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

Olson, Michael R., Christopher L. Holley, Eugene C. Gan, Daniel A. Colón-Ramos, Bruce Kaplan, and Sally Kornbluth. “A GH3-like domain in reaper is required for mitochondrial localization and induction of IAP degradation.J Biol Chem 278, no. 45 (November 7, 2003): 44758–68. https://doi.org/10.1074/jbc.M308055200. Full Text

Margolis, Seth S., Susan Walsh, Douglas C. Weiser, Minoru Yoshida, Shirish Shenolikar, and Sally Kornbluth. “PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation.Embo J 22, no. 21 (November 3, 2003): 5734–45. https://doi.org/10.1093/emboj/cdg545. Full Text

Colón-Ramos, Daniel A., Pablo M. Irusta, Eugene C. Gan, Michael R. Olson, Jaewhan Song, Richard I. Morimoto, Richard M. Elliott, et al. “Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper.Molecular Biology of the Cell 14, no. 10 (October 2003): 4162–72. https://doi.org/10.1091/mbc.e03-03-0139. Full Text

Olson, Michael R., Christopher L. Holley, Soon Ji Yoo, Jun R. Huh, Bruce A. Hay, and Sally Kornbluth. “Reaper is regulated by IAP-mediated ubiquitination.J Biol Chem 278, no. 6 (February 7, 2003): 4028–34. https://doi.org/10.1074/jbc.M209734200. Full Text

Walsh, Susan, Seth S. Margolis, and Sally Kornbluth. “Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx.Molecular Cancer Research : Mcr 1, no. 4 (February 2003): 280–89.

Moore, Jonathan D., Sally Kornbluth, and Tim Hunt. “Identification of the nuclear localization signal in Xenopus cyclin E and analysis of its role in replication and mitosis.Molecular Biology of the Cell 13, no. 12 (December 2002): 4388–4400. https://doi.org/10.1091/mbc.e02-07-0449. Full Text

Holley, Christopher L., Michael R. Olson, Daniel A. Colón-Ramos, and Sally Kornbluth. “Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition.Nat Cell Biol 4, no. 6 (June 2002): 439–44. https://doi.org/10.1038/ncb798. Full Text

Smith, Jesse J., D Ashley Richardson, Jan Kopf, Minoru Yoshida, Robert E. Hollingsworth, and Sally Kornbluth. “Apoptotic regulation by the Crk adapter protein mediated by interactions with Wee1 and Crm1/exportin.Molecular and Cellular Biology 22, no. 5 (March 2002): 1412–23. https://doi.org/10.1128/mcb.22.5.1412-1423.2002. Full Text

Tashker, Jessica S., Michael Olson, and Sally Kornbluth. “Post-cytochrome C protection from apoptosis conferred by a MAPK pathway in Xenopus egg extracts.Molecular Biology of the Cell 13, no. 2 (February 2002): 393–401. https://doi.org/10.1091/mbc.01-06-0291. Full Text

Kornbluth, S., and E. K. Evans. “Analysis of apoptosis using Xenopus egg extracts.Current Protocols in Cell Biology Chapter 11 (May 2001): Unit-11.12. https://doi.org/10.1002/0471143030.cb1112s09. Full Text

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