Han CV, January, 2006
Curriculum Vitae
Yuan-Ping Han, Ph.D. A. Personal Information Business Address: 1450 San Pablo Street, Suite 2000 Los Angeles, CA 90033 Business Phone: Fax: E-mail: Place of Birth: Citizenship: (323) 442-3856 (323) 442-6481 yhan@surgery.usc.edu Chengdu City, China U.S.A.
B. Education Undergraduate Education B.S. Biochemistry Sichuan University, Chengdu City, Sichuan Province, China, 1978-1982 Graduate School Ph.D. Program of Biomedical Science The Mount Sinai School of Medicine New York, NY, Ph.D. 1990-1996 C. Professional Appointment Primary appointment: Assistant Professor of Surgery Department of Surgery University of Southern California 2002-present Active joint appointments: Assistant Professor of Pathology Department of Pathology University of Southern California 2004-present
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Han CV, January, 2006 Associate Member The Norris Cancer Center University of Southern California, 2003-present Member The Research Center of Alcoholic and Pancreatic Diseases University of Southern California 2004-present Previous appointments: Research Associate, Department of Surgery University of Southern California 1999-2002 Postdoctoral Fellow Children’s Hospital Los Angeles/USC 1996-1999 Visiting scientist SmithKline Beecham Pharmaceuticals King of Prussian, PA 1982-1989 D. Professional activities: Membership: Member of American Society for Cell Biology Member of ASBMB Wound Healing Society Fellowship: Visiting scientist, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 1989-1990 Post-doctoral training fellowship from NIH, Children's Hospital Los Angeles, 1996-1999 Honors and Awards: Research Recognition Award, 2001 The Wound Healing Foundation 3M Health Care The Wound Healing Society Committees:
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Han CV, January, 2006 Member, Award Committee, the Wound Healing Society, 2004, 2005 Co-organizer, the Southern California Wound Healing Symposium, 2002, 2003, 2004 Reviewer: Journal of the National Cancer Institute Wound Repair and Regeneration Journal of Biological Chemistry E. Research Support Active Grants: Principal Investigator: RO1, AR051558-01, NIAMS $1,111,110 7/1/2004 – 6/30/2009 “ACT, a pathophysiological inhibitor of MMP-9 Activation”. We identified alpha-ACT, an acute phase factor produced by liver in response to injury, as a specific inhibitor controlling maturation of proMMP-9. Not expressed in most of normal tissues, MMP-9 is massively expressed in many degenerative diseases such as chronic wound and tumor metastasis. In early phase of injury and onset of many diseases, proMMP9 is expressed but retained in latent form. Conversion of proMMP-9 has been widely observed in inflammatory diseases such as chronic wounds and cancer metastasis. We hypothesized that activation of proMMP-9 is tightly controlled by this serine proteinase inhibitor and destruction of the inhibitor may lead activation of MMP-9 in these diseases. Principal Investigator: RO1, DK069418-01, NIDDK $1,529,836 9/1/2004-8/30/2009 “Hepatic Stellate Cell Derived MMP9 in Liver Fibrogenesis”. The major goal of this grant is to elucidate the mechanism of fibrogenic activation of hepatic stellate cells, an essential process in liver fibrogenesis. Specifically, we will address the role of IL-1 induced vigorous ECM remodeling in activation of hepatic stellate cells. We will clarify the intracellular signals of the co-stimulation by IL-1 and collagen leading MMP-9 expression, activation and trans-differentiation of the hepatic stellate cells. We will identify the putative hepatic stellate cell produced proMMP-9 activator. And finally, we will define the role of IL-1 and its regulation of MMP-9 in liver fibrogenesis. Principal Investigator: Pilot Project Grant, NIAAA (the Research Center of Alcoholic and Pancreatic Diseases, USC) $64,000 12/30/2002 – 12/31/2004 “Cytokine regulation of MMPs and TIMPs by alcoholic liver”. The aims of this pilot project are to explore the roles of MMPs in hepatic stellate cell activation (trans-differentiation) and the inflammation mediated regulation of MMPs. Principal Investigator: Robert E. and May R. Wright Foundation (II) $50,000 6/30/2004 – 6/30/2006 “Purification of the hepatic stellate cell produced proMMP-9 activator”
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Han CV, January, 2006 We recently demonstrated that IL-1a induced MMP-9 has an essential role in transdifferentiation of hepatic stellate cells. However, an outstanding question is that how proMMP-9 is converted into active form by hepatic stellate cells. This grant will support us to identify this activator through protein biochemical and genomic approaches. Finished grants: Principal Investigator: Robert E. and May R. Wright Foundation (I) $50,000 7/1/2002 – 6/30/04 “Identification of the Cellular Factors Controlling MMP-9 Activation in Human Skin and Implication in Cancer Metastasis”. The aim of this project is to purify the putative proMMP-9 activator from human skin. Through the original work we have 1) defined the cytokine regulation of proMMP-9 activation by human skin, 2) established a protocol to extract the activator and 3) characterized the putative activator as a tissue bound chymotrypsin-like proteinase. Principal Investigator: The Plastic Surgery Education Foundation $5,000 2000-2001 “The cellular factors promote MMP-9 activation in chronic wound". The aim of this grant is to understand the cytokine mediated induction of proMMP-9 expression by dermal fibroblasts and keratinocytes. The signal transduction leading expression MMP is the key emphasis.
