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

Kurokawa, Manabu, Chen Zhao, Tannishtha Reya, and Sally Kornbluth. “Inhibition of apoptosome formation by suppression of Hsp90beta phosphorylation in tyrosine kinase-induced leukemias.Molecular and Cellular Biology 28, no. 17 (September 2008): 5494–5506. https://doi.org/10.1128/mcb.00265-08. Full Text

Tang, Wanli, Judy Qiju Wu, Yanxiang Guo, David V. Hansen, Jennifer A. Perry, Christopher D. Freel, Leta Nutt, Peter K. Jackson, and Sally Kornbluth. “Cdc2 and Mos regulate Emi2 stability to promote the meiosis I-meiosis II transition.Molecular Biology of the Cell 19, no. 8 (August 2008): 3536–43. https://doi.org/10.1091/mbc.e08-04-0417. Full Text

Guo, Jessie Yanxiang, Ayumi Yamada, Taisuke Kajino, Judy Qiju Wu, Wanli Tang, Christopher D. Freel, Junjie Feng, et al. “Aven-dependent activation of ATM following DNA damage.Curr Biol 18, no. 13 (July 8, 2008): 933–42. https://doi.org/10.1016/j.cub.2008.05.045. Full Text

Wu, Judy Qiju, and Sally Kornbluth. “Not-so