Yuan-Ping Han, PhD.

中文版

Professor of Biochemistry, Molecular Biology and Cell Biology


      
Contact: hanyp@scu.edu.cn or southcalyph@gmail.com 
The College of Life Sciences, Sichuan University, Chengdu, Sichuan, China, 6100065


1. Profile
   After more than two decades of study and work in the United States, Dr. Han has been recruited
   as the overseas talent program, appointed as Professor in the College of Life Sciences, 
   Sichuan University. As a formal faculty member in University of Southern California (USC), 
   his research was supported by National Institutes of Health, including two R01, a total of 
   $ 2.7 million, and other funds. His research focuses on tissue injury, repairing, fibrosis, 
   cirrhosis, and metabolic syndrome. In the liver field, his work mainly focuses on hepatic 
   stellate cells and liver cirrhosis, and fatty liver (NASH) study. In the skin field, the 
   main research is related to wound healing, ulcers, fibrosis in cellular mechanism. Recent 
   years, his interest has been shifted in part to the metabolic syndrome (MS) for its pathogenesis
   in systems biology. Based on the work of recent years, he is extending the efforts in R&D for 
   the new drugs used for prevention and therapeutic treatment of metabolic syndrome.  Research 
   methods involving molecular biology, biochemistry, tissue and cell biology, immunology, physiology 
   and pathology of human integration , transformation, and clinical application . He has published 
   over thirty articles (SCI).

2. Education
   • 1978-1982, Sichuan University, Department of Biology , majoring in biochemistry, a bachelor's degree
   • 1990-1996, Mount Sinai School of Medicine (The Mount Sinai School of Medicine, New York), majoring 
     in Biomedical Science (Biomedical Science), Ph.D., mentor , Dr. Ronald A. Kohanski
   • 1996-1999, University of Southern California Los Angeles Children's Hospital Los Angeles Children's
     Hospital / University of Southern California, as a postdoctoral fellow (1996-1999 ) , mentor, Dr. 
     Yun-Kai (Teddy) Fong

3. Employment
   • 1982-1985: the Ministry of Geology and Mineral Technology Research Institute, Research Associate
   • 1985-1989: Sichuan Antibiotic Institute, Research Associate
   • 1989-1990: SmithKline Pharmaceuticals (SKF, USA, Philadelphia), visiting scientist, engaged in drug 
     discovery 
   • 2000-2003, University of Southern California University of Southern California, Keck School of Medicine, 
     Research Associate
   • 2004-2007: University of Southern California University of Southern California, Keck School of Medicine, 
     Research Assistant Professor
   • 2007-2011: University of Southern California University of Southern California, Keck School of Medicine, 
     Assistant Professor (Tenure Track).  
     
     USC Keck School of Medicine, PIBBS doctoral mentor. 
     USC Department of Pathology.
     2011 – present: Professor, School of Life Sciences, Sichuan University , 
     2009-present: Visiting Professor, the Capital Medical University, Beijing You An Hospital 
     2012-present: Visiting Professor, Cedars-Sinai Medical Medical Center, Los Angeles.

4. Current Researches.
   4.1. Metabolic Syndrome (MS), from Mechanism to Development of new drugs.
        In recent years, we have shifted part of our focus to metabolic syndrome (also called X syndrome) 
        for the mechanism and R&D of new drugs.  Accompanying with the tremendous economic development in 
        China, the metabolic syndrome featured by high cholesterol, fatty liver, obesity, diabetes, was 
        rapidly spreading. Recent official statistics showed that China has 100 million sixty million people 
        suffering from various degrees of metabolic syndrome, creating big health and social burden in terms 
        of medical cost and retarded productivity.  In the West countries, a quarter of adults were 
        overweight or obese, the key marker of MS.  The danger is that metabolic syndrome causes diabetes, 
        cardiovascular diseases, and stroke, the main cause of death.  Metabolic syndrome mostly comes from 
        high calorie and high fat dietary.  Change lifestyle is an effective way to treat metabolic 
        syndrome.  Therapeutic treatment, by lowering cholesterol, blood pressure, and blood sugar, is the 
        main strategy.  In addition, enhancing the ectopic fat (abdominal) returning to the subcutaneous fat 
        cells is a new direction for prevention and treatment of metabolic syndrome.  In recent years, we 
        have launched a systems biology approach, aiming to uncover the mechanism and develop new methods to 
        prevent and treat metabolic syndrome.  Metabolic syndrome occurs in three phases. First, high-fat 
        diet induces changes of intestinal flora microbiota, resulting in increased blood endotoxin, which 
        triggers low-grade chronic inflammation. Second, as a result of chronic inflammation, insulin 
        resistance and glucose tolerances occur, into type-II diabetes.  As a compensation measure, high 
        blood glucose is converted into fatty acids into simple steatosis or even non-alcoholic 
        steatohepatitis (NASH). The fatty liver and abdominal fat tissues can argument inflammation and liver 
        injury, resulting in reduced HDL, and clotting mechanism impairment. Third, the ongoing diabetes, 
        high cholesterol, and clotting abnormalities, can produce cardiovascular obstruction, stroke, and 
        death. To this end, we lunched a study by systems biology approaches, from the malnutrition, change 
        in the intestinal flora, intestinal tract EMT, and abdominal fat inflammation, to the liver and 
        pancreas injury, as well as endocrine, exocrine to explain the metabolic syndrome pathogenesis. 
        Meanwhile, based on our work, we are developing new drugs for the prevention and treatment of 
        metabolic syndrome.

