Ph.D., Professor, Principal Investigator
Laboratory of Tumor and Stem Cell
Research Interests or Current Research Focus
Research in our laboratory has been focused on signal transduction in response to cellular environmental changes for cell differentiation and development under physiological and diseased conditions (e.g., inflammatory and transformed). We recently discovered that cytokines and growth factors trigger acetylation/methylation cascade in mammalian cells for signal transduction. Utilizing antibody array and nanometer technologies, we are uncovering novel protein posttranslational modifications for distinct signal transduction and transcription events involved in normal, inflammatory, and cancer cellular development.
Major Research Achievement
Tyrosine phosphorylation has long been considered to play a prominent role in signal transduction. STAT family members are signaling and transcription proteins activated by different transmembrane receptors of cytokines and growth factors. Our laboratory studies whether acetylation and methylation also play a critical role in signal transduction process. We are exploring different STAT family members for their differential acetylation and methylation patterns in gene regulation under both physiological and pathological conditions. The principle of yin-yang, the balance between opposing natural forces emphasized in Oriental medicine, can be epitomized as the property of signal transduction and gene regulation in cells. Acetylation and deacetylation, methylation and demethylation, such a balance creates a dynamic state that is responsive for cell differentiation, development, and homeostasis. Derangements of dynamically controlled balances between these opposite forces can seriously upset homeostasis in a cell. We are exploring how acetylation/methylation cascade triggered by cellular environmental changes for a cell develops from normal to inflammatory and to cancer type. We are interested in exploring how inflammatory signals mediated by cytokine recetors and STAT proteins transform cells; whether STAT form differential enhanceosomes during inflammation and transformation; and whether restoring the balance between acetylation/methylation and deacetylation/demethylation of STAT can restrict invasive growth and metastasis of cancer cells.
1982-1985: Medical degree, Zhejiang Chinese Medicine University/Beijing Medical University
1989: M. S. Utah State University, Biochemistry
1994: Ph. D. New York University School of Medicine, Environmental Medicine
Major Academic Appointments
1986-1989: Visiting Doctor/MS student for Utah State University and University of Southern California, California
1994-1998: Postdoctoral Fellow, Biochemistry, Mount Sinai Medical School and Pathology, Yale University Medical School
1998-2004: Assistant Professor, Pathology and Laboratory Medicine, Surgery, Brown University Medical School
2004-2011: Associate Professor, Department of Surgery, Brown University Medical School-Rhode Island Hospital
2010-present: Principal Investigator, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science & Shanghai Jiao-Tong University School of Medicine
Honors, Certificates, and Academic Society
1994-present: Member of American Association for the Advancement of Science
1996-1998: NIH Individual Postdoctoral Fellowship
1998-present: Member of American Cancer Society
1999-present: Member of American Microbiology Society
2000-present: Member of Chinese Biological Investigators Society
2001, 2002: Brown Medical School Dean’s Teaching Excellence Award
2007-present: Member of International Cytokine Society
2008: Honored Degree: Gradu Artium Magistri Ad Eundem Brown University
- Ma L, Gao JS, Guan Y, Shi X, Zhang H, Ayrapetov MK, Zhang Z, Xu L, Hyun YM, Kim M, Zhuang S, Chin YE. (2010) Acetylation modulates prolactin receptor dimerization. Proc Natl Acad Sci USA. 107, 19314-19319.
- Pang M, Kothapally J, Mao H, Tolbert E, Ponnusamy M, Chin YE, Zhuang S. (2009) Inhibition of Histone Deacetylase Activity Attenuates Renal Fibroblast Activation and Interstitial Fibrosis in Obstructive Nephropathy. Am J Physiol Renal Physiol. 297(4): F996-F1005.
- Sun Y, Chin YE, Weisiger E, Malter C, Tawara I, Toubai T, Gatza E, Mascagni P, Dinarello CA, Reddy P. (2009) Cutting edge: Negative regulation of dendritic cells through acetylation of the nonhistone protein STAT-3. J Immunol. 182, 5899-5903.
