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Jun R. Huh
The Jane Coffin Childs Memorial Fund Fellow
Ph.D. California Institute of Technology
Jun.Huh@med.nyu.edu

The orphan nuclear hormone receptor RORgamma-t is both necessary and sufficient for generation of pathogenic T lymphocytes expressing interleukin 17 (Th17 cells). Th17 cells are closely linked with many human autoimmune diseases including multiple sclerosis, psoriasis, and rheumatoid arthritis. Using genetic loss-of-function and chemical screens, I am trying to identify genetic and small molecule modulators of RORgamma-t. This information will not only inform us as to the biology of RORgamma-t activity, but may also lead to development of therapeutic approaches to treat autoimmune diseases.

Cells comprising a multi-cellular organism possess exactly the same genetic information. Yet, the fates, or phenotypes of these cells, are distinct from each other. Moreover, once a cell commits itself to a specific lineage, it faithfully maintains this chosen identity throughout its lifetime. This commitment mechanism is called ‘epigenetic,’ because it establishes heritable patterns of gene expression without altering DNA sequences per se.

My research interest is to identify such mechanism using a well-characterized CD4 locus during cytotoxic CD8 T cell development as a model system. Previous studies in the Littman laboratory have shown that a short stretch of DNA sequences, coined as the CD4 silencer, is both sufficient and necessary to bring about CD4 gene suppression in CD8 cells. Once T cells develop into mature CD8 cells, however, CD4 locus is epigenetically suppressed regardless of the presence of CD4 silencer. I am developing genetic screening methods in order to identify a set of genes, which are essential to maintain epigenetic suppression of CD4 gene locus. Knowledge of such genes may be useful for the study of other biological systems including stem cell research and cancer development.

Selected Publications

Huh JR, Foe I, Muro I, Chen CH, Seol JH, Yoo SJ, Guo M, Park JM, and Hay BA. (2007) The Drosophila Inhibitor of Apoptosis (IAP) DIAP2 Is Dispensable for Cell Survival, Required for the Innate Immune Response to Gram-negative Bacterial Infection, and Can Be Negatively Regulated by the Reaper/Hid/Grim Family of IAP-binding Apoptosis Inducers. J. Biol. Chem., 282 (3): 2056-2068.

Hay BA, Huh JR, and Guo M. (2004) The genetics of cell death: approaches, insights and opportunities in Drosophila. Nat Rev Genet. 5(12), 911-22.

Huh JR, Guo M, and Hay BA. (2004) Compensatory proliferation induced by cell death in the Drosophila wing disc requires activity of the apical cell death caspase Dronc in a nonapoptotic role. Curr Biol. 14(14), 1262-1266.

Huh JR, Vernooy SY, Yu H, Yan N, Shi Y, Guo M, and Hay BA. (2004) Multiple apoptotic caspase cascades are required in nonapoptotic roles for Drosophila spermatid individualization. PLoS Biol. 2(1), 43-53.

Yoo SJ*, Huh JR*, Muro I, Yu H, Wang L, Wang SL, Feldman RM, Clem RJ, Muller HA, and Hay BA. (2002) Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms. Nat Cell Biol 4(6), 416-24.