4.2. The Cell Biology of Tissue Injury, Repair, and Fibrosis.
        As a faculty member in the University of Southern California and as a PI, I spent a great effort to 
        address the cell biology of tissue injury, repair and fibrosis. The work was supported by two NIH R01 
        grants and other funds.  In a broad definition, “tissue injury” occurs in the situations of viral/
        microbial infection, pollution and toxicant intake, and a variety of chronic diseases, and cancer, 
        etc.  After injury, the body has two options to cope with the challenge, either regeneration, which 
        gives back the lost tissues, or repairing which often produces scars or fibrosis.  In the situation 
        of large-scale or sustained damage, the repair is a common choice. As a result of evolutionary 
        selection, tissue fibrosis is beneficial for the host, by generating "patches" for the lost tissue, 
        which is critical for survival.  However, sustained fibrosis also accompanies chronic diseases such 
        as cancer, heat disease, fatty liver et al.  Organ failure in the elderly is often the result of 
        tissue fibrosis.  It is estimated that about 50 % of deaths, including cancer and degenerative 
        diseases, are related to tissue fibrosis.  Being able to prevail of the tumor is largely due to the 
        fibrotic tissue, which provides a growth environment.  Our work has focused on hepatic stellate cells 
        and their trans-differentiation. We found that during the trans-differentiation process, multiple MMP 
        genes are irreversibly shut down or silenced.  We believe that in normal liver sinusoids, the normal 
        phenotypes of hepatic stellate cells are determined, by three-dimensional ECM, through epigenetic 
        determination.  Further, according to our findings, we believe that 3D ECM by down regulating II- 
        type HDAC, confers the MMP gene cluster (mmp loci) into an opening state at its epigenetic levels, 
        being ready for the signal transduction triggered by inflammatory factors. The consequently expressed 
        MMP can mobilize cryptic growth factors, which are essential for repairing.  Driving by the growth 
        factors, HSC undergo trans-differentiation into myofibroblasts, leading fibrous tissue.  
        Surprisingly, we found that many MMP genes in the myofibroblastic HSCs are irreversibly silenced, 
        which may explain well the ECM accumulation in fibrosis.  We found that in the process of stellate 
        cell trans-differentiation, II-type HDAC are gradually stabilized and accumulated, resulting in MMP 
        gene is suppressed.  We will continue to address the following questions. (1) How does the MMP gene 
        cluster change the epigenetic landscape in the trans-differentiation process, changing from the 
        opening state to the suppression? (2) How are II-type HDACs degraded by mesenchymal cells in 3D ECM? 
        (3) How does II- type HDAC incorporation with other nuclear factors to suppress the MMP genes in 
        fibrosis? 

4.3. The Immune Tolerance in Liver Fibrosis.
       Two equally important factors decide extend of tissue fibrosis. First, fibrosis is generated by 
       internal driving force, such as formation of myofibroblasts. Second, the persistence of fibrosis is 
       determined by the macro-environment of immune tolerance, which empts the fibrous tissue from immune 
       surveillance (escaping from immune surveillance). In a recent work, we found that dropping of natural 
       regulatory T cells (nTres) in acute liver injury due to apoptosis, grants the burst of inflammation.  
       And conversely, massive accumulation of induced Tregs (iTregs ) is related to liver fibrosis. We also 
       found a cascade of MMP9/13 dependent activation of TGF-beta in inducing iTregs for wound healing.  
       Part of this work has recently been accepted by the Journal of Molecular Cell Biology (impact factor: 
       7.3). On the other hand, in cooperation with the colleagues in the Beijing You An Hospital , we are 
       addressing the roles of II-type macrophages (alternatively activated macrophages) in the immune 
       tolerance in fibrosis.


