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Penn Center for AIDS Research

Youhai H. Chen

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Professor of Pathology and Laboratory Medicine
Member, Institute for Human Gene Therapy
Member, Cancer Center
Member, Center for Molecular Studies in Digestive and Liver Diseases
Member, Institute of Neurological Science
Member, Penn Center for Musculoskeletal Disorders
Member, Penn Genomics Institute
Member, Institute for Diabetes, Obesity and Metabolism
Member, Clinical Immunology Center
Member, Curriculum Committee, Gene Therapy Graduate Program, CAMB, University of Pennsylvania
Member, Executive Committee, Gene Therapy Graduate Program, CAMB, University of Pennsylvania
Department: Pathology and Laboratory Medicine

Contact information
University 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
Graduate Group Affiliations
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.
Post-Graduate 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.
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Description of 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; Car-T 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 apoptosis-inducing genes such as DR5, Dr. Chen and colleagues are exploring the potential of Car-T and 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

Selected Publications

Carmody, R. J., Q. Ruan, S. Palmer, B. Hilliard, Y. H. Chen: Negative regulation of Toll-like receptor signaling by NF-kB p50 ubiquitination blockade. Science 317(5838): 675-678, 2007.

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: TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell 133: 415-426, 2008.

Ruan, Q., V. Kameswaran, Y. Tone, L. Li, H-C. Liou, M.I. Greene, M. Tone, Y.H. Chen: Development Of Foxp3+ Regulatory T Cells Is Driven By The c-Rel Enhanceosome. Immunity 31: 932-940, 2009.

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: Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nature Immunology 11: 141-147, 2010.

Li Li, Ruan Qingguo, Hilliard Brendan, Devirgiliis Jennifer, Karin Michael, Chen Youhai H: Transcriptional regulation of the Th17 immune response by IKK(alpha). The Journal of Experimental Medicine 208(4): 787-96, Apr 2011.

Ruan Qingguo, Wang Ting, Kameswaran Vasumathi, Wei Qin, Johnson Derek S, Matschinsky Franz, Shi Weiyun, Chen Youhai H: The microRNA-21-PDCD4 axis prevents type 1 diabetes by blocking pancreatic beta cell death. Proceedings of the National Academy of Sciences USA 108(29): 12030-12035, Jul 2011.

Ruan Qingguo, Kameswaran Vasumathi, Zhang Yan, Zheng Shijun, Sun Jing, Wang Junmei, Devirgiliis Jennifer, Liou Hsiou-Chi, Beg Amer A, Chen Youhai H: The Th17 immune response is controlled by the Rel-ROR{gamma}-ROR{gamma}T transcriptional axis. The Journal of Experimental Medicine 208: 2321-33, Oct 2011.

Gus-Brautbar Yael, Johnson Derek, Zhang Li, Sun Honghong, Wang Peng, Zhang Shirley, Zhang Lining, Chen Youhai H: The Anti-inflammatory TIPE2 Is an Inhibitor of the Oncogenic Ras. Molecular Cell 9(45): 610-8, Feb 2012.

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: TIPE3 is the transfer protein of lipid second messengers that promote cancer. Cancer Cell 26(4): 465-78, 2014.

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: Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2. Nature Immunology 18(12): 1353-1360, 2017.

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Last updated: 11/26/2017
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