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

Kornbluth, Sally, and Caitlin Sedwick. “Sally Kornbluth: Nature's incredible contraptions.The Journal of Cell Biology 206, no. 1 (July 2014): 4–5. https://doi.org/10.1083/jcb.2061pi. Full Text

Yang, C. -. S., S. A. Sinenko, M. J. Thomenius, A. C. Robeson, C. D. Freel, S. R. Horn, and S. Kornbluth. “The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis.Cell Death Differ 21, no. 4 (April 2014): 604–11. https://doi.org/10.1038/cdd.2013.184. Full Text

Yang, C. -. S., K. Matsuura, N. -. J. Huang, A. C. Robeson, B. Huang, L. Zhang, and S. Kornbluth. “Fatty acid synthase inhibition engages a novel caspase-2 regulatory mechanism to induce ovarian cancer cell death.” Oncogene, 2014. https://doi.org/10.1038/onc.2014.271. Full Text

Chen, Chen, Liguo Zhang, Nai-Jia Huang, Bofu Huang, and Sally Kornbluth. “Suppression of DNA-damage checkpoint signaling by Rsk-mediated phosphorylation of Mre11.Proceedings of the National Academy of Sciences of the United States of America 110, no. 51 (December 2, 2013): 20605–10. https://doi.org/10.1073/pnas.1306328110. Full Text Open Access Copy

Johnson, Erika Segear, Kelly R. Lindblom, Alexander Robeson, Robert D. Stevens, Olga R. Ilkayeva, Christopher B. Newgard, Sally Kornbluth, and Joshua L. Andersen. “Metabolomic profiling reveals a role for caspase-2 in lipoapoptosis.J Biol Chem 288, no. 20 (May 17, 2013): 14463–75. https://doi.org/10.1074/jbc.M112.437210. Full Text

Kurokawa, Manabu, Jiyeon Kim, Joseph Geradts, Kenkyo Matsuura, Liu Liu, Xu Ran, Wenle Xia, et al. “A network of substrates of the E3 ubiquitin ligases MDM2 and HUWE1 control apoptosis independently of p53.Sci Signal 6, no. 274 (May 7, 2013): ra32. https://doi.org/10.1126/scisignal.2003741. Full Text Open Access Copy

Kurokawa, Manabu, Takahiro Ito, Chih-Sheng Yang, Chen Zhao, Andrew N. Macintyre, David A. Rizzieri, Jeffrey C. Rathmell, Michael W. Deininger, Tannishtha Reya, and Sally Kornbluth. “Engineering a BCR-ABL-activated caspase for the selective elimination of leukemic cells.Proc Natl Acad Sci U S A 110, no. 6 (February 5, 2013): 2300–2305. https://doi.org/10.1073/pnas.1206551110. Full Text Open Access Copy

Andersen, Joshua L., and Sally Kornbluth. “The tangled circuitry of metabolism and apoptosis.Molecular Cell 49, no. 3 (February 2013): 399–410. https://doi.org/10.1016/j.molcel.2012.12.026. Full Text

Parrish, A. B., C. D. Freel, and S. Kornbluth. “Cellular mechanisms controlling caspase activation and function.” Cold Spring Harbor Perspectives in Medicine 3, no. 1 (January 1, 2013).

Parrish, A. B., C. D. Freel, and S. Kornbluth. “Cellular mechanisms controlling caspase activation and function.” Cold Spring Harbor Perspectives in Medicine 3, no. 3 (2013).

Pages

Selected Grants

Inhibition of Cytochrome c-induced Caspase Activation awarded by National Institutes of Health (Principal Investigator). 2003 to 2016

Apoptosome Regulation in Leukemia by Protein Phosphatase 5 Hypoacetylation awarded by National Institutes of Health (Principal Investigator). 2013 to 2015

Regulation of REDD1 and caspase-2 by FASN inhibition in ovarian cancer awarded by National Institutes of Health (Principal Investigator). 2014 to 2015

Integrating Population and Basic Science in Cancer Research awarded by National Institutes of Health (Advisor). 2009 to 2015

Instrumentation for Quantitative Phosphoproteomics and Acetylomics awarded by National Institutes of Health (Major User). 2014 to 2015

Automated detection of protein crystals in high-throughput crystallography experiments awarded by North Carolina Biotechnology Center (Major User). 2014 to 2015

Engineering tyrosine kinase-activated caspases for selective cancer cell killing awarded by National Institutes of Health (Principal Investigator). 2010 to 2014

Metabolic Regulation of 14-3-3zeta Acetylation in Breast Cancer awarded by National Institutes of Health (Principal Investigator). 2012 to 2014

Glucose metabolism and cell death in cancer awarded by National Institutes of Health (Significant Contributor). 2007 to 2014

Molecular mechanisms of chemoresistance in breast cancer awarded by National Institutes of Health (Mentor). 2010 to 2012

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