John Sedivy, Brown University, USA
John Sedivy

I have had a long-standing interest in molecular genetics, signaling and cell cycle control. As a postdoc I developed one of the first methods for targeted homologous recombination, which I subsequently used to construct gene knockouts in somatic cells. In 1995 my lab isolated a knockout of c-Myc in a rat fibroblast cell line, which led to my career-long interest in this proto-oncogene. In 1997 my lab was the first to achieve a homozygous gene knockout in primary human cells, knocking out the CDKN1A gene (cyclin-dependent kinase inhibitor p21), which initiated my entry into the field of cellular senescence. In 2002 we performed a genetic epistasis analysis to show that cellular senescence was regulated in parallel by the p53-p21 and p16-pRb pathways. In 2004 we developed a reliable single-cell biomarker of telomere-initiated senescence and delineated the signaling pathway between dysfunctional telomeres and the cell cycle. In 2006 we published the first in vivo quantification of cellular senescence in aging primates. My interests subsequently evolved towards the biology of aging, studying whole genome chromatin changes, which recently led to the discovery of the age-associated activation of retrotransposable elements in somatic cells.

1978 B.Sc. Zoology, University of Toronto, Ontario, Canada
1984 Ph.D. Microbiology, Harvard Medical School, Boston, Massachusetts, USA

1984–1988         Postdoctoral Fellow, Massachusetts Institute of Technology
Phillip A. Sharp, supervisor
1988–1993         Assistant Professor, Department of Molecular Biophysics and Biochemistry,       Yale University
1993–1995         Associate Professor, Department of Molecular Biophysics and Biochemistry,      Yale University
1996–1998         Associate Professor, Department of Molecular Biology, Cell Biology and            Biochemistry, Brown University
1998–present      Professor, Department of Molecular Biology, Cell Biology and Biochemistry,     Brown University
2005–2009         Chair, Department of Molecular Biology, Cell Biology and Biochemistry,           Brown University
2006–2009         Director, Center for Genomics and Proteomics, Brown University

(Major Research Interest)
Aging, Cellular senescence, Chromatin, Retrotransposable elements

(Selected recent publications)
1. Criscione, S.W., De Cecco, M., Siranosian, B., Zhang, Y., Kreiling, J.A., Sedivy, J.M. and Neretti, N. (2016). Reorganization of chromosome architecture in replicative cellular senescence. Science Advances 2: e1500882.
2. Hofmann, J.W., Zhao, X., De Cecco, M., Peterson, A.L., Pagliaroli, L., Manivannan, J., Hubbard, G.B., Ikeno, Y., Zhang, Y., Feng, B., Li, X., Serre, T., Qi, W., Van Remmen, H., Miller, R.A., Bath, K.G., de Cabo, R., Xu, H., Neretti, N. and Sedivy, J.M. (2015). Reduced expression of MYC increases longevity and enhances healthspan. Cell 160: 477-488.
3. Gorbunova, V., Boeke, J.D., Helfand, S.L. and Sedivy, J.M. (2014). Sleeping dogs of the genome: Retrotransposable elements may be agents of somatic diversity, disease and aging. Science 346: 1187-1188.
4. De Cecco, M., Criscione, S.W., Peckham, E.J., Hillenmeyer, S., Hamm, E.A., Manivannan, J., Peterson, A.L., Kreiling, J.A., Neretti, N. and Sedivy, J.M. (2013). Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell 12: 247-256.
5. Herbig, U., Ferreira, M., Condel, L., Carey, D. and Sedivy, J.M. (2006). Cellular senescence in aging primates. Science 311: 1257.
6. Guney, I., Wu, S. and Sedivy, J.M. (2006). Reduced c-Myc signaling triggers telomere-independent senescence by regulating the polycomb repressor Bmi-1 and the CDK inhibitor p16INK4a. Proc. Natl. Acad. Sci. USA 103: 3645-3650.
7. Herbig, U., Jobling, W.A., Chen, B.P.C., Chen, D.J. and Sedivy, J.M. (2004). Telomere shortening triggers replicative senescence of human cells through a signaling pathway involving ATM, p53 and p21CIP1 but not p16INK4a. Mol. Cell 14: 501-513.
8. Yeung, K.C., Seitz, T., Li, S., Janosch, P., McFerran, B., Kaiser, C., Fee, F., Katsanakis, K.D., Rose, D.W., Mischak, H., Sedivy, J.M. and Kolch, W. (1999). Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature 401: 173-177.
9. Brown, J.P., Wei, W. and Sedivy, J.M. (1997). Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 277: 831-834.

Department of Molecular Biology, Cell Biology and Biochemistry
Brown University
70 Ship Street
Providence, RI 20903, USA
Tel: 401 863 7631
E-mail: john_sedivy@brown.edu




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