Susan L. Smith

Associate Professor, Skirball Institute of Biomolecular Medicine, Molecular Pathogenesis. Department of Pathology. Grad Ad Molecular Onc & Imm Grad Pgm

Ph.D., 1990 SUNY Stony Brook

Lab Website: http://saturn.med.nyu.edu/research/mp/smithlab

Keywords: Telomeres, Sister Chromatid Cohesion, Genome Integrity, Cancer

 

Contact Information: 

Skirball Institute of Biomolecular Medicine
540 First Avenue 2nd floor, Lab 9
New York, N.Y. 10016
Office Tel: (212) 263-2540
Lab Tel: (212) 263-2541
Fax: (212) 263-5711
E-mail: susan.smith@med.nyu.edu

Administrative Contact:

Rachel Frank
Tel: (212)263-6281
Email: rachel.frank@med.nyu.edu


Telomere Function in Aging, Stem Cells, and Cancer

Faithful duplication and segregation of DNA are essential for the continuity of life. Errors in chromosome replication and segregation can lead to aneuploidy, which can have serious consequences for human growth and development, and drive cancer in somatic cells. Telomeres, the ends of eukaryotic chromosomes, require special mechanisms for their protection, replication, and cohesion. We study human telomeres and the mechanisms that control their function in normal cells, stem cells, and in cancer. Human telomere function is regulated by the dedicated six-subunit telomere-binding complex shelterin and by a number of other shelterin-binding factors, such as the poly(ADP-ribose) polymerase tankyrase 1, that associate transiently with telomeres. The goal of our research is to understand how shelterin and its accessory factors regulate telomere structure and function, and control access to telomerase, the reverse transcriptase that adds telomere repeats to chromosome ends.

We have several areas of focus in the lab: 1) the regulation of shelterin stability and function by post-translational modification, including poly(ADP-ribosyl)ation, and ubiquitylation and proteasomal degradation; 2) the mechanisms that control the establishment of sister chromatid cohesion at telomeres during DNA replication and the resolution of sister chromatid cohesion at telomeres in mitosis; 3) the role of defective telomere cohesion in the human stem cell disease dyskeratosis congenita; and 4) the cell cycle regulation and non-telomeric functions of tankyrase 1, including its role at spindle poles and centrosomes. Our long-term goal is to understand the mechanisms that ensure genome integrity and cell survival.

Selected Publications:

Bhanot, M. and Smith S. (2012) TIN2 stability is regulated by the E3 ligase Siah2. Molecular and Cellular Biology 32(2):376-384 PMID: 22064479

Houghtaling, B.R., Canudas, S., and Smith, S. (2012) A Role for sister telomere cohesion in telomere elongation by telomerase. Cell Cycle 11(1):19-25. PMID: 22157096

Bisht, K., Dudognon, C., Chang, W., Sokol, E., Ramirez, A., and Smith, S. (2012) GMD is a cytosolic partner of tankyrase 1 that inhibits its PARP activity. Molecular and Cellular Biology 32(15):3044-3053. PMID: 22645305

Kim, M.K., Dudognon, C., and Smith, S. (2012) Tankyrase 1 regulates centrosome function by controlling CPAP stability. EMBO Reports, 13(8):724-732. PMID: 22699936

Canudas, S., Houghtaling, B.R., Bhanot, M., Sasa, G., Savage, S.A., Bertuch, A.A., and Smith, S. (2011) A role for heterochromatin protein 1γ at human telomeres. Genes & Development 25:1807-1819. PMID: 21865325

Click here to see all publications in PubMed