Yongwon Choi, PhD
Leonard Jarett Professor of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine
Contact InformationRoom 308, BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-6404
Fax: (215) 573-0888
Immunobiology and Experimental Pathology
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
Dr. Choi is studying the interaction between the immune and skeletal systems, including the testing and development of various biologics modulating these systems to provide the proof of concept in animal models whether agonists or antagonists of such molecules can be translated into potential treatment for human diseases such as arthritis or osteoporosis.
B.Sc. Department of Microbiology, Seoul National University, 1984
PhD (Biochemistry), University of Illinois College of Medicine, Chicago, IL , 1988
Research Fellow, Department of Medicine, Division of Basic Immunology, Howard Hughes Medical Institute, (Laboratory of Drs. John Kappler and Philippa Marrack), National Jewish Center for Immunology and Respiratory Medicine, Denver, CO., 1988-1992
Awards and Honors
First prize in National Research Forum in basic science (Korea), 1983
Cancer Research Institute Investigator Award, 1992
New York Community Trust Blood Disease Research Award, 1997
Ho-Am Prize in Medicine, 2006
The Lady Barbara Colyton Prize for Autoimmune Research (University of Pennsylvania School of Medicine Awards of Excellence), 2007
Memberships and Professional Organizations
Microbiota-independent ameliorative effects of antibiotics on spontaneous th2-associated pathology of the small intestine.
Han Daehee, Walsh Matthew C, Kim Kwang Soon, Hong Sung-Wook, Lee Junyoung, Yi Jaeu, Rivas Gloriany, Surh Charles D, Choi Yongwon, PloS one 10(2): e0118795, 2015, PMID:25689829
Regulator of fatty acid metabolism, acetyl CoA carboxylase 1 (ACC1), controls T cell immunity.
Lee, J.E., Walsh, M.C., Hoehn, K.L., James, D.E., Wherry, E.J., and Choi, Y., J. Immunol. 192(): 3190-3199, 2014
IL-18 synergizes with IL-7 to drive slow proliferation of naive CD8 T cells by costimulating self-peptide mediated TCR signals.
Walsh, M.C., Pearce, E.L., Cejas, P.J., Lee, J.E., Wang, L.-S., and Choi, Y., J. Immunol. 193(): , 2014
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, The Journal of clinical investigation 123(8): 3510-24, 2013, PMID:23867620
Dendritic Cell Expression of the Signaling Molecule TRAF6 Is Critical for Gut Microbiota-Dependent Immune Tolerance.
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, Immunity 38(6): 1211-22, 2013, PMID:23791643
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, Cell metabolism 17(2): 249-60, 2013, PMID:23395171
OSCAR is a collagen receptor that co-stimulates osteoclastogenesis in DAP12-deficient humans and mice.
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., J. Clin. Invest. 121(): 3505-3516 , 2011
TRAF6 inhibits Th17 differentiation and TGF-β mediated suppression of IL-2.
Cejas, P.J., Walsh, M.C., Pearce, E.L., Han, D., Harms, G.M., Artis, D., Turka, L.A., and Choi, Y., Blood 115(): 4750-4757, 2010
Choi, Y. Walsh, M.C., and Arron, J.R., Nature Medicine 15(): 144-145, 2009, PMID:19197288
Enhancing CD8 T cell memory by modulating fatty acid metabolism.
Pearce, E.L., Walsh, M.C., Cejas, P.J., Harms, G.M., Shen, H., Wang, L.-S., Jones, R.G., and Choi, Y., Nature 460(): 103-107, 2009