PEOPLE

Youhai H. Chen, MD, PhD

Professor of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine

Contact InformationUniversity of Pennsylvania School of Medicine
Department of Pathology and Laboratory Medicine
713 Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 898-4671
Fax: (215) 573-3434

Email: yhc@pennmedicine.upenn.edu

Specialty Division

Immunobiology and Experimental Pathology

Research Expertise

Research Interests
Immunity, Inflammation, Cancer, and Gene Therapy.

Key words: Autoimmune diseases, cancer, immunity, inflammation.

Research Summary
Research Techniques: Molecular and Cellular Biology; Immunology; Genomics; Gene therapy.

I. Genes and Genomics of Autoimmune Inflammation. A major goal of Dr. Chen’s research program is to understand the molecular mechanisms of inflammatory diseases (such as multiple sclerosis and type 1 diabetes) and to find a cure for these diseases. Although the etiological factors that trigger these diseases vary, the common pathological outcome of autoimmune diseases is the destruction of self-tissues by activated lymphoid and myeloid cells through a process called autoimmune inflammation. Development of autoimmune inflammation requires coordinated expression of myriad genes that mediate the activation, migration and effector functions of inflammatory cells. These include genes that encode antigen receptors, costimulatory molecules, cytokines, chemokines, and cytotoxic enzymes. To explore the spectrum and global patterns of gene expression during autoimmune inflammation, Dr. Chen’s laboratory has performed functional genomic studies of autoimmune inflammation in the central nervous system (CNS). Inflammation in the CNS not only induced the expression of many immune-related genes, but also significantly altered the gene expression profile of neural cells. A number of unique clusters of genes were identified which represent putative immune and nervous responses in autoimmune inflammation. Using models of inflammation, Dr. Chen and colleagues are exploring the physiological and pathological roles of the following genes: the Rel/nuclear factor (NF)-kB family, microRNA-21, and Pdcd4. The following questions are being examined: 1) What are the roles of these genes in the activation, differentiation, and effector function of inflammatory cells following antigen or Toll-like receptor activation? 2) What are the roles of these genes in the death of lymphoid cells, myeloid cells, oligodendrocytes and pancreatic beta cells?

II. Inflammation, Cancer, and the TIPE Family. The connection between cancer and inflammation is widely recognized, yet the underlying molecular mechanisms are poorly understood. By genomic profiling of inflamed tissues, Dr. Chen and colleagues discovered in 2002 three members of the TIPE (TNF-alpha-induced protein 8-like) family. They have since crystallized two of them and generated mice deficient in three of them. They discovered that TIPE family plays crucial roles in both inflammation and cancer, and provides a molecular bridge between inflammation and cancer by targeting signaling molecules shared by them. Dr. Chen and colleagues are investigating the molecular mechanisms of TIPE action in immunity, inflammation, and cancer, and new TIPE-based strategies to treat inflammation and cancer.

III. Immunotherapy and Gene Therapy. Targeting Rel and TIPE genes, Dr. Chen and colleagues are exploring the potential of gene therapy approaches for the treatment of cancer and autoimmune diseases.


Potential Rotation Projects:

1. To determine the roles of NF-kB and TIPE proteins in the activation and effector function of inflammatory cells.
2. To determine the roles of NF-kB and TIPE2 in the death of lymphoid cells, myeloid cells, oligodendrocytes and pancreatic beta cells.
3. To characterize the TIPE family signaling pathways.
4. To define the roles of TIPE family in the migration of immune and cancer cells.

Lab Personnel:

Sun, Honghong, hsun2@pennmedicine.upenn.edu
Boggs, Amanda, aboggs@pennmedicine.upenn.edu
Goldsmith, Jason, goldsj@pennmedicine.upenn.edu
Li, Vivian, mingyue.li@pennmedicine.upenn.edu
Li, Xinyuan, xl@pennmedicine.upenn.edu
Zamani, Ali, zamania@pennmedicine.upenn.edu
Lin, Mei, linmei@pennmedicine.upenn.edu
Wang, Wei, wwang_fmmu@hotmail.com
Li, Ting, Tingli1@pennmedicine.upenn.edu
Katharine Cocherl, kcocherl@seas.upenn.edu
Nina Spitofsky, nspit@sas.upenn.edu
Ryan Hood, ryanhood@sas.upenn.edu
Dawn Williams, dawnw@pennmedicine.upenn.edu

Itmat Expertise

Dr. Chen's research focuses on developing new drugs for treating inflammatory diseases, including current testing of small molecule inhibitors of the nuclear factor kappa B pathway.

