Assistant Professor of Molecular Biology & Genetics
Publications | Research | Faculty
Background:
Siu Sylvia Lee is an assistant professor in the Department of Molecular Biology and Genetics. She received a B.A. in Biochemistry from Rice University in 1995 and a Ph.D. from Baylor College of Medicine in 1999. She received her postdoctoral training at the Department of Molecular Biology of Massachusetts General Hospital & the Department of Genetics of Harvard Medical School, where she was awarded a Damon Runyon Cancer Foundation Postdoctoral Fellowship.
She joined the faculty at Cornell in 2003. She is in the graduate fields of Genetics & Development, Biochemistry, Molecular, & Cell Biology, and Nutrition. Her research is supported by the National Institute of Aging and the Ellison Medical Foundation. She teaches BioBM/BioGD/Tox437: Regulation of Cell Proliferation, Senescence, and Death.
Although aging is a universal process, little is known about its molecular underpinnings. Our laboratory is interested in elucidating the conserved molecular pathways that modulate longevity. Emerging research has revealed longevity determinants capable of regulating aging in diverse organisms, from yeast, to invertebrates, to mammals, highlighting the high degree of conservation in the molecular mechanisms that govern longevity. Our research focuses on using the powerful genetic model round worm Caenorhabditis elegans to identify and functionally characterized the evolutionarily conserved genetic determinants important for longevity. As a long term goal, we hope to test whether our findings in C. elegans also hold true in other diverse organisms, including fruit flies and mice. A better understanding of the mechanistic basis of aging will have important implications for the prevention and treatment of many crippling age-dependent diseases, such as cancer, late onset diabetes, and neurodegeneration.
Insulin/insulin growth factor signaling (IIS) is well established to play critical roles in metabolism, development, and longevity in diverse species. The IIS signal transduction cascade in C. elegans is entirely homologous to that in mammals. In C. elegans, signaling from the DAF-2/insulin/IGF receptor antagonizes the activities of the FOXO transcription factor DAF-16 (Fig 1). We have combined comparative genomics with biochemical and functional assays in C. elegans to identify evolutionarily conserved downstream effectors of IIS. We expect that the continued characterization of the DAF-16/FOXO downstream targets will shed light on how IIS mediates its conserved function in development, metabolism, and longevity.
Fig. 1
We also utilized high-throughput RNA-interference (RNAi) screens to systematically identify new longevity genes in C. elegans. We recently completed a genome-wide RNAi screen in which we inactivated each of the ~17,000 predicted ORFs in the C. elegans genome to identify gene knock downs that caused lifespan extension. Our RNAi screen was validated by the identification of known lifespan regulators. Importantly, the RNAi screen yielded a large number of new genes not previously implicated in longevity control, many of which have mammalian homologs (Fig. 2). This type of comprehensive screen provides a global view of the gene classes and cellular processes most relevant to longevity. We have begun detailed characterization of a subset of these new longevity genes using a combination of genetics, molecular and biochemical approaches. The further functional characterization of these candidate longevity genes will provide new insights into the diverse pathways that regulate organismal aging.
Fig. 2
For more information on our research, please visit the Lee lab website.
Click here to view Dr. Lee's PubMed listings.
- J. Li, M. Tewari, M. Vidal, and S. S. Lee. 2007. The 14-3-3 protein FTT-2 regulates DAF-16 in Caenorhabditis elegans. Dev. Biol. 301(1):82-91.
- E.R. Troemel, S.W. Chu, V. Reinke, S. S. Lee, F.M. Ausubel, D.H. Kim. 2006. p38 MAPK Regulates Expression of Immune Response Genes and Contributes to Longevity in C. elegans. Plos Genet. 2(11):e183.
- Lee, S. S. Whole genome RNAi screens for increased longevity: Important new insights but not the whole story. Exp Gerontol. 41(10):968-73.
- Lee SS. Interfering with longevity. Sci Aging Knowledge Environ. 2005 Aug 31;2005(35):pe26.
- Hamilton B, Dong Y, Shindo M, Liu W, Odell I, Ruvkun G, Lee SS. A systematic RNAi screen for longevity genes in C. elegans. 2005. Genes Dev. 19(13): 1544-55.
- Lee, S. S. 2004. Come One, Come All. Sci. Aging Knowl. Environ., Vol. 2004, Issue 18, pp. pe18.
- Lee, S. S., Kennedy, S., Tolonen, A., and Ruvkun, G. 2003. DAF-16 target genes that control C. elegans lifespan and metabolism. Science, 300: 644-647.
- Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., and Ruvkun, G. 2003. A systematic RNAi screen reveals a critical role for mitochondria in C. elegans longevity. Nature Genetics 33: 40-48.
- Frese, K. K., Lee, S. S., Thomas, D. L., Latorre, I. J., Weiss, R. S., Glaunsinger, B. A., and Javier, R. T. 2003. Selective PDZ protein-dependent stimulation of phosphatidylinositol 3-kinase by the adenovirus E4-ORF1 oncoprotein. Oncogene 22: 710-721.
- Lee, S. S. and Ruvkun, G. 2002. Longevity: don't hold your breath. Nature 418: 287-288.
- Glaunsinger, B. A., Weiss, R. S., Lee, S. S., and Javier, R. T. 2001. Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 oncoprotein to a select interaction with the candidate tumor suppressor protein ZO-2. EMBO J. 20: 5578-5586.
- Glaunsinger, B., Lee, S. S., Thomas, M., Banks, L., and Javier, R. 2000. Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and papillomavirus E6 oncoproteins. 2000. Oncogene 19: 5270-5280.
- Lee, S. S., Glaunsinger, B., Mantovani, F., Banks, L., and Javier, R. 2000. The multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins. J. Virol. 74: 9680-9693.
- Barritt, D., Pearn, M., Zisch, A., Lee, S. S., Javier, R., Pasquale, E., and Stallcup, W. 2000. The multi-PDZ domain protein MUPP1 is a cytoplasmic ligand for the membrane-spanning proteoglycan NG2. J. Cellular Biochem. 79: 213-224.
- Gardiol, D., Kuhne, C., Glaunsinger, B., Lee, S. S., Javier R., and Banks, L. 1999. Oncogenic human papillomavirus E6 proteins target the discs large tumor suppressor for proteasome-mediated degradation. Oncogene 18: 5487-5496.
- Lee, S. S., Weiss, R. S., and Javier, R. T. 1997. Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc. Natl. Acad. Sci. USA. 94: 6670-6675.
- Weiss, R. S., Lee, S. S., Prasad, B. V. V., and Javier, R. T. 1997. Human adenovirus early region 4 open reading frame 1 genes encode growth-transforming proteins that may be distantly related to dUTP pyrophosphatase enzymes. J. Virol. 71: 1857-1870.