- Sun Z, Chin YE, Zhang DD. (2009) Acetylation of Nrf2 by p300/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response. Mol Cell Biol. 29, 2658-2672.
- Zhang Z, Xing J, Ma L, Gong R, Chin YE, Zhuang S. (2009) Transglutaminase-1 regulates renal epithelial cell proliferation through activation of Stat-3. J Biol Chem. 284, 3345-3353.
- Luo JM, Liu ZQ, and Chin YE. (2008) Overexpression of pulmonary surfactant protein A like molecules in inflammatory bowel disease tissues. J Central South Univ (Med Sci). 33, 979-986.
- Morin NA, Oakes PW, Hyun YM, Lee D, Chin YE, King MR, Springer TA, Shimaoka M, Tang JX, Reichner JS, Kim M. (2008) Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration. J Exp Med. 205, 195-205.
- Xu C, Xie J, Kohler N, Edward G, Walsh EG, Chin YE, and Sun S. (2008) Monodisperse magnetite (Fe3O4) nanoparticles coupled with nuclear localization signal (NLS) peptide for cell nuclear targeting. Chem Asian J. 3, 548-552.
- Xu C, Xie J, Ho D, Wang C, Kohler N, Walsh EG, Morgan JR, Chin YE, and Sun S.(2008) Au-Fe3O4 dumbbell nanoparticles as dual functional probes. Angew Chem Int Ed Engl. 47, 173-176.
- Si J, Fu X, Behar J, Wands J, Beer DG, Lambeth D, Chin YE, and Cao W. (2008) STAT5 mediates platelet-activating factor (PAF)-induced NADPH oxidase NOX5- S expression in Barrett’s esophageal adenocarcinoma cells. Am J Physiol Gastrointest Liver Physiol. 294, G174-183.
- Tang X, Gao JS, Guan YJ, McLane K, Ramaratnam B, and Chin YE. (2007) Acetylation-dependent signal transduction for type I interferon receptor. Cell. 131, 93-105.
- Darnowski J, Cousens LP, Guan YJ, Chatterjee D, Goulette FA, and Chin YE. (2006) STAT3 protein demolition by caspases: cellular and functional analysis. J Biol Chem. 281, 17707-17717.
- Chung AS, Guan YJ, Yuan ZL, Albina JE, and Chin YE. (2005) Ankyrin repeat and SOCS box 3 (ASB3) mediates ubiquitination and degradation of tumor necrosis factor receptor II. Mol Cell Biol. 25, 4716-4726.
- Yuan ZL, Guan AY, Chatterjee D, and Chin YE. (2005) STAT3 dimerization regulated by reversible acetylation of a single lysine residue within STAT3 Cterminal region. Science. 307, 269-273.
- Yuan ZL, Guan AY, Wang L, Wei W, Kane AB, and Chin YE. (2004) A central role of Threonine-p+1loop residue in RTK for constitutive STAT3 phosphorylation in metastastic cancer cells. Mol Cell Biol. 24, 9390-9400.
- Ivanov SS, Chung AS, Yuan ZL, Guan AY, Sachs KV, Reichner J, and Chin YE. (2004) Antibodies immobilized as arrays to profile protein post-translational modifications in mammalian cells. Mol Cell Proteomics. 3, 705-714.
- Gao Q, Hua J, Kumuri R, Headd JJ, Fu XY, and Chin YE. (2004) Identification of STAT’s linker-SH2 domain as the SH2 domain origin using two dimensional structural analysis. Mol Cell Proteomics. 3, 510-521.
- Kim S., Koga T., Isobe M., Kern BE, Yokochi T, Chin YE, Karsenty G, Taniguchi T, and Takayanagi H. (2003) Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. Genes Dev. 17, 1979-1991.
