Reza Zarnegar, Professor
PhD, East Tennessee State University, 1987
Email: rezazar@pitt.edu
The main focus of Dr. Zarnegar's research is the analysis of hepatocyte growth factor (HGF) and HGF receptor (a protooncogene) function and their genetic regulation at the molecular level in vivo using transgenic mouse models. Emphasis is placed on unraveling the role of HGF and HGFR in normal and neoplastic tissue growth. HGF is a polypetide growth factor essential for growth of various normal tissues. It may also play a role in neoplastic transformation and metastasis. To understand the role of HGF in tumor promotion and progression, Zarnegar's laboratory has developed transgenic mice that overexpress an HGF transgene in the liver. These animals spontaneously develop hepatocellular carcinoma and are substan-tially sensitive to chemical carcinogens. In addition to being a model to analyze the molecular mechanisms of carcinogenesis, these animals also provide a system to screen potential environmental carcinogens in vivo.
Another aspect of Zarnegar's research has been the identification and char-acterization of important regulatory cis-acting elements and their cognate transcription factors which govern HGF and HGF receptor gene expression. His laboratory has cloned and characterized the promoter regions of the HGF and HGFR genes. Zarnegar's laboratory has also developed transgenic mouse models in which various lengths of the promoter region of the HGF gene direct the expression of a reporter gene, CAT. These studies have identified an injury response element that is located in the promoter region.
Recent Publication
Wang X. Zhou Y, Kim HP, Song R, Zarnegar R, Ryter SW, Choi AM. Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells. J. Biol. Chem. (2004). 279(7):5237-5243.
Zhu, Z., He, X., Johnson, C., Stoops, J., Eaker, A., Stoffer, S., Bell, A., Zarnegar, R., and DeFrances, MC. Negative regulation of PI3K by PIK3IP1, a novel p110 interacting protein. Bioch. Biophys. Res. Comm. (2007). 358: 66-72.
Zou, C., Ma, J., Wang, X, Guo, L., Zhu, Z., Stoops, J., Eaker, A.E., Johnson, C., Strom, S., Michalopoulos, G.K., DeFrances, M.C., and Zarnegar, R. Lack of Fas antagonism by Met in human fatty liver disease: The alpha chain of Met is a natural antagonist of FasL via a novel YLGA motif (2007). Nature Medicine. September issue volume 13 (9): pages 1078-1085.
Zhao, Y., DiFrancesca, D., Wang, X., Zarnegar, R., Michalopoulos, G.K., and Xiao-Min Yin. Promotion of Fas-mediated Apoptosis in Type II Cells by High Doses of Hepatocyte Growth Factor Bypasses the Mitochondrial Requirement. Journal of Cellular Physiology (2007). Nov; 213(2):556-563.
Yan P. Yu, Guoying Yu, George Tseng, Kathleen Cieply, Joel Nelson, Marie C., DeFrances, Reza Zarnegar, George K., Michalopoulos and Jian-Hua Luo. Glutathione Peroxidase 3, Deleted or Methylated In Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis (2007). Cancer Research. Sep 1; 67(17):8043-8050.
Wang, X. Defrances, M.C., Dai, Y. Bell, A., Michalopoulos G.K. and R. Zarnegar (2002). A novel mechanism of cell survival: sequestration of the death receptor Fas by direct physical association with the tyrosine kinase receptor Met. Molecular Cell 9:411-422.
Jiang, J-G, Johnson, C., and R. Zarnegar (2001). PPAR-gamma-mediated transcriptional upregulation of the HGF gene promoter via a novel composite
cis-acting element. J. Biol. Chem. 276:25049-25056.
Jiang, J-G., Gao B., and R. Zarnegar (2000). The concerted regulatory functions of the transcription factors NF1 and USF family on a composite
element in the promoter of the HGF gene. Oncogene 19:2786-2790.
Seol, D-W., Chen, Q., and R. Zarnegar (2000). Transcriptional activation of the met protooncogene by its ligand HGF is mediated through AP1. Oncogene 19:1132-1137.