Graduate Groups

Cell and Molecular Biology
Immunology

Education

M.D. (Medicine), Shandong University, Shandong, China, 1986
Ph.D. (Immunology), University of Manitoba, Winnipeg, Manitoba, Canada, 1993
Post-Doc. (Immunology), Harvard University, Boston, Massachusetts, USA, 1995

Specialty Certification

Postgraduate Training

Resident/Teaching Assistant, Department of Medicine, Shandong University, Shandong, China, 1986-1987
Medical Research Council (MRC) Fellow, Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada, 1990-1993
Research Fellow, Center for Neurological Diseases, Brigham and Women's Hospital, Harvard University, Boston, MA, 1993-1995

Awards and Honors

Medical Research Council (MRC) Fellowship Award, 1990-1993
Travel Award, Canadian Society for Immunology, 1992
Medical Research Council (MRC) Scholar Award, 1994-1995
M.A. hon., Arts, University of Pennsylvania, Philadelphia, PA, 2001
Lady Barbara Colyton Prize for Autoimmune Research, 2002
Member, Henry Kunkel Society, 2008

Memberships and Professional Organizations

Canadian Society for Immunology, 1992 - 1995
New York Academy of Science, 1994 - Present
American Association for the Advancement of Science, 1994 - Present
American Association of Immunologists, 1995 - Present
American Society for Gene Therapy, 1995 - Present
Cystic Fibrosis Foundation, 1996 - 1997
Center for Scientific Reviews, National Institutes of Health, 1999 - 2000
Center for Scientific Reviews, National Institutes of Health, 1999 - 2000
Center for Scientific Reviews, National Institutes of Health, 2000 - 2001
Center for Scientific Reviews, National Institutes of Health, 2001 - 2005
Shandong University Alumni Association, 2003 - 2011
Center for Scientific Reviews, National Institutes of Health, 2004 - 2005
Michigan Diabetes Research Center, 2004 - 2005
Austrian Science Fund, Austria, 2004 - 2007
Shandong University Alumni Association, 2005 - 2014
Shandong Eye Institute, China, 2005 - Present
NINDS, National Institutes of Health, 2005 - 2006
NIAID, National Institutes of Health, 2005 - 2006
Amgen, Inc., 2006 - 2007
NIAID, National Institutes of Health, 2006 - 2007
Easton Associates, LLC, New York, 2006 - 2007
Center for Scientific Reviews, National Institutes of Health, 2006 - 2007
The Italian Association for Cancer Research, 2006 - 2010
Center for Scientific Reviews, National Institutes of Health, 2007 - 2008
NIAID, National Institutes of Health, 2007 - 2008
L.E.K. Consulting, 2007 - 2009
Health Research Board, Ireland, 2007 - 2008
NINDS, National Institutes of Health, 2007 - 2007
Cancer Research UK, UK, 2008 - 2009
Chinese Academy of Sciences, 2008 - 2009
National Multiple Sclerosis Society, 2008 - 2008
National Multiple Sclerosis Society, 2009 - 2014
Center for Scientific Review, NIH, 2009 - 2009
Center for Scientific Review, NIH, 2009 - 2009
Ministry of Science and Technology, China, 2009 - 2015
The National Institute of Dental and Craniofacial Research (NIDCR), NIH, 2010 - 2010
Center for Scientific Review, NIH, 2010 - 2010
Natural Science Foundation of China (NSFC), 2010 - Present
National Multiple Sclerosis Society, 2012 - 2015
Department of Defense, USA, 2013 - 2013
Center for Scientific Review, National Institutes of Health, 2013 - 2013
Center for Scientific Review, National Institutes of Health, 2014 - 2014
ImmuneTarget Inc., USA, 2014 - Present
Helmsley Charitable Trust , USA, 2014 - 2014
Binde Inc, 2015 - Present
Amshenn Inc., 2015 - Present
Center for Scientific Review, National Institutes of Health, 2016 - 2017
Center for Scientific Review, National Institutes of Health, USA, 2018 - Present

Web Links


Selected Publications

Negative regulation of Toll-like receptor signaling by NF-kB p50 ubiquitination blockade.

