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Associate Member, St. Jude Faculty
Hongbo Chi, PhD
MS 351, Room E7052
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Phone: (901) 595-6282
FAX: (901) 595-5766
PhD - University of Rochester, Rochester, NY
Cellular Signaling in the Innate and Adaptive Immune Systems
The underlying theme of our research is to understand signaling mechanisms that control the differentiation and function of T cells, a central cell type in adaptive immunity. We have used a combination of approaches including mouse genetics, cellular immunology and biochemistry, as well as models of autoimmune and infectious diseases (multiple sclerosis, colitis and listeriosis). Within the underlying theme of our research, we have explored T cell responses from two complementary angles: the molecular pathways intrinsic to T cells, and the pathways that act in dendritic cells to cross-regulate T cell responses. For T cell-intrinsic mechanisms, we have been particularly interested in mTOR and S1P1-associated signaling and metabolic pathways that control the differentiation of regulatory and effector T cells (See Liu Nat Immunol 2009 & 2010; Yang Nat Immunol 2011; Shi J Exp Med 2011). For dendritic cell-mediated extrinsic control of T cell differentiation, we have focused on MAP kinase-related signaling pathways (see Huang Immunity 2011; Huang Nat Immunol 2012; Wang PNAS 2012). Significant insight into the physiological roles of signaling pathways could impact our understanding of fundamental mechanisms of immune regulation and manifest legitimate therapeutic opportunities.
Huang G, Wang Y, Vogel P, Kanneganti TD, Otsu K, Chi H. Signaling via the kinase p38α programs dendritic cells to drive TH17 differentiation and autoimmune inflammation. Nat Immunol 13:152-161, 2012.
Wang Y, Huang G, Vogel P, Neale G, Reizis B, Chi H. Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function. Proc Natl Acad Sci USA 2012, advance online publication.
Yang K, Neale G, Green DR, He W, Chi H. The tumor suppressor Tsc1 enforces quiescence of naïve T cells to promote immune homeostasis and function. Nat Immunol 12:888-897, 2011.
Huang G, Wang Y, Shi LZ, Kanneganti TD, Chi H. Signaling by the phosphatase MKP-1 in dendritic cells imprints distinct effector and regulatory T cell fates. Immunity 35:45-58, 2011.
Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR*, Chi H*. (* shared senior authorship). HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208:1367-1376, 2011.
Liu G, Yang K, Burns S, Shrestha S, Chi H. The S1P1-mTOR axis directs the reciprocal differentiation of TH1 and Treg cells. Nat Immunol 11:1047-1056, 2010.
Liu G, Burns S, Huang G, Boyd K, Proia, RL, Flavell RA, Chi H. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat Immunol 10:769-777, 2009.
Menon S*, Chi H*, Zhang H, Deng X, Flavell RA, Wei N. (*equal contribution) COP9 Signalosome subunit 8 (Csn8) is essential for peripheral T cell homeostasis and antigen receptor-induced cell cycle entry from quiescence. Nat Immunol 8:1236-1245, 2007.
Chi H, Barry SP, Roth RJ, Wu JJ, Jones EA, Bennett AM, Flavell RA. Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses. Proc Natl Acad Sci USA 103:2274-2279, 2006.
Wan YY*, Chi H*, Xie M, Schneider MD, Flavell RA. (*equal contribution) The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function. Nat Immunol 7:851-858, 2006.
Chi H, Flavell RA. Cutting edge: regulation of T cell trafficking and primary immune responses by sphingosine 1-phosphate receptor 1. J Immunol 174:2485-2488, 2005.
Chi H*,Sarkisian MR*, Rakic P, Flavell RA. (*equal contribution) Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube development. Proc Natl Acad Sci USA 102:3846-3851, 2005.
Chi H, Lu B, Takekawa M, Davis RJ, Flavell RA. GADD45β/GADD45γ and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNγ production in T cells. EMBO J 23:1576-1586, 2004.
Last update: February 2012