anti-apoptotic properties of Met and more recently the discovery of somatic and germline HGF gene mutation in human cancer such as breast and colon carcinomas. His lab also recently discovered that HGF-Met system is engaged in a direct cross-talk with the insulin receptor in hepatocytes and that this cross-talk has functional importance to hepatic glucose and fat metabolism. In seminal work has found that HGF-MET malfunction in the liver contributes to NAFLD and NASH.

A list of Dr. Zarnegar’s selected publications include:

  1. Ma, J., Tan, X., Kown, Y., Delgado, E.R., Zarnegar, A., DeFrances, M. C., and Zarnegar, R. A novel       humanized model of NASH and its treatment with MET4 a potent agonist of MET. (2022), Cell Mol Gastroenterol Hepatol 2022;13:565-582.
  2. Ma J, DeFrances MC, Zou C, Johnson C, Ferrell R, Zarnegar R, Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer. J Clin Invest 2009;119: 478-91. PMID: 19188684
  3. Zou C, Ma J, Wang X, Guo L, Zhu Z, Stoops J, Eaker AE, Johnson CJ, Strom S, Michalopoulos GK, DeFrances MC, Zarnegar R, Lack of Fas antagonism by Met in human fatty liver disease. Nature Medicine 2007;13: 1078-85. PMID: 17704785
  4. Fafalios A, Ma J, Tan X, Stoops J, Luo J, DeFrances MC, Zarnegar R. A hepatocyte growth factor receptor (Met)−insulin receptor hybrid governs hepatic glucose metabolism. Nature Medicine Published online: 13 November 2011 | doi:10.1038/nm.2531 17, 1577–1584 (2011)
  5. Ma J, Zou C, Guo L, Seneviratne DS, Tan X, Kwon YK, An J, Bowser R, DeFrances MC, Zarnegar R. Novel death defying domain in Met entraps the active site of caspase-3 and blocks apoptosis in hepatocytes. This article is featured on the front-page cover. 2014 May; 59(5):2010-21. PMID: 24122846 [PubMed – indexed for MEDLINE].
  6. Seneviratne D, Ma J, Tan X, Kwon YK, Muhammad E, Melhem M, DeFrances MC, Zarnegar R. Genomic Instability Causes HGF Gene Activation in Colon Cancer Cells, Promoting Their Resistance to Necroptosis. Gastroenterology, 2015 Jan;148(1):181-191.e17. doi: 10.1053/j.gastro.2014.09.019. Epub 2014 Sep 20.2014 Sep 19. [Epub ahead of print] PMID: 25244939 [PubMed – as supplied by publisher].

View a list of Dr. Zarnegar’s publications here.