Carmody, R. J., Q. Ruan, S. Palmer, B. Hilliard, Y. H. Chen, Science 317(5838): 675-678, 2007

TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis.

Sun, H., S. Gong, R. J. Carmody, A. Hilliard, L. Li, J. Sun, L. Xu, B. Hilliard, S. Hu, H. Shen, X. Yang, Y. H. Chen, Cell 133(): 415-426, 2008, PMID:18455983

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Development Of Foxp3+ Regulatory T Cells Is Driven By The c-Rel Enhanceosome

Ruan, Q., V. Kameswaran, Y. Tone, L. Li, H-C. Liou, M.I. Greene, M. Tone, Y.H. Chen, Immunity 31(): 932-940, 2009

Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21

Sheedy, F.J., E. Palsson-McDermott, E.J. Hennessy, C. Martin, J. O’Leary, Q. Ruan, D.P Johnson, Y.H. Chen, and L.A.J. O’Neill, Nature Immunology 11(): 141-147, 2010

Transcriptional regulation of the Th17 immune response by IKK(alpha).

Li Li, Ruan Qingguo, Hilliard Brendan, Devirgiliis Jennifer, Karin Michael, Chen Youhai H, The Journal of Experimental Medicine 208(4): 787-96, 2011, PMID:21402739

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The microRNA-21-PDCD4 axis prevents type 1 diabetes by blocking pancreatic beta cell death.

Ruan Qingguo, Wang Ting, Kameswaran Vasumathi, Wei Qin, Johnson Derek S, Matschinsky Franz, Shi Weiyun, Chen Youhai H, Proceedings of the National Academy of Sciences USA 108(29): 12030-12035, 2011, PMID:21730150

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The Th17 immune response is controlled by the Rel-ROR{gamma}-ROR{gamma}T transcriptional axis.

Ruan Qingguo, Kameswaran Vasumathi, Zhang Yan, Zheng Shijun, Sun Jing, Wang Junmei, Devirgiliis Jennifer, Liou Hsiou-Chi, Beg Amer A, Chen Youhai H, The Journal of Experimental Medicine 208(): 2321-33, 2011

The Anti-inflammatory TIPE2 Is an Inhibitor of the Oncogenic Ras.

Gus-Brautbar Yael, Johnson Derek, Zhang Li, Sun Honghong, Wang Peng, Zhang Shirley, Zhang Lining, Chen Youhai H, Molecular Cell 9(45): 610-8, 2012, PMID:22326055

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TIPE3 is the transfer protein of lipid second messengers that promote cancer.

Fayngerts Svetlana A, Wu Jianping, Oxley Camilla L, Liu Xianglan, Vourekas Anastassios, Cathopoulis Terry, Wang Zhaojun, Cui Jian, Liu Suxia, Sun Honghong, Lemmon Mark A, Zhang Lining, Shi Yigong, Chen Youhai H, Cancer Cell 26(4): 465-78, 2014, PMID:25242044

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Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2.

Fayngerts Svetlana A, Wang Zhaojun, Zamani Ali, Sun Honghong, Boggs Amanda E, Porturas Thomas P, Xie Weidong, Lin Mei, Cathopoulis Terry, Goldsmith Jason R, Vourekas Anastassios, Chen Youhai H, Nature Immunology 18(12): 1353-1360, 2017, PMID:29058702

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Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response.

Chen Gang, Huang Alexander C, Zhang Wei, Zhang Gao, Wu Min, Xu Wei, Yu Zili, Yang Jiegang, Wang Beike, Sun Honghong, Xia Houfu, Man Qiwen, Zhong Wenqun, Antelo Leonardo F, Wu Bin, Xiong Xuepeng, Liu Xiaoming, Guan Lei, Li Ting, Liu Shujing, Yang Ruifeng, Lu Youtao, Dong Liyun, McGettigan Suzanne, Somasundaram Rajasekharan, Radhakrishnan Ravi, Mills Gordon, Lu Yiling, Kim Junhyong, Chen Youhai H, Dong Haidong, Zhao Yifang, Karakousis Giorgos C, Mitchell Tara C, Schuchter Lynn M, Herlyn Meenhard, Wherry E John, Xu Xiaowei, Guo Wei, Nature 560(): 382–386 , 2018, PMID:30089911

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