X.F. Steven Zheng
University Professor

Growth control. signal transduction. cancer. chemical genetics and genomics. drug discovery

Growth is the process whereby cells accumulate mass. which determines the sizes of cells. organs and organisms. Deregulation of growth is directly linked to human diseases from cancer. aging. diabetes and a number of neurological disorders. We are interested in understanding the basic signal transduction mechanisms by which cell growth is regulated and their roles in human diseases. and ultimately developing effective therapeutics. Specifically. we research on the target of rapamycin (TOR) protein. a highly conserved phosphatidylinositol kinase-related kinase (PIKK). TOR has been shown to be a central mediator of nutrient signals to regulate eukaryotic cell growth. Not surprisingly. TOR has become an important drug target for treatment of cancer. aging. diabetes. graft rejection and several neurological disorders. On-going projects in the lab include:

(1) Study the spatial and temporal regulation of mammalian TOR (mTOR) signaling in cell and animal models
(2) Define TOR pathways and establish the global TOR signaling network in budding yeast using genetic. cell biological. chemical genomic and bioinformatic tools
(3) Study the control of chromatin structures as a novel form of regulation of gene expression in response to extracellular growth signals
(4) Developing small molecule modulators of mTOR pathways and growth-related diseases using chemical genetic. genomic and bioinformatic tools.

Selected Publications

Zhang YJ, Duan Y, Zheng XF. (2011) Targeting the mTOR kinase domain: the second generation of mTOR inhibitors. Drug Discov Today. Apr;16(7-8):325-31.

Wei Y, Zheng XS. (2010) Maf1 regulation: A model of signal transduction inside the nucleus. Nucleus. Mar;1(2):162-165.

Don AS, Zheng XF. (2011) Recent clinical trials of mTOR-targeted cancer therapies. Rev Recent Clin Trials. Jan;6(1):24-35.

Tsang CK, Liu H, Zheng XF. (2010) mTOR binds to the promoters of RNA polymerase I- and III-transcribed genes. Cell Cycle. Mar 1;9(5):953-7.

Wei Y, Zheng XF. (2009) TORC1 association with rDNA chromatin as a mechanism to co-regulate Pol I and Pol III. Cell Cycle. 8(23):3802-3.

Wei Y, Zheng XF. (2009) Sch9 partially mediates TORC1 signaling to control ribosomal RNA synthesis. Cell Cycle. 8(24).

Wei, Y.H., Tsang, C.K., and Zheng, X.F. (2009) Regulatory mechanisms of Pol III-dependent transcription by TORC. The EMBO Journal 28: 2220-2230.

Wei, Y.H. and Zheng, X.F. (2009) Nutrient Control of Cell Growth via TOR Signaling in Yeast, Yeast Systems Biology: Methods and Protocols, Humana Press.

Tsang, C.K., and Zheng, X.F. Opposing role of condensin and radiation sensitive gene RAD52 in ribosomal DNA (rDNA) stability regulation, J Biol Chem 2009; 284:21908-19

Tsang, C.K. and Zheng, X.F. (2009) Less TORC is more: therapeutic extension of mammalian lifespan. Cell Science Vol 6, No 2.

Qi H, Chen Y, Fu X, Lin CP, Zheng XF, Liu LF. (2008) TOR regulates cell death induced by telomere dysfunction in budding yeast. PLoS ONE. 3(10):e3520.

Tsang CK, Wei Y, Zheng XF. (2007) Compacting DNA during the interphase: condensin maintains rDNA integrity. Cell Cycle. 6(18):2213-8.

Tsang CK, Qi H, Liu LF, Zheng XF. (2007) Targeting mammalian target of rapamycin (mTOR) for health and diseases. Drug Discov Today. 12(3-4):112-24.

Tsang CK, Zheng XF. (2007) TOR-in(g) the nucleus. Cell Cycle. 6(1):25-9.

Liu X, Zheng XF. (2007) Endoplasmic reticulum and Golgi localization sequences for mammalian target of rapamycin. Mol Biol Cell. 18(3):1073-82.

Tsang, C.K., Li, H. and Zheng, X.F. (2007) Nutrient starvation promotes condensin loading to maintain rDNA stability. The EMBO J 26:448-458.

Liu, X.Y. and Zheng, X.F. (2007) ER and Golgi localization sequences for mammalian target of Rapamycin (mTOR). Mol Biol Cell 18:1073-1082.

Tsang, C.K. and Zheng, X.F. (2007) TOR-in(g) the Nucleus. Cell Cycle 6:25 -29.

Tsang, C.K., Qi, H.Y., Liu, L.F. and Zheng, X.F. (2007) Target Rapamycin target: Broad roles of mTOR in human health and diseases. Drug Discovery Today (Keynote Review) 12:112-124.

Li, H., Watkins, M., Tsang, C.K., Bertram, P.G. and Zheng, X.F. (2006) Nutrient regulates Tor1 nuclear localization and association with rDNA promoter. Nature 442:1058-1061 (Featured in Science’s STKE Vol. 2006, Issue 351, pp. tw302, 5 September 2006, and Cell Metabolism 2006, 4:259-260).

Tsang. C.K. and Zheng. X.F. (2004) Control of ribosome biogenesis by target of Rapamycin (TOR). Recent Res. Dev. Mol Cell Biol 5:135.

Drenan. R.. Liu. X.Y.. Bertram. P.G. and Zheng. X.F. (2004). FKBP12-Rapamycin-associated protein or mammalian target of Rapamycin (FRAP/mTOR) localization in the endoplasmic reticulum and the Golgi apparatus. Journal of Biological Chemistry 279:772-228.

Zheng. X.F.. Chan. T.F. and Zhou. H. (2004). Genomic and genetic approaches toward identification and study of the targets of small bioactive molecules. Chemistry and Biology (Review) 11:609-18.

Xu. G.. Zhang. L.H.. Zhao. T.. Bertram. P.B.. Zheng. X.F. and McLeod. H. (2004). Pharmacogenomic profiling of the PI3K/PTEN-AKT-mTOR pathway in common human tumors. International Journal of Oncology 24:893.

Carvalho. J. and Zheng. X.F. (2003). Domains of Gln3p interacting with Karyopherins. Ure2p and target of Rapamycin (TOR). Journal of Biological Chemistry 278:16878-16886.

Tsang. C.K.. Bertram. P.G.. Ai. W.D.. Drenan. R. and Zheng. X.F. (2003). Chromatin-mediated regulation of nucleolar structure and RNA polymerase I localization by TOR. EMBO Journal 22: 6045-6056.