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					                                                  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:           (323) 442-3856

Fax:                      (323) 442-6481

E-mail:                   yhan@surgery.usc.edu

Place of Birth:            Chengdu City, China

Citizenship:               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, proMMP -
9 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 acti vation 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 e lucidate 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 trans-
differentiation 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) 442-
     Mailing 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 platelet-
derived 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*. “Co-
stimulation 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 Hea ling 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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