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Gen-Sheng Feng e-mail: gfeng@ucsd.edu |
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Molecular Signaling in Stem Cells and Metabolic Diseases
Research in Dr. Feng’s lab is centered in two major areas. One focus is on understanding coordinated regulation of multiple signaling pathways in decisions for self-renewal or differentiation in human and mouse embryonic stem (ES) cells. In particular, we want to sort out signaling events driving the initial differentiation program in human and mouse ES cells, with the focus on elucidating the links between cytoplasmic signaling pathways and epigenetic control elements. We are also very interested in deciphering the common and distinct signaling routes in hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs), using cell type-specific gene knockout mouse models created in the lab, with the ultimate goal of identifying novel target for elimination of LSCs.
The second focus is on dissecting the molecular signaling mechanisms underlying metabolic disorders such as obesity and diabetes. Recent results obtained by this lab lead to fresh views on modulation of leptin signaling by tyrosine phosphatase Shp2 in the hypothalamus for energy balance, and negative regulation of hepatic insulin signals by Gab1 adaptor protein for glucose homeostasis. Current efforts are devoted to understanding the mechanisms of “leptin signaling and leptin resistance” and of pancreatic beta-cell regeneration, using combined genetic and biochemical approaches. The long-term goal of this work is to identify novel pharmaceutical targets for treatment of obesity/diabetes, the disease of the 21st century.
Feng GS, CC Hui and T Pawson. SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine kinases. Science 259: 1607, 1993.
Zhang EE, E Chapeau, K Hagihara and GS Feng. Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism. Proc. Natl. Acad. Sci. USA 101, 16064, 2004.
Bard-Chapeau E, AL Hevener, S Long, EE Zhang, JM Olefsky and GS Feng. Deletion of Gab1 in the liver leads to enhanced glucose tolerance and improved hepatic insulin action. Nature Medicine 11, 567-571, 2005.
An, H., W. Zhao, J. Hou, Y. Zhang, Y. Xie, H. Xu, C. Qian, T. Feng, J. Zhou, S. Liu, Y. Yu, J. Wang, G.S. Feng and X.T. Cao. SHP-2 negatively regulates TLR4/TLR3-mediated type I interferon production in macrophages by inhibiting TRIF- and TBK1-dependent signals. Immunity 25, 919-928, 2006.
Ke, Y., D. Wu, F. Princen, T. Nguyen, Y. Pang, J. Lesperance,W. J. Muller, R.G. Oshima, and G.S. Feng. Role of Gab2 in mammary tumorigenesis and metastasis. Oncogene 26, 4951-4960, 2007.
Chan, R.J. and G.S. Feng. PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase (Invited review). Blood 109, 862-867, 2007.
Ke, K., E.E. Zhang, K. Hagihara, D. Wu, Y.H. Pang, R. Klein, T. Curran, B. Ranscht, and G.S. Feng. Deletion of Shp2 in the brain leads to defective proliferation and differentiation in neural stem cells and early postnatal lethality. Mol. Cell. Biol. 27, 6706-6717, 2007.
Pan, Y., C. Carbe, A. Powers, J. D. Esko, K. Grobe, G.S. Feng, and X. Zhang. Bud specific modification of heparan sulfate regulates Shp2 dependent FGF signaling during lacrimal gland induction. Development 135, 301-310, 2008.
Wu, D., Y. Pang, Y. Ke, Z. He, L. Tautz, T. Mustelin, and G.S. Feng. A Conserved Mechanism for Control of Human and Mouse Embryonic Stem Cell Pluripotency by Shp2. PLoS ONE, 4(3): e4914, 2009.
Princen, F., E. Bard, F. Sheikh, S.S. Zhang, J. Wang, W. Zago, D. Wu, R. D. Trelles, B. Bailly-Maitre, J. C. Reed, M. Mercola, G. Tong, J. Chen, and G.S. Feng. Selective deletion of tyrosine phosphatase Shp2 in muscle leads to cardiomyopathy, insulin resistance and premature death. Mol. Cell. Biol. 29, 378-388, 2009.
Zhang, SS, E. Hao, J. Yu, W. Liu, J. Wang, F. Levine, and G.S. Feng. Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic beta-cells. Proc. Natl. Acad. Sci. USA 106, 7531-7536, 2009.
Gen-Sheng Feng is a new faculty member in the Section of Molecular Biology at U.C. San Diego. His appointment began March 1, 2009.
