LIANG ZHOU
Ariad-Irvington Institute Fellow
Ph.D. University of California, Los Angeles. 2004
M. D. Nanjing Medical University. China. 1996
lzhou@saturn.med.nyu.edu
My thesis research in Dr. Steve SmaleÕs laboratory is to elucidate the transcriptional regulatory mechanisms for the IL-12 p40 gene. Three specific questions have been addressed. (1). What are the molecular mechanisms responsible for nucleosome remodeling at the p40 promoter? I have developed an insulator based-stable transfection assay that can recapitulate the endogenous chromatin environment at the p40 promoter. Using this novel system, individual functions of cis-acting elements at the p40 promoter in transcription and nucleosome remodeling were revealed. (2). Are any distal control regions involved in the regulation of the p40 gene? I identified a novel DNase I hypersensitivity site located about 10 kb upstream of the p40 promoter. This site is highly conserved through evolution and functions as an enhancer. Using chromatin immunoprecipitation and gel shift assays, I identified multiple transcription factors that bind this enhancer. The chromatin changes stimulated by this enhancer were characterized and the cis-acting element responsible for nucleosome remodeling at the enhancer was identified. (3). What are the molecular mechanisms underlying the inhibition of p40 expression by the anti-inflammatory cytokine IL-10? My results showed that IL-10 inhibits IL-12 p40 gene transcription in peritoneal macrophages by targeting a late event in the activation pathway.My postdoctoral projects involve studying molecular mechanisms of an orphan nuclear hormone receptor- RORgt in thymocyte differentiation and lymphoid organogenesis. Two major aims in my projects are: (i) Identifying the target genes that RORgt regulates. (ii) Identifying RORgt interacting proteins. These studies will deepen our understanding of both immune system development and regulation of host immunity against various pathogens by nuclear hormone receptors.
PublicationsZhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR. IL-6 programs T(H)-17 cell differentiation by promoting engagement of IL-21 and IL-23 pathways. Nat Immunol.(2007) Epub ahead of print
Zhou L, Nazarian AA, Xu J, Tantin D, Corcoran LM, Smale ST. An inducible enhancer required for IL-12b promoter activity in an insulated chromatin environment. Mol Cell Biol. (7):2698-712. (2007).
Sanjabi S, Williams KJ, Saccani S, Zhou L, Hoffmann A, Ghosh G, Gerondakis S, Natoli G, Smale ST. A c-Rel Subdomain responsible for enhanced DNA-binding affinity and selective gene activation Genes Dev. (18):2138-51. (2005).
Feng, H., W. Zhong, G. Punkosdy, S. Gu, L. Zhou, E. K. Seabolt, E. T. Kipreos. CUL-2 is required for the G1-to-S-phase transition and mitotic chromosome condensation in Caenorhabditis elegans. . Nature Cell Biol. 8, 486-92 (1999).
Yu, M. C., T. C. Orlando, N. R. Sturm, L. Zhou, R. M. Saito, L. M. Floeter-Winter, D. A. Campbell. Two distinct functional spliced leader RNA gene arrays in Leishmania tarentolae are found in several lizard Leishmania species. Int. J. Parasitol. 32(11), 1411-22 (2002).
Bradley, M. N.,L. Zhou, S. T. Smale. C/EBPb regulation in lipopolysaccharide-stimulated macrophages. Mol. Cell. Biol. 23(14), 4841-58 (2003).
L. Zhou, A. A. Nazarian, S. T. Smale. Interleukin-10 inhibits interleukin-12 p40 gene transcription by targeting a late event in the activation pathway. Mol. Cell. Biol. 24(6), 2385-96 (2004).
L. Zhou, A. A. Nazarian, S. T. Smale. Identification and characterization a distal enhancer at the murine interleukin-12 p40 locus. In preparation.
L. Zhou, A. A. Nazarian, S. T. Smale. Molecular mechanisms of nucleosome remodeling at the IL-12 p40 promoter. In preparation.
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