Penn Institute for Immunology
Perelman School of Medicine at the University of Pennsylvania
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Yongwon Choi

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Leonard Jarett Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
Room 308, BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-6404
Fax: (215) 573-0888
Education:
B.Sc.
Department of Microbiology, Seoul National University, 1984.
PhD (Biochemistry)
University of Illinois College of Medicine, Chicago, IL , 1988.
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Description of Research Expertise

Dr. Choi's is interested in the molecular analysis of the osteoimmune system. The fields of immunology and bone biology have matured such that key cellular and molecular mechanisms governing the homeostasis of the individual systems are largely understood. However, despite extensive cross-regulation between bone metabolism and the immune system, the mechanisms by which one regulates the other, and the biological implications of such interactions, are poorly understood. We believe that this lack of understanding is due in part to the challenges typically associated with crossing disciplinary boundaries that form naturally during the separate evolutions of fields like modern immunology and bone biology. It is difficult enough for scientists/physicians to keep abreast of advances in multiple fields, but even more so to develop the knowledge base, skills, and materials necessary to address important issues. Therefore, it will be critical to create an environment conducive to the study of intersystem crosstalk. Awareness of intersystem crosstalk will no doubt contribute to our understanding of how both bone and the immune system are regulated in a physiologic context, both at the molecular level and at the level of organ systems. Moreover, this endeavor will lead to better treatments for human diseases involving both systems, including various inflammatory and metabolic bone diseases, as well as tumor-induced bone lysis. Many of these pathologic processes are major targets for therapeutic intervention and are being pursued in the absence of solid scientific understanding of the molecular and cellular processes underpinning these interactions. According to the first-ever report by the U.S. Surgeon General on bone health, by 2020 one in two Americans over age 50 will be at risk for fractures from osteoporosis or low bone mass. These secondary health concerns become more prominent as people not only live longer but also expect to remain active in old age. Future preventative treatments for chronic bone-related diseases that are often associated with inflammation and that impact quality of life will require a high degree of specificity, especially if tailored for a segment of the population already suffering from, or vulnerable to, other age-related ailments. We believe these issues place osteoimmunology in a position of unique clinical significance. His recent research focuses on molecular understanding of how dendritic cells and osteoclasts differentiate, and of how T cell tolerance is maintained in vivo.

Potential rotation projections: (1) Study how TRAF6 mediates IL-1 or TLR-mediated NF-kB or MAPK activation (2) Study how TRAF6 controls T cell anergy (3) Study how osteoclast differentiation is regulated

Selected Publications

Han Daehee, Walsh Matthew C, Cejas Pedro J, Dang Nicholas N, Kim Youngmi F, Kim Jihyun, Charrier-Hisamuddin Laetitia, Chau Lillian, Zhang Qin, Bittinger Kyle, Bushman Frederic D, Turka Laurence A, Shen Hao, Reizis Boris, Defranco Anthony L, Wu Gary D, Choi Yongwon: Dendritic Cell Expression of the Signaling Molecule TRAF6 Is Critical for Gut Microbiota-Dependent Immune Tolerance. Immunity 38(6): 1211-22, Jun 2013.

Bonito Anthony J, Aloman Costica, Fiel M Isabel, Danzl Nichole M, Cha Sungwon, Weinstein Erica G, Jeong Seihwan, Choi Yongwon, Walsh Matthew C, Alexandropoulos Konstantina: Medullary thymic epithelial cell depletion leads to autoimmune hepatitis. The Journal of clinical investigation 123(8): 3510-24, Aug 2013.

Kim Hyunsoo, Kim Taesoo, Jeong Byung-Chul, Cho Il-Taeg, Han Daehee, Takegahara Noriko, Negishi-Koga Takako, Takayanagi Hiroshi, Lee Jae Hee, Sul Jai-Yoon, Prasad Vikram, Lee Seoung Hoon, Choi Yongwon: Tmem64 modulates calcium signaling during RANKL-mediated osteoclast differentiation. Cell metabolism 17(2): 249-60, Feb 2013.

Barrow, A.D., Raynal, N., Andersen, T.N., Slatter, D.A., Bihan, D., Pugh, N., Cella, M., Kim, T.S., Rho, J.R., Negishi-Koga, T., Delaisse, J.-M., Takayanagi, H., Lorenzo, J., Colonna, M., *Farndale, R.W., *Choi, Y. and *Trowsdale, J. : OSCAR is a collagen receptor that co-stimulates osteoclastogenesis in DAP12-deficient humans and mice. J. Clin. Invest. 121: 3505-3516 2011.

Cejas, P.J., Walsh, M.C., Pearce, E.L., Han, D., Harms, G.M., Artis, D., Turka, L.A., and Choi, Y. : TRAF6 inhibits Th17 differentiation and TGF-β mediated suppression of IL-2. Blood 115: 4750-4757, 2010.

Pearce, E.L., Walsh, M.C., Cejas, P.J., Harms, G.M., Shen, H., Wang, L.-S., Jones, R.G., and Choi, Y. : Enhancing CD8 T cell memory by modulating fatty acid metabolism. Nature 460: 103-107, 2009.

King, C.G., Buckler, J.L., Kobayashi, T., Hannah, J.R., Bassett, G., Kim, T., Hannah, J.R., Pearce, E.L., Kim, G.G., Turka, L.A., and Choi, Y. : Cutting Edge: Requirement for TRAF6 in the induction of T cell anergy. J. Immunol. 180: 34-38, 2008.

Hamazaki, Y., Fujita, H., Kobayashi, T., Choi, Y., Scott, H.S., Matsumoto, M., and Minato, N. : Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin. Nat. Immunol. 8: 304-311, 2007.

King, C.G., Kobayashi, T., Kim, T., Yoon, K., Kim, G.K., Chiffoleau, E., Hickman, S.P., Walsh, P.T., Turka, L.A., and Choi, Y. : TRAF6 is a T cell intrinsic negative regulator required for the maintenance of immune homeostasis. Nature Medicine 12: 33-63, 2006.

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Last updated: 01/24/2014
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