Li, Shang

Research Interests:

The continued proliferation of human cells depends on the proper maintenance of the genomic information encoded in the 46 linear human chromosomes. The stability of these linear chromosomes depends on telomeres, which are maintained by telomerase.

Up-regulation of telomerase is found in more than 85% of human cancers, while telomerase insufficiency can cause early onset of human aging, highlighting the crucial role of telomerase regulation in both cancer therapy and human aging. On the one hand, we would like to inhibit overexpressed telomerase in tumor cells; on the other hand, we need to maintain the telomerase activity of normal stem cells to prevent early onset of aging.

My research goal is to elucidate mechanisms underlying the regulation of telomerase activity in cancer cells and normal stem cells, and to develop novel approaches for therapeutic intervention of human cancer and early onset of aging. Using both yeast and mammalian systems, I will focus on both (1) the regulation of telomerase activity by post-translational modification of telomerase and telomerase-related factors, and (2) the transcriptional regulation of human telomerase reverse transcriptase.

Selected Publications:

Li S., Makovets S., Blethrow J.D., Shokat K.M. and E.H. Blackburn. Cdk1-dependnt phosphorylation of Cdc13 coordinates telomere elongation during cell cycle progression. Cell 136: 50-61 (2009)

Bagheri S., Nosrati M., Li S., Fong S., Torabian S., Rangel J., Moore D.H., Feerman S., Laposa R.R., Baehner F.L., Sagebiel R.W., Cleaver J.E. Haqq C., Debs R.J. Blackburn E.H. and Kashani-Sabet M. Genes and pathways downstream of telomerase in melanoma metastasis. Proc. Natl. Acad. Sci. USA 103: 11306-11311 (2006).

Li S., J. Crothers, C.M. Haqq and E.H. Blackburn. Cellular and gene expression responses involved in the rapid growth inhibition of human cancer cells by RNA interference-mediated depletion of telomerase RNA. J. Biol. Chem. 280:23709-23717 (2005).

Nosrati, M., Li S., S. Bagheri, D. Ginzinger, E.H. Blackburn, R.J. Debs, and M. Kashani-Sabet. Antitumor activity of systemically delivered ribozymes targeting murine telomerase RNA. Clin Cancer Res. 10:4983-4990 (2004).

Li S., J.E. Rosenberg, A.A. Donjacour, I.L. Botchkina, Y.-K. Hom, G.R. Cunha and E.H. Blackburn. Rapid inhibition of cancer cell growth induced by lentiviral expression of mutant-template telomerase RNA constructs and anti-telomerase siRNA. Cancer Res 64: 4833-4840 (2004).

Zheng L., Pan H., Li S., Flesken-Nikitin A., Chen, P.-L., Boyer T.G., and Lee W.-H. Sequence-specific transcriptional co-repressor function for BRCA1 through a novel zinc finger protein, ZBRK1. Mol. Cell. 6: 757-68 (2000).

Li S., Ting N.-S.Y., Zheng L., Ziv Y., Chen P.-L., Shiloh Y., Lee E.-Y. H., and Lee W.-H. Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature 406: 210-215 (2000).

Zhong Q., Chen C.-F., Li S., Chen Y., Wang C.-C., Xiao J., Chen P.-L., Sharp Z. D., and Lee W.-H. Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Science 285: 747-50 (1999).

Li S., Chen P.-L., Subramanian T., Chinnadurai G., Tomlinson G., Kent Osborne C., Sharp Z. D., and Lee W.-H. Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage. J. Biol. Chem. 274: 11334-8 (1999).

Li S., Ku C.-Y., Farmer A., Cong Y.-S., Chen C.-F., and Lee W.-H. Identification of a novel cytoplasmic protein that specifically binds to nuclear localization signal motifs. J. Biol. Chem. 273: 6183-6189 (1998).