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

Zhang, Liguo, Nai-Jia Huang, Chen Chen, Wanli Tang, and Sally Kornbluth. “Ubiquitylation of p53 by the APC/C inhibitor Trim39.Proceedings of the National Academy of Sciences of the United States of America 109, no. 51 (December 4, 2012): 20931–36. https://doi.org/10.1073/pnas.1212047110. Full Text Open Access Copy

Johnson, Erika Segear, and Sally Kornbluth. “Life, death, and the metabolically controlled protein acetylome.Current Opinion in Cell Biology 24, no. 6 (December 2012): 876–80. https://doi.org/10.1016/j.ceb.2012.10.002. Full Text

Andersen, Joshua L., and Sally Kornbluth. “Mcl-1 rescues a glitch in the matrix.Nature Cell Biology 14, no. 6 (June 2012): 563–65. https://doi.org/10.1038/ncb2511. Full Text

Califf, Robert M., and Sally Kornbluth. “Establishing a framework for improving the quality of clinical and translational research.J Clin Oncol 30, no. 14 (May 10, 2012): 1725–26. https://doi.org/10.1200/JCO.2011.41.4458. Full Text

Huang, Nai-Jia, Liguo Zhang, Wanli Tang, Chen Chen, Chih-Sheng Yang, and Sally Kornbluth. “The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1.The Journal of Cell Biology 197, no. 3 (April 23, 2012): 361–67. https://doi.org/10.1083/jcb.201111141. Full Text Open Access Copy

Kim, Jiyeon, Amanda B. Parrish, Manabu Kurokawa, Kenkyo Matsuura, Christopher D. Freel, Joshua L. Andersen, Carrie E. Johnson, and Sally Kornbluth. “Rsk-mediated phosphorylation and 14-3-3ɛ binding of Apaf-1 suppresses cytochrome c-induced apoptosis.The Embo Journal 31, no. 5 (March 2012): 1279–92. https://doi.org/10.1038/emboj.2011.491. Full Text

Johnson, Erika Segear, and Sally Kornbluth. “Phosphatases driving mitosis: pushing the gas and lifting the brakes.Progress in Molecular Biology and Translational Science 106 (January 2012): 327–41. https://doi.org/10.1016/b978-0-12-396456-4.00008-0. Full Text

Thomenius, M., C. D. Freel, S. Horn, R. Krieser, E. Abdelwahid, R. Cannon, S. Balasundaram, K. White, and S. Kornbluth. “Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death.Cell Death Differ 18, no. 10 (October 2011): 1640–50. https://doi.org/10.1038/cdd.2011.26. Full Text Open Access Copy

Andersen, Joshua L., J Will Thompson, Kelly R. Lindblom, Erika S. Johnson, Chih-Sheng Yang, Lauren R. Lilley, Christopher D. Freel, M Arthur Moseley, and Sally Kornbluth. “A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2.Mol Cell 43, no. 5 (September 2, 2011): 834–42. https://doi.org/10.1016/j.molcel.2011.07.028. Full Text

Andersen, Joshua L., and Sally Kornbluth. “Meeting the (N-terminal) end with acetylation.Cell 146, no. 4 (August 2011): 503–5. https://doi.org/10.1016/j.cell.2011.07.024. Full Text

Pages

Selected Grants

Regulation of M phase exit awarded by National Institutes of Health (Principal Investigator). 2009 to 2011

Control of Mitotic Entry by Regulators of Cdc2 awarded by National Institutes of Health (Principal Investigator). 2003 to 2011

Research Training In Neuro-Oncology awarded by National Institutes of Health (Mentor). 2005 to 2010

High-performance Computing System for Bioinformatics awarded by National Institutes of Health (Advisor). 2009 to 2010

Apoptotic Signaling Pathways awarded by National Institutes of Health (Principal Investigator). 2000 to 2009

Regulation of Apoptosis awarded by National Institutes of Health (Principal Investigator). 1997 to 2007

Control of The Mitotic Exit by the Xnf7 Ubiquitin Ligase awarded by National Institutes of Health (Principal Investigator). 2004 to 2007

Reaper Mediated Apoptosis awarded by National Institutes of Health (Principal Investigator). 2004 to 2007

Reaper-Scythe Regulated Apoptosis awarded by National Institutes of Health (Principal Investigator). 2004 to 2006

BCR-Abl-mediated inhibition of apoptosis awarded by National Institutes of Health (Principal Investigator). 2003 to 2006

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