F. Research Experience Current and long term research interest: The long term goal of this lab is to elucidate the molecular biology of inflammation mediated ECM degradation in the pathogenesis of inflammation induced diseases including wound healing, fibrosis, and cancer metastasis. At molecular level we are interested to understand how ECM, cytokine and matrix degradation enzymes as well as their inhibitors determine the cell fate, differentiation, apoptosis and cell cycle in 3 dimensional ECM. Three ongoing research projects in this laboratory are: 1. Trans-differentiation of hepatic stellate cells in liver fibrosis. The goal of this project is to address how the hepatic stellate cells attain at quiescent phenotype in the basement ECM and how the collective effect of IL-1 and collagen promotes the trans-differentiation of the cells grown in 3D ECM. Further, we want to know how MMP-9 participates in the trans-differentiation of the stellate cells. A systematic approach by combination of both in vitro 3D cultures of stellate cells and in vivo animal model with gain/loss of function has been used to address these questions. 2. Mechanism of MMP-9 activation in degenerative diseases: The goal of this project is to identification the proMMP-9 converting enzyme(s). To approach the
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Han CV, January, 2006 goal we have applied protein biochemistry, proteomic and genomics. We believe that identification of the proMMP-9 activator holds the promise to further understand the molecular basis of cancer metastasis, liver fibrosis and wound healing. 3. Acute phase factor mediated inhibition of MMP-9. The goal of this project is to study the injury mediated regulation of alpha-ACT expression and the biochemical mechanism of its inhibition of the proMMP-9 activator. An integrated approach by combination of molecular biology and protein biochemistry and animal model has been applied. G. Teaching Path575, “the Frontiers of Pathology, cellular homeostasis.” coordinator and teaching for this graduate course in the Department of Pathology, USC. Path570, “Seminar in Pathology”, a graduate course in the Department of Pathology: PHBI 550, a graduate course in Biomedical and Biological Sciences (PIBBS), USC Invited teaching for clinical fellows in the Division of Dermatology, the Department of Medicine, University of Southern California
H. Supervision Graduate student (Ph.D., PIBBS): Lan Qin Surgical Residents in Lab Science from the Department of Surgery: Mathew Reiss (MD), Mytien Goldbery (M.D.) Medical Students: Edwin Garcia, … Post-doctoral Fellow: Roben Gieling (Ph.D. from Netherlands) Research associate: Ling Zhou (M.D.) Technicians: Chunli Yan, YihDar Nien, Michael Hughes,…
H. List of References 1. David Brenner, Professor and Chair of the Department of Medicine, Columbia University Email: dab2106@columbia.edu Tel: (212)-305-5838 Fax: (212)-305-9822 Mailing address: P H 8 Flr Rm 105J, 115th street, New York, NY 10027 2. Scott L. Friedman, Professor and Chair of the Division of Liver Diseases, the Mount Sinai School of Medicine: Email: scott.friedman@mssm.edu Tel: (212) 659-9501 Fax: (212) 849-2574
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Han CV, January, 2006 Mailing Address: One Gustave L. Levy Place, Box 1123 New York, NY 10029 3. Warren L. Garner, Associate Professor and Chief of the Burn Canter, USC+LAC, the Department of Surgery, University of Southern California Email: wgarner@surgery.usc.edu Tel: (323) 442-6477 Fax: (323) 442-6481 Mailing Address: 1450 San Pablo St, Suite 2000, Los Angeles, CA 90033 Additional references: 4. Hidekazu Tsukomoto, Professor and the Director of the Research Center of Alcoholic and Pancreatic Disease, UCLA+USC, the Department of Pathology, University of Southern California Email: htsukomoto@usc.edu Telephone: (323) 442-5107 FAX: (323) 442Mailing address: Mail Code: 9141, the Department of Pathology, The Keck School of Medicine, USC, Los Angeles, CA 90033 5. Tai-Lan Tuan, Associate Professor, Childrens Hospital Los Angeles, the Department of Surgery, the University of Southern California ttuan@chla.edu.edu Tel: 323-669-4183 Mailing address: 4650 Sunset Boulevard, Los Angeles, CA 90027