5. Bibliography	
     Peer-Reviewed
     1. 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.

     2.   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.   

     3.   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.

     4.  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.
     
     5.  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.
     
     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, 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.                    
          
     8.   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:   27319-27327.
     
     9.  Yuan-Ping Han, Yih-Dar Nien and Warren L.Garner. “Fibrinogen inhibits fibroblast-mediated 
     contraction of collagen”. 
     Wound Repair and Regeneration. 2003 Sep;11(5):380-385.
     
     10.  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
     
     11. 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.
     
     12. Yuan-Ping Han*. “Matrix metalloproteinases, the pros and cons, in liver fibrosis”. 
     Journal of Gastroenterology & Hepatology. 2006 Oct; 21 Suppl 3:S88-91.
     
     13. Yuan-Ping Han*, Chunli Yan, Ling Zhou, Lan Qin, and Hidekazu Tsukamoto. “A Matrix 
     Metalloproteinase-9 Activation Cascade by Hepatic Stellate Cells in Trans-differentiation in the hree-
     dimensional Extracellular Matrix”. 
     Journal of Biological Chemistry.  2007 Apr 27;282(17):12928-39
      
     14.  Goldberg MT, Han YP, Yan C, Shaw MC, Garner WL. “TNF-alpha Suppresses alpha-Smooth Muscle Actin 
     Expression in Human Dermal Fibroblasts: An Implication for Abnormal Wound Healing”. 
     Journal of Investigative Dermatology. 2007 May 31;127 (11):2645-55
      
     15.	Cheng JH, She H, Han YP, Wang J, Xiong S, Asahina K, Tsukamoto H. “Wnt 
     antagonism inhibits hepatic stellate cell activation and liver fibrosis”. 
     American Journal of  Physiololy, (Gastrointest Liver Physiol) 2007, Nov 15; [Epub ahead of print] PMID: 
     18006602 
     
     16.  Yuan-Ping Han*, Chunli Yan and Warren L Garner. “Proteolytic Activation of Matrix 
     Metalloproteinase-9 in Skin Wound Healing Is Inhibited by alpha-1-Antichymotrypsin”.
     Journal of Investigative Dermatology. 2008 September; 128(9): 2334–2342.
     
     17.  Chunli Yan, Ling Zhou, and Yuan-Ping Han*. “Contribution of hepatic stellate cells and matrix 
     metalloproteinase-9 in acute liver failure”.  Liver International. 2008 May 26. [Epub ahead of print].
     
     18.  Cheng CF, Fan J, Fedesco M, Guan S, Li Y, Bandyopadhyay B, Birght AM, Yerushalmi D, Liang M, Chen, 
     Han YP, Woodley DT, Li W.  “Transforming growth factor alpha (TGFalpha)-stimulated secretion of 
     HSP90alpha: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich 
     environment during wound healing”.  
     Molecular Cell Biolology. 2008 May;28(10):3344-58. Epub 2008 Mar 10, MID:18332123.
     
     19. Ling Zhou, Chunli Yan, Wei Li, Yujiro Kida, Warren L. Garner and Yuan-Ping Han*. “p21 activated 
     kinase (PAK) controls expression of MMP-9”. 
     BMC Immunology 2009, 10:15,19 March
     
     20. Roben L. Gieling, Wallace, K. and Yuan-Ping Han*, “Participation of Interleukin-1 in Liver Injury 
     induced Fibrosis”. 
     American Journal of Physiology, (Gastrointest Liver Physiol) . 2009, vol. 296,1324-31
     
     21. MJ Reiss, Yuan-Ping Han, E Garcia, YK Hong, and WL Garner “1-Antichymotrypsin activity correlates 
     with and may modulate matrix metalloproteinase-9 in human acute wounds ”. 
     Wound Healing and Regeneration, 2009, Published Online: May 20 2009, p 418-426
     
     22.  Shengwen Calvin Li, Yuan-Ping Han, Brent A. Dethlefs and William Gunter Loudon “Therapeutic Window 
     of Stem Cell Potential for Targeting Pediatric Malignant Brain Tumor: An Opportunity for Stem Cell 
     Therapy”. 
     Stem Cell Review and Reports, 2009, vol.5, issue 4, p446
     
     23. MJ Reiss, Yuan-Ping Han, E Garcia, YK Hong, and WL Garner “Excessive Amount of Matrix 
     Metalloproteinase-9 Delays Wound Healing in a Murine Wound Model”. 
     Surgery, 2010, February, Volume 147, Issue 2, Pages 295-302
     
