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

Deming, Paula, and Sally Kornbluth. “Study of apoptosis in vitro using the Xenopus egg extract reconstitution system.Methods in Molecular Biology (Clifton, N.J.) 322 (January 2006): 379–93. https://doi.org/10.1007/978-1-59745-000-3_27. Full Text

Nutt, Leta K., Seth S. Margolis, Mette Jensen, Catherine E. Herman, William G. Dunphy, Jeffrey C. Rathmell, and Sally Kornbluth. “Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2.Cell 123, no. 1 (October 7, 2005): 89–103. https://doi.org/10.1016/j.cell.2005.07.032. Full Text

Kornbluth, Sally, and Kristin White. “Apoptosis in Drosophila: neither fish nor fowl (nor man, nor worm).Journal of Cell Science 118, no. Pt 9 (May 2005): 1779–87. https://doi.org/10.1242/jcs.02377. Full Text Open Access Copy

Casaletto, Jessica B., Leta K. Nutt, Qiju Wu, Jonathan D. Moore, Laurence D. Etkin, Peter K. Jackson, Tim Hunt, and Sally Kornbluth. “Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase.The Journal of Cell Biology 169, no. 1 (April 2005): 61–71. https://doi.org/10.1083/jcb.200411056. Full Text Open Access Copy

Yamada, Ayumi, Brad Duffy, Jennifer A. Perry, and Sally Kornbluth. “DNA replication checkpoint control of Wee1 stability by vertebrate Hsl7.The Journal of Cell Biology 167, no. 5 (December 2004): 841–49. https://doi.org/10.1083/jcb.200406048. Full Text

Deming, Paula B., Zachary T. Schafer, Jessica S. Tashker, Malia B. Potts, Mohanish Deshmukh, and Sally Kornbluth. “Bcr-Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release.Molecular and Cellular Biology 24, no. 23 (December 2004): 10289–99. https://doi.org/10.1128/mcb.24.23.10289-10299.2004. Full Text

Saxena, Sandeep, Ping Yuan, Suman Kumar Dhar, Takeshi Senga, David Takeda, Howard Robinson, Sally Kornbluth, Kunchithapadam Swaminathan, and Anindya Dutta. “A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition.Molecular Cell 15, no. 2 (July 2004): 245–58. https://doi.org/10.1016/j.molcel.2004.06.045. Full Text

Margolis, Seth S., and Sally Kornbluth. “When the checkpoints have gone: insights into Cdc25 functional activation.Cell Cycle (Georgetown, Tex.) 3, no. 4 (April 2004): 425–28.

Margolis, S. S., and S. Kornbluth. “When the checkpoints have gone: Insights into Cdc25 functional activation.” Cell Cycle 3, no. 4 (January 1, 2004): 423–26. https://doi.org/10.4161/cc.3.4.817. Full Text

Kornbluth, Sally, and Jonathon Pines. “Cell division, growth and death. Cell growth: live and let die.Current Opinion in Cell Biology 15, no. 6 (December 2003): 645–47. https://doi.org/10.1016/j.ceb.2003.10.017. Full Text

Pages