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

Perry, J. A., and S. Kornbluth. “Cdc25 and Wee1: Analogous opposites?Cell Division 2 (May 4, 2007). https://doi.org/10.1186/1747-1028-2-12. Full Text Open Access Copy

Sasaki, Toru, Eugene C. Gan, Andrew Wakeham, Sally Kornbluth, Tak W. Mak, and Hitoshi Okada. “HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53.Genes & Development 21, no. 7 (April 2007): 848–61. https://doi.org/10.1101/gad.1534107. Full Text Open Access Copy

Wu, Qiju, Yanxiang Guo, Ayumi Yamada, Jennifer A. Perry, Michael Z. Wang, Marito Araki, Christopher D. Freel, et al. “A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest.Current Biology : Cb 17, no. 3 (February 2007): 213–24. https://doi.org/10.1016/j.cub.2006.12.045. Full Text

Margolis, Seth S., Jennifer A. Perry, Craig M. Forester, Leta K. Nutt, Yanxiang Guo, Melanie J. Jardim, Michael J. Thomenius, et al. “Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.Cell 127, no. 4 (November 17, 2006): 759–73. https://doi.org/10.1016/j.cell.2006.10.035. Full Text

Thomenius, M., and S. Kornbluth. “Multifunctional reaper: sixty-five amino acids of fury.Cell Death and Differentiation 13, no. 8 (August 2006): 1305–9. https://doi.org/10.1038/sj.cdd.4401954. Full Text

Schafer, Zachary T., and Sally Kornbluth. “The apoptosome: physiological, developmental, and pathological modes of regulation.Developmental Cell 10, no. 5 (May 2006): 549–61. https://doi.org/10.1016/j.devcel.2006.04.008. Full Text

Margolis, Seth S., Jennifer A. Perry, Douglas H. Weitzel, Christopher D. Freel, Minoru Yoshida, Timothy A. Haystead, and Sally Kornbluth. “A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25.Mol Biol Cell 17, no. 4 (April 2006): 1779–89. https://doi.org/10.1091/mbc.e05-08-0751. Full Text

Schafer, Zachary T., Amanda B. Parrish, Kevin M. Wright, Seth S. Margolis, Jeffrey R. Marks, Mohanish Deshmukh, and Sally Kornbluth. “Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells.Cancer Res 66, no. 4 (February 15, 2006): 2210–18. https://doi.org/10.1158/0008-5472.CAN-05-3923. Full Text

Colón-Ramos, Daniel A., Christina L. Shenvi, Douglas H. Weitzel, Eugene C. Gan, Robert Matts, Jamie Cate, and Sally Kornbluth. “Direct ribosomal binding by a cellular inhibitor of translation.Nature Structural & Molecular Biology 13, no. 2 (February 2006): 103–11. https://doi.org/10.1038/nsmb1052. Full Text

Kornbluth, Sally, Jing Yang, and Maureen Powers. “Analysis of the cell cycle using Xenopus egg extracts.Current Protocols in Cell Biology Chapter 11 (January 2006): Unit-11.11. https://doi.org/10.1002/0471143030.cb1111s29. Full Text

Pages