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Hong Sun |
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| Associate Professor of Genetics |
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* B.M. Beijing Medical College, Beijing, 1982
* Ph.D. Harvard University, 1991
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| Research Interests: | |
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Molecular mechanisms of cancer and aging
Signal transduction
Tumor suppressors
Aging in C. elegans
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| General Research Interests: | |
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| We are interested in the molecular mechanisms that link cell signaling processes to cell cycle progression,
apoptosis and senescence. More specifically, we have been studying how perturbation of pathways regulated
by the PTEN tumor suppressor leads to cancer and aging.
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| Honors: | |
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* Pew Scholar in the Biomedical Sciences 1996-2000
* American Cancer Society Research Scholar 2003-2007
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| Current Research: | |
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| PTEN is an important tumor suppressor and mutations of its encoding gene is found in a variety of human cancers and
cancer predisposition syndromes. At molecular level, PTEN functions as a phosphatase for the
phosphatidylinositol-3,4,5-trisphosphate (PIP3), a product of PI 3-kinase. Using both human tumor cells and mouse embryonic
stem cells that are genetically deleted for the PTEN gene, we have demonstrated that PTEN and PI 3-kinase play important
roles in control of G1 to S phase cell cycle progression. We have identified several critical targets in this process
that include the cell cycle regulators p27KIP1, SKP2 and cyclin D1. p27KIP1, SKP2 and cyclin D1 are themselves known to
be intimately involved in human cancers. We have also found that the serine/threonine kinase Akt and the small GTPase
Rac1, signaling molecules downstream of the PI 3-kinase pathway, each plays a distinctive role in regulation of cell
cycle progression. We have also identified several novel genes that potentially involved in the PTEN and PI 3-kinase
regulated pathway. Through these studies, we hope to better understand how PTEN functions as a tumor suppressor in mammals.
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| In parallel to our studies of PTEN in mammalian systems, we have made use of the powerful C. elegans
genetic model to elucidate the signaling pathway regulated by PTEN. Our previous studies have demonstrated
that the C. elegans PTEN homolog, DAF-18, function as a negative regulator for an insulin-like signaling
pathway. We have found that daf-18 mutant animals have a lifespan 50% shorter than that of the wild-type animals.
We have since taken a genetic approach to identify new genes involved in regulation of animal lifespan. We
have isolated several mutants that have extended lifespan. Preliminary characterization of some of these mutants
suggests that they may define novel components in the insulin-like signaling pathway. We are in the process of
further mapping these mutations and cloning the corresponding genes.
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| With the combined biochemical and genetic approaches, we plan to further dissect the PTEN-regulated pathways
and to understand the molecular mechanisms of cancer and aging.
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| Representative Publications: | |
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| Li, D-M. and Sun, H. (1997) TEP1, encoded by a candidate tumor suppressor locus, is a novel protein
tyrosine phosphatase regulated by TGF?. Cancer Research, 57, 2124-2129.
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| Li, D-M. and Sun, H. (1998) PTEN/MMAC1/TEP1 suppresses tumorigenecity and blocks cell cycle progression in human
glioblastoma cells. Proc. Natl. Acad. Sci. USA 95, 15406-15411.
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| Sun, H., Lesche, R., Li, D-M., Liliental, J., Zhang, H., Gao, J., Gavrilova, N., Mueller, B., Liu, X. and Wu, H. (1999) PTEN modulates
cell cycle progression and cell survival by regulating PIP3 and Akt/PKB signaling pathway. Proc. Natl. Acad. Sci. USA 96, 6199-6204.
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| Mihaylova, V.T., Borland, C., Stern, M.J., and Sun, H. (1999). The PTEN tumor suppressor homolog in C. elegans regulates longevity
and dauer formation in an insulin-receptor like signaling pathway. Proc. Natl. Acad. Sci. USA 96:7424-7432.
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| Mamillapalli, R., Gavrilova, N., Mihaylova, V.T., Tsvetkov, L.M., Wu, H., Zhang, H., and Sun, H. (2001). PTEN regulates the
ubiquitin-dependent degradation of the CDK inhibitor p27Kip1 through the ubiquitin E3 ligase SCF(Skp2). Curr. Biol. 11:263-267.
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