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

Evans, E. K., W. Lu, S. L. Strum, B. J. Mayer, and S. Kornbluth. “Crk is required for apoptosis in Xenopus egg extracts.The Embo Journal 16, no. 2 (January 1997): 230–41. https://doi.org/10.1093/emboj/16.2.230. Full Text

Kornbluth, S. “Apoptosis in Xenopus egg extracts.Methods in Enzymology 283 (January 1997): 600–614. https://doi.org/10.1016/s0076-6879(97)83047-9. Full Text

Lew, D. J., and S. Kornbluth. “Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control.Curr Opin Cell Biol 8, no. 6 (December 1996): 795–804. https://doi.org/10.1016/s0955-0674(96)80080-9. Full Text

Chen, J., P. Saha, S. Kornbluth, B. D. Dynlacht, and A. Dutta. “Cyclin-binding motifs are essential for the function of p21CIP1.Molecular and Cellular Biology 16, no. 9 (September 1996): 4673–82. https://doi.org/10.1128/mcb.16.9.4673. Full Text

Kornbluth, S., M. Dasso, and J. Newport. “Evidence for a dual role for TC4 protein in regulating nuclear structure and cell cycle progression.The Journal of Cell Biology 125, no. 4 (May 1994): 705–19. https://doi.org/10.1083/jcb.125.4.705. Full Text

Kornbluth, S., B. Sebastian, T. Hunter, and J. Newport. “Membrane localization of the kinase which phosphorylates p34cdc2 on threonine 14.Molecular Biology of the Cell 5, no. 3 (March 1994): 273–82. https://doi.org/10.1091/mbc.5.3.273. Full Text

Dasso, M., H. Nishitani, S. Kornbluth, T. Nishimoto, and J. W. Newport. “RCC1, a regulator of mitosis, is essential for DNA replication.Molecular and Cellular Biology 12, no. 8 (August 1992): 3337–45. https://doi.org/10.1128/mcb.12.8.3337. Full Text

Kornbluth, S., C. Smythe, and J. W. Newport. “In vitro cell cycle arrest induced by using artificial DNA templates.Molecular and Cellular Biology 12, no. 7 (July 1992): 3216–23. https://doi.org/10.1128/mcb.12.7.3216. Full Text

Mansukhani, A., P. Dell’Era, D. Moscatelli, S. Kornbluth, H. Hanafusa, and C. Basilico. “Characterization of the murine BEK fibroblast growth factor (FGF) receptor: activation by three members of the FGF family and requirement for heparin.Proceedings of the National Academy of Sciences of the United States of America 89, no. 8 (April 1992): 3305–9. https://doi.org/10.1073/pnas.89.8.3305. Full Text Open Access Copy

Dasso, M., C. Smythe, K. Milarski, S. Kornbluth, and J. W. Newport. “DNA replication and progression through the cell cycle.Ciba Foundation Symposium 170 (January 1992): 161–80. https://doi.org/10.1002/9780470514320.ch11. Full Text

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