Sally A. Kornbluth

Jo Rae Wright University Distinguished Professor

Office: 
421 Chapel Drive, 220 Allen Building, Durham, NC 27708
Campus Box: 
90005, Durham, NC 27708
Phone: 
(919) 684-2631
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

Powers, M., E. K. Evans, J. Yang, and S. Kornbluth. “Preparation and use of interphase Xenopus egg extracts.Current Protocols in Cell Biology Chapter 11 (May 2001): Unit-11.10. https://doi.org/10.1002/0471143030.cb1110s09. Full Text

Thress, K., J. Song, R. I. Morimoto, and S. Kornbluth. “Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper.The Embo Journal 20, no. 5 (March 2001): 1033–41. https://doi.org/10.1093/emboj/20.5.1033. Full Text

Olson, M., and S. Kornbluth. “Mitochondria in apoptosis and human disease.Current Molecular Medicine 1, no. 1 (March 2001): 91–122. https://doi.org/10.2174/1566524013364239. Full Text

Yang, J., H. Song, S. Walsh, E. S. Bardes, and S. Kornbluth. “Combinatorial control of cyclin B1 nuclear trafficking through phosphorylation at multiple sites.The Journal of Biological Chemistry 276, no. 5 (February 2001): 3604–9. https://doi.org/10.1074/jbc.m008151200. Full Text

Smith, J. J., E. K. Evans, M. Murakami, M. B. Moyer, M. A. Moseley, G. Vande Woude, and S. Kornbluth. “Wee1-regulated apoptosis mediated by the crk adaptor protein in Xenopus egg extracts.J Cell Biol 151, no. 7 (December 25, 2000): 1391–1400. https://doi.org/10.1083/jcb.151.7.1391. Full Text Open Access Copy

Winkler, K. E., K. I. Swenson, S. Kornbluth, and A. R. Means. “Requirement of the prolyl isomerase Pin1 for the replication checkpoint.Science 287, no. 5458 (March 3, 2000): 1644–47. https://doi.org/10.1126/science.287.5458.1644. Full Text

Kaye, F. J., S. Modi, I. Ivanovska, E. V. Koonin, K. Thress, A. Kubo, S. Kornbluth, and M. D. Rose. “A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like Stch.Febs Letters 467, no. 2–3 (February 2000): 348–55. https://doi.org/10.1016/s0014-5793(00)01135-2. Full Text

Thress, K., E. K. Evans, and S. Kornbluth. “Reaper-induced dissociation of a Scythe-sequestered cytochrome c-releasing activity.The Embo Journal 18, no. 20 (October 1999): 5486–93. https://doi.org/10.1093/emboj/18.20.5486. Full Text

Thress, K., S. Kornbluth, and J. J. Smith. “Mitochondria at the crossroad of apoptotic cell death.Journal of Bioenergetics and Biomembranes 31, no. 4 (August 1999): 321–26. https://doi.org/10.1023/a:1005471701441. Full Text

Yang, J., and S. Kornbluth. “All aboard the cyclin train: subcellular trafficking of cyclins and their CDK partners.Trends in Cell Biology 9, no. 6 (June 1999): 207–10. https://doi.org/10.1016/s0962-8924(99)01577-9. Full Text

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