- Wu T, Hong KY, Wang XD, Ling ML, Dragoi AM, Chung AS, Campbell A, Feng GS, and Chin YE. (2002) SHP-2 is a dual-specificity phosphatase to dephosphorylate Stat1 at both tyrosine and serine residues in nuclei. J Biol Chem. 277, 47572-47580.
- Xia L, Wang L, Chung AS, Ivanov SS, Ling MY, Dragoi AM, Platt A., Gilmer TM, Fu XY, and Chin YE. (2002) Identification of both the positive and negative motifs for STAT activation within EGFR cytoplasmic domain. J Biol Chem. 277, 30716-30723.
- Wang YJ, Wu TR, Cai SY, Welt T, and Chin YE. (2000) Stat1 as a component of TNF alpha receptor 1-TRADD signaling complex to inhibit NF-κB activation. Mol Cell Biol. 20, 4505-4512.
- Liu XD, Quinn AM, Chin YE, and Fu XY. (1999) STAT genes discovered in C.Elegans. Science. 285, 167-168.
- Welte T, Leitenberg D, Dittel BN, Chin YE, Bothwell AL, Janeway CA Jr., and Fu XY. (1999) STAT5 activation is essential for TCR regulation of gene expression in T cells. Science. 283, 222-225.
- Iwamoto Y, Chin YE, Peng XB, and Fu XY. (1998) Identification and characterization of an EGF receptor associated STAT inhibitor. J Biol Chem. 273,18198-18204.
- Jiang T, Chin YE, and Tong T. (1998) Screening tyrosine kinase inhibitors for selectively inhibition of EGFR in breast cancer cell lines. Chin J Biochem Mol Biol. 14, 314-317.
- Chin YE, Kitagawa M, Kuida K, Flavell RA, and Fu XY. (1997) Activation of STAT signaling pathway can cause expression of Caspase 1 and apoptosis. Mol Cell Biol. 17, 5328-5337.
- Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto Y, and Fu XY. (1996) Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21WAF1/CIP1 mediated by STAT1. Science. 272, 719-722.
- Chin YE, Snow ET, and Christie NT. (1994) The stimulatory effects of nickel chloride on DNA replication in HeLa cells and E. coli. Carcinogenesis. 15, 1013-1016.
- Chin YE, Snow ET, Cohen MD, and Christie NT. (1994) The effects of divalent nickel (Ni2+) on DNA replication in vitro by DNA polymerase α. Cancer Res. 54,2337-2341.
- Chin YE, Snow ET, and Christie NT. (1994) A single stranded DNA binding protein isolated from HeLa cells facilitates Ni2+ activation of DNA polymerases in vitro. Biochemistry. 33, 15141-15148.
Invited reviews, comments and book chapters
1. Chung AR, and Chin YE. (2009) Differential analysis of protein posttranslational modifications in mammalian cells with antibody array. In The Bioanalytical Discovery of Post Translational Modifications. Lill J, Sandoval VN, and Pham VC eds. (Research Sign Post Publishers). pp 89-102.
2. Chung AR, and Chin YE. (2009) Antibody array platform to monitor protein tyrosine phosphorylation in mammalian cells. In Phosphoproteome. de Graauw M. ed.(Humana Press). Methods Mol Biol. 527, 247-255.
3. Chatterjee D, Sabo E, Resnick, MB, Yeung KC, and Chin YE. (2007) The RKIP and STAT3 axis in cancer chemotherapy: opposites attract. In Sensitization of Cancer Cells for Chemo/immuno/Radio-therapy. Bonavida B. ed. (Humana Press) pp 159-174.
4. Chin YE, and Fu XY. (1998) Transcription factors and apoptosis. In Apoptosis Genes. Wilson JW, Booth C, and Potten CS. eds. (Kluwer Academic Publishers) pp 119-142.
1. Methods and compositions for stimulating apoptosis and cell death or for inhibiting cell growth and cell attachment, US patent # 20030105057, 1998.
2. Antibody array method to detect proteins, US patent # 6197599, 1998.