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

Yang, J., K. Winkler, M. Yoshida, and S. Kornbluth. “Maintenance of G2 arrest in the Xenopus oocyte: a role for 14-3-3-mediated inhibition of Cdc25 nuclear import.The Embo Journal 18, no. 8 (April 1999): 2174–83. https://doi.org/10.1093/emboj/18.8.2174. Full Text

Moore, J. D., J. Yang, R. Truant, and S. Kornbluth. “Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for import of Cdk2/cyclin E and Cdc2/cyclin B1.The Journal of Cell Biology 144, no. 2 (January 1999): 213–24. https://doi.org/10.1083/jcb.144.2.213. Full Text Open Access Copy

Kornbluth, S. “Regulation of apoptotic signaling pathways in cell-free extracts.” Faseb Journal 12, no. 8 (December 1, 1998).

Thress, K., W. Henzel, W. Shillinglaw, and S. Kornbluth. “Scythe: a novel reaper-binding apoptotic regulator.The Embo Journal 17, no. 21 (November 1998): 6135–43. https://doi.org/10.1093/emboj/17.21.6135. Full Text

Crenshaw, D. G., J. Yang, A. R. Means, and S. Kornbluth. “The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1.Embo J 17, no. 5 (August 10, 1998): 1315–27. https://doi.org/10.1093/emboj/17.5.1315. Full Text

Yang, J., E. S. Bardes, J. D. Moore, J. Brennan, M. A. Powers, and S. Kornbluth. “Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1.Genes & Development 12, no. 14 (July 1998): 2131–43. https://doi.org/10.1101/gad.12.14.2131. Full Text Open Access Copy

Kuwana, T., J. J. Smith, M. Muzio, V. Dixit, D. D. Newmeyer, and S. Kornbluth. “Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c.The Journal of Biological Chemistry 273, no. 26 (June 1998): 16589–94. https://doi.org/10.1074/jbc.273.26.16589. Full Text

Sterner, J. M., S. Dew-Knight, C. Musahl, S. Kornbluth, and J. M. Horowitz. “Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7.Molecular and Cellular Biology 18, no. 5 (May 1998): 2748–57. https://doi.org/10.1128/mcb.18.5.2748. Full Text

Evans, E. K., and S. Kornbluth. “Regulation of apoptosis in Xenopus egg extracts.Advances in Enzyme Regulation 38 (January 1998): 265–80. https://doi.org/10.1016/s0065-2571(97)00020-4. Full Text

Evans, E. K., T. Kuwana, S. L. Strum, J. J. Smith, D. D. Newmeyer, and S. Kornbluth. “Reaper-induced apoptosis in a vertebrate system.The Embo Journal 16, no. 24 (December 1997): 7372–81. https://doi.org/10.1093/emboj/16.24.7372. Full Text

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