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

Horn, Sarah R., Michael J. Thomenius, Erika Segear Johnson, Christopher D. Freel, Judy Q. Wu, Jonathan L. Coloff, Chih-Sheng Yang, et al. “Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability.Mol Biol Cell 22, no. 8 (April 15, 2011): 1207–16. https://doi.org/10.1091/mbc.E10-07-0567. Full Text

Esmaili, Armond M., Erika L. Johnson, Silpa S. Thaivalappil, Helena M. Kuhn, Sally Kornbluth, and Pablo M. Irusta. “Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export.Cell Cycle (Georgetown, Tex.) 9, no. 19 (October 25, 2010): 3913–20. https://doi.org/10.4161/cc.9.19.13138. Full Text

Buchakjian, Marisa R., and Sally Kornbluth. “The engine driving the ship: metabolic steering of cell proliferation and death.Nature Reviews. Molecular Cell Biology 11, no. 10 (October 2010): 715–27. https://doi.org/10.1038/nrm2972. Full Text

Yang, Chih-Sheng, Michael J. Thomenius, Eugene C. Gan, Wanli Tang, Christopher D. Freel, Thomas J. S. Merritt, Leta K. Nutt, and Sally Kornbluth. “Metabolic regulation of Drosophila apoptosis through inhibitory phosphorylation of Dronc.The Embo Journal 29, no. 18 (September 2010): 3196–3207. https://doi.org/10.1038/emboj.2010.191. Full Text

Tang, Wanli, Judy Qiju Wu, Chen Chen, Chih-Sheng Yang, Jessie Yanxiang Guo, Christopher D. Freel, and Sally Kornbluth. “Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism.Molecular Biology of the Cell 21, no. 15 (August 2010): 2589–97. https://doi.org/10.1091/mbc.e09-08-0708. Full Text Open Access Copy

Kurokawa, Manabu, and Sally Kornbluth. “Stalling in mitosis and releasing the apoptotic brake.The Embo Journal 29, no. 14 (July 2010): 2255–57. https://doi.org/10.1038/emboj.2010.150. Full Text

Andrews, Nancy C., Sally Kornbluth, and Doug Stokke. “Women: diversity among leaders is there if you look.Nature 463, no. 7281 (February 4, 2010): 608. https://doi.org/10.1038/463608d. Full Text

Nutt, L. K., M. R. Buchakjian, E. Gan, R. Darbandi, S. Y. Yoon, J. Q. Wu, Y. J. Miyamoto, et al. “Metabolic Control of Oocyte Apoptosis Mediated by 14-3-3ζ-Regulated Dephosphorylation of Caspase-2 (DOI:10.1016/j.devcel.2009.04.005).” Developmental Cell 18, no. 1 (January 19, 2010): 165. https://doi.org/10.1016/j.devcel.2010.01.005. Full Text

Feng, Junjie, Timothy Wakeman, Sheila Yong, Xiaohua Wu, Sally Kornbluth, and Xiao-Fan Wang. “Protein phosphatase 2A-dependent dephosphorylation of replication protein A is required for the repair of DNA breaks induced by replication stress.Mol Cell Biol 29, no. 21 (November 2009): 5696–5709. https://doi.org/10.1128/MCB.00191-09. Full Text

Pages