     24. Keigo Machida, Hidekazu Tsukamoto, Jian-Chang Liu, Yuan-Ping Han, Sugantha Govindarajan, Michael 
     Lai, Shizuo Akira, James Ou, “c-Jun mediates HCV hepatocarcinogenesis through STAT3 and nitric oxide-
     dependent impairment of oxidative DNA repair”. 
     Hepatology, 2010 Aug;52(2):480-92 
     
     25. Chunli Yang, Wesley Grimm, Warren Garner, and Yuan-Ping Han*, “Tumor necrosis factor-alpha induced 
     epithelial-to-mesencymal transition in human skin fibrogenesis is mediated by bone morphogenetin 
     protein-2”. 
     American Journal of Pathology, 2010, May. 176: 2247-2258. (Cover story)
     
     26. Lan Qin and Yuan-Ping Han*. “Epigenetic Repression of Matrix Metalloproteinases in Myofibroblastic 
     Hepatic Stellate Cells through Histone Deacetylases 4,Implication in Tissue Fibrosis ”.  
     American Journal of Pathology, 2010, volume 177, Issue 4, page 1915 (Monthly Highlight)
     
     27. Xiaohui Zhou, Zanxian Xia, Qin Lan, Julie Wang, Wenru Su,Yuan-Ping Han, Huimin Fan, Zhongmin 
     Liu, William Stohl, and Song Guo Zheng. “BAFF Promotes Th17 Cells  and Aggravates Experimental 
     Autoimmune Encephalomyelitis”. 
     PloS One, 2011; 6(8): Published online 2011 August. doi:  10.1371, PMCID: PMC3163640
     
     
     28. Yujiro Kida, Zan Xian Xia, Sujun Zheng, Nick M. Mordwinkin, Stan G. Louie, Song Guo      Zheng, Min 
     Feng, Hongbo Shi, Zhongping Duan, and Yuan-Ping Han*. “Interleukin-1 as an  injury signal mobilizes 
     retinyl esters in hepatic stellate cells through down regulation of lecithin retinol acyltransferase”.  
     PLoS One, 2011. 6(11): e26644. doi:10.1371/journal.pone.0026644
     
     29. Ling Lu, Jilin Ma, Zhiyuan Li, Qin Lan, Maogen Chen, Ya Liu, Zanxian Xia, Julie Wang, Yuan-Ping Han, 
     Wei Shi, Valerie Quesniaux, Bernhard Ryffel, David Brand, Bin Li, Zhongmin Liu, Song Guo Zheng. “All-
     Trans Retinoic Acid Promotes TGF-β-Induced Tregs via Histone Modification but Not DNA Demethylation on 
     Foxp3 Gene Locus”.
     PloS One, 2011; 6(9): e24590. doi:10.1371/journal.pone.0024590. 
     
     30. Liyan Chen, Feng Ren, Haiyan Zhang, Tao Wen, Zhengfu Piao, Li Zhou, Sujun Zheng,    Jing Zhang, Yu 
     Chen, Yuanping Han, Zhongping Duan, Yingji Ma. “Inhibition of  Glycogen Synthase Kinase 3b Ameliorates D-
     GalN/LPS-Induced Liver Injury by   
     Reducing Endoplasmic Reticulum Stress-Triggered Apoptosis” 
     PLoS One, 2011. September 2012 | Volume 7 | Issue 9 | e45202
     
     31. Ling Lu, Jilin Ma, Zhiyuan Li, Qin Lan, Maogen Chen, Ya Liu, Zanxian Xia, Julie   
     Wang, Yuanping Han, Wei Shi, Valerie Quesniaux, Bernhard Ryffel, David    
     Brand, Bin Li, Zhongmin Liu, and Song Guo Zheng “All-Trans Retinoic Acid Promotes 
     TGF-β-Induced Tregs via Histone Modification but Not DNA Demethylation on Foxp3  Gene Locus”. 
     PLoS One. 2011; 6(9): e24590.Published online 2011 
     
     32. Yuan-Ping Han*, Ming Kong, Sujun Zheng, Yang Ren, Hongbo Shi, and Zhongping Duan.  
      “Vitamin D In Liver Diseases: From Mechanisms to Clinical Trials”. 
     Journal of Gastroenterology and Hepatology. 2013; 28, Suppl.1: 49–55
      
     33. Ling Lu, Min Feng, Lan Qin et al., Yuan-Ping Han*. “Induction of hepatic regulatory T cells is 
     mediated by MMP13 dependent activation of latent TGF-beta by hepatic stellate cells”.  
     Journal of Molecular Cell Biology, 2013, December Issue, in press