BIBLIOGRAPHY 1. Yuan-Ping Han, Downey S and Warren L.Garner Interleukin-1alpha-induced proteolytic activation of metalloproteinase-9 by human skin. Surgery. 2005 Nov;138(5):932-9. 2. Yuan-Ping Han*, Ling Zhou, Jiaohong Wang, Shigang Xiong, Warren L. Garner, Samuel W. French, Hidekazu Tsukamoto. “Essential role of matrix metalloproteinases in interleukin-1 induced myofibrobalstic activation of hepatic stellate cell in collagen”. Journal of Biological Chemistry. 2004, vol. 279, 4820-4828 3. Yuan-Ping Han, Yih-Dar Nien and Warren L.Garner. “Fibrinogen inhibits fibroblast-mediated contraction of collagen”. Wound Repair Regen. 2003 Sep;11(5):380-385. 4. Yuan-Ping Han*, Yih-Dar Nien and Warren L.Garner. “TNF-alpha mediated proteolytic activation of pro-MMP-9 in human skin is controlled by down regulation of the tissue inhibitor, TIMP-1 and mediated by tissue bound chymotrypsin-like proteinase”. Journal of Biological Chemistry. 2002, 277:
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Han CV, January, 2006 27319-27327 5. Yuan-Ping Han, Yih-Dar Nien and Warren L.Garner. “Recombinant human plateletderived growth factor and transforming growth factor-beta mediated contraction of human dermal fibroblast populated lattices is inhibited by Rho/GTPase inhibitor but not require phosphatidylinositol-3’ kinase”. Wound Repair and Regeneration. 2002, vol. 10, 169-176 6. Mei Chen, Fritz K. Costa, Christopher R. Lindvay, Yuan-Ping Han, and David T. Woodley. “The Recombinant Expression of Full-length Type VII Collagen and Characterization of Molecular Mechanisms Underlying Dystrophic Epidermolysis Bullosa”. Journal of Biological Chemistry. 2002, vol. 277: 2118-2124 7. Yuan-Ping Han, Micheal W. Hughes, Yih-Dar Nien and Warren L. Garner. “IL-8-Stimulated Expression of Urokinase-Type Plasminogen Activator in Human Skin and Human Epidermal Cells”. Journal of Surgery Research. 2002 Aug;106(2):328
8. Yuan-Ping Han, Tai-Lan Tuan, Huayang Wu, Michael Hughes, Warren L. Garner. “TGF-beta and TNF-alpha mediated induction and proteolytic activation of MMP-9 in human skin”. Journal of Biological Chemistry. 2001, vol.276 (25); 22341-22350 9. Yuan-Ping Han, Tuan TL, Wu H, Hughes M, Garner WL, “TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-kappa B mediated induction of MT1-MMP”. Journal of Cell Science 2001;114(Pt 1):131-139 10. Frankel M, Bishop SM, Ablooglu AJ, Yuan-Ping Han, Kohanski RA. “Conformational changes in the activation loop of the insulin receptor's kinase domain”. Protein Science 1999 Oct;8(10):2158-65 11. Yuan-Ping Han, Kohanski RA. “Phenylarsine oxide inhibits insulin activation of phosphatidylinositol 3'-kinase”. Biochem Biophys Res Commun 1997 Oct 9;239(1):316-21 12. Yuan-Ping Han*, Chunli Yan, Ling Zhou, Jiaohong Wang and Hidekazu Tsukamoto. “MMP-13 mediated activation of proMMP-9 in transdifferentiation of hepatic stellate cells in 3-dimensional ECM”
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Han CV, January, 2006 Journal of Cell Biology (pending) Yuan-Ping Han*, Ling Chou and Warren L. Garner. “Proteolytic activation of pro-matrix metalloproteinase-9 is inhibited by alpha 1-antichymotrypsin, an acute phase factor”. FESEB L (submitted). Ling Zhou, Chunli Yan, Wei Li and Warren L.Garner and Yuan-Ping Han*. “Costimulation of MMP-9 by TNF-alpha and TGF-b is mediated by p21 activated kinase (PAK) and stabilization of NF-kB by human dermal fibroblasts”. (preparation) Chunli Yan, Ling Zhou, Hide Tsukamoto and Yuan-Ping Han*. “Collapse of sinusoids in onset of lethal hepatitis is mediated by hepatic stellate cell produced MMP-9”. (preparation) PRESENTATION Yuan-Ping et al., The 12th Annual Conference of Wound Healing Society in Baltimore, Maryland. (2002) “MMP-9 activation in human skin”. Yuan-Ping Han et al., Society of Investigative Dermatology, Los Angeles, (2002) “Cytokine mediated proteolytic activation of pro-MMP-9”. Yuan-Ping Han, The 11th Annual Conference of Wound Healing Society in Albuquerque, New Mexico. (2001). "PDGF induced contraction of fibroblast populated collagen lattice". Yuan-Ping Han, The 10th Annual Conference of Wound Healing Society in Toronto, Canada. (2000). "TNF-a mediated MMP-2 activation in human skin and the dermal fibroblasts". Yuan-Ping Han, The first Conference of Wound Healing in Southern California, USC, Los Angeles. (2001). "TNF-a mediated MMP-9 activation in human skin". Yuan-Ping Han, The Gordon Research Conference in New London, New Hampshire. (2001). "TNF-alpha and TGF-beta mediated MMP-9 induction and activation in human skin". Yuan-Ping Han, The second Conference of Wound Healing in Southern California, USC, Los Angeles. (2002) Yuan-Ping Han et al., 2003 14th Annual Conference of Wound Healing Society Yuan-Ping Han et al., 2004 15th Annual Conference of Wound Healing Society
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