Sally A. Kornbluth, Jo Rae Wright University Distinguished Professor Emerita
Our lab studies the regulation of complex cellular processes, including cell cycle progression and programmed cell death (apoptosis). These tightly orchestrated processes are critical for appropriate cell proliferation and cell death, and when they go awry can result in cancer and degenerative disorders. Within these larger fields, we have focused on understanding the cellular mechanisms that prevent the onset of mitosis prior to the completion of DNA replication, the processes that prevent cell division when the mitotic spindle is disrupted, the signaling pathways that prevent apoptotic cell death in cancer cells and the mechanisms that link cell metabolism to cell death and survival.
In our quest to answer these important cell biological and biochemical questions, we are varied in our use of experimental systems. Traditionally, we have used cell-free extracts prepared from eggs of the frog Xenopus laevis which can recapitulate cell cycle events and apoptotic processes in vitro. For the study of cell cycle events, extracts are prepared which can undergo multiple rounds of DNA replication and mitosis in vitro. Progression through the cell cycle can be monitored by microscopic observation of nuclear morphology and by biochemically assaying the activity of serine/threonine kinases which control cell cycle transitions.
For the study of apoptosis, modifications in extract preparation have allowed us to produce extracts which can apoptotically fragment nuclei and can accurately reproduce the biochemical events of apoptosis, including internucleosomal DNA cleavage and activation of apoptotic proteases, the caspases.
More recently, we have focused on studying apoptosis and cell cycle progression in mammalian models, both tissue culture cells and mouse models of cancer. In these studies, we are trying to determine the precise signaling mechanisms used by cancer cells to accelerate proliferation and evade apoptotic cell death mechanisms. We also endeavor to subvert these mechanisms to therapeutic advantage. We are particularly interested in links between metabolism and cell death, as high metabolic rates in cancer cells appear to suppress apoptosis to evade chemotherapy-induced cell death.
Finally, we also have several projects using the facile genetics of Drosophila melanogaster to further understand links between metabolism and cell death and also the ways in which mitochondrial dynamics are linked to apoptotic pathways.
Education:
Ph.D., Rockefeller University, 1989
Office Location: 421 Chapel Drive, 220 Allen Building, Durham, NC 27708
Office Phone: +1 919 684 2631
Email Address: kornb001@mc.duke.edu
Additional Web Page: http://sites.duke.edu/kornbluthlab/
Representative Publications (More Publications) (search)
- Deming, P.B., Z.T. Schafer, J.S. Tashker, M. Potts, M.Deshmukh, and S. Kornbluth. (2004). Bcr-
Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release. Mol. Cell Biol., 24: 10289-99.
. - Yamada, A., B. Duffy, J.A. Perry, and S. Kornbluth. (2004). DNA replication checkpoint control
of Wee1 stability by vertebrate Hsl7, J. Cell Biol., 167:841-849. . - Colon-Ramos, D.A., P.M Irusta, E.C. Gan, M.R. Olson, J. Song, R.I. Morimoto, R.M. Elliott, M.
Lombard, R. Hollingsworth, J.M. Hardwick, G.K. Smith, and S. Kornbluth. (2003). Inhibition of
translation and induction of apoptosis by Bunyaviral non-structural proteins bearing sequence
similarity to Reaper. Mol. Biol. Cell, 14: 4162-4172.
. - Margolis, S.S., S. Walsh, D.C. Weiser, M. Yoshida, S. Shenolikar, and S. Kornbluth (2003). PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation. EMBOJ, 22: 5734-5745 .
- Olson, M.R., Holley, C., Gan, E.C., Colon-Ramos, D.A., Kaplan, B., and Kornbluth, S. (2003). A GH3- like domain in Reaper required for mitochondrial localization and induction of IAP degradation. J Biol. Chem, 278: 44758-44768 .
- Holley, C., M. Olson, D. Colon-Ramos, and S. Kornbluth (2002). Reaper eliminates IAP
proteins through stimulated IAP degradation and generalized translational inhibition. Nature Cell Biol, 4: 439-444.
. - Thress, K, Song, J, Morimoto, RI and Kornbluth, S (2001) Reversible inhibition of Hsp 70 chaperone function by Scythe and Reaper. EMBO J 20:1033-1041 .
- Smith, JJ, Evans, EK, Murakami, MB, Moyer, MA, Moseley, G, Vande Woude, G, and Kornbluth S (2000) Wee1-regulated apoptosis mediated by the Crk adaptor protein in Xenopus egg extracts. .