Samuel Wheeler French, M.D., Ph.D.

Work Address:
Factor 8-240K
Los Angeles, CA 90095, CA

Affiliations
Affiliations
Assistant Professor, Pathology and Laboratory Medicine, Surgical Pathology, Gastrointestinal & Liver Pathology
Member, Biochemistry, Biophysics & Structural Biology GPB Home Area, CTSI, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, Molecular Pharmacology GPB Home Area, Tumor Immunology Program at the Jonsson Comprehensive Cancer Center (JCCC) , themes
Faculty, Cellular and Molecular Pathology PhD Program
Research Interests
Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide. One of most common causes of HCC includes infection with hepatitis C virus (HCV) in association with cirrhosis. We study the impact of HCV on hepatocyte cell signaling that augments viral infection and promotes hepatocarcinogenesis. We primarily utilize a proteomic approach to identify pathways targeted by HCV. The HCV encoded NS5A and CORE proteins appear to alter cell growth and are reported to protect cells from apoptosis. We hypothesize Core and NS5A alter hepatocyte signaling pathways that promote HCV infection and lead to development of hepatocellular carcinoma. Through coimmunoprecipitation, we have recently identified NS5A in complex with heat shock proteins (HSP)s that we term the NS5A/HSP complex. Formation of the NS5A/HSP complex may significantly alter cell signaling, facilitate viral replication, and be tumorigenic. We have found that the HSP synthesis inhibitor Quercetin markedly reduces HCV infection in tissue culture and we are now initiating a phase one clinical trial to determine Quercetin’s safety and efficacy in subjection with chronic HCV infection. Identification and elucidation of novel pathways affected by HCV will allow biomarker development and non-toxic drug design to treat and prevent HCV as well as HCC.
Biography

Samuel French is a liver pathologist and scientist who has been on faculty at the UCLA Department of Pathology since 2002. Dr. French earned his B.A. in Biophysics at U.C. Berkeley and M.D. and Ph.D. in Biochemistry at the University of Pittsburgh. He completed his residency in Pathology at UCLA as well as fellowship in gastrointestinal/liver pathology. He was a postdoctoral fellow at ucla where he worked on lymphomagenesis. He is a recipien of the Boyer-Parvin Postdoctoral Recognition Award and Cure Named New Investigator Award. Dr. French is currently developing a proteomic based program to study the developoment of liver cancer from hepatitis C viral infection.

Publications

A selected list of publications:

Wang Geng, Chen Hsiao-Wen, Oktay Yavuz, Zhang Jin, Allen Eric L, Smith Geoffrey M, Fan Kelly C, Hong Jason S, French Samuel W, McCaffery J Michael, Lightowlers Robert N, Morse Herbert C, Koehler Carla M, Teitell Michael A   PNPASE regulates RNA import into mitochondria Cell, 2010; 142(3): 456-67.
Gonzalez Oscar, Fontanes Vanessa, Raychaudhuri Santanu, Loo Rachel, Loo Joseph, Arumugaswami Vaithilingaraja, Sun Ren, Dasgupta Asim, French Samuel W   The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production Hepatology (Baltimore, Md.), 2009; 50(6): 1756-64.
Koh Stephen, Bradley Robert F, French Samuel W, Farmer Douglas G, Cortina Galen   Congenital visceral myopathy with a predominantly hypertrophic pattern treated by multivisceral transplantation Human pathology, 2008; 39(6): 970-4.
Kuraishy Ali I, French Samuel W, Sherman Mara, Herling Marco, Jones Dan, Wall Randolph, Teitell Michael A   TORC2 regulates germinal center repression of the TCL1 oncoprotein to promote B cell development and inhibit transformation Proceedings of the National Academy of Sciences of the United States of America, 2007; 104(24): 10175-80.
French Samuel W, Dawson David W, Chen Hsiao-Wen, Rainey Robert N, Sievers Stuart A, Balatoni Cynthia E, Wong Larry, Troke Joshua J, Nguyen Mai T N, Koehler Carla M, Teitell Michael A   The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity Cancer letters, 2007; 248(2): 198-210.
Rainey Robert N, Glavin Jenny D, Chen Hsiao-Wen, French Samuel W, Teitell Michael A, Koehler Carla M   A new function in translocation for the mitochondrial i-AAA protease Yme1: import of polynucleotide phosphorylase into the intermembrane space Molecular and cellular biology, 2006; 26(22): 8488-97.
Chen Hsiao-Wen, Rainey Robert N, Balatoni Cynthia E, Dawson David W, Troke Joshua J, Wasiak Sylwia, Hong Jason S, McBride Heidi M, Koehler Carla M, Teitell Michael A, French Samuel W   Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis Molecular and cellular biology, 2006; 26(22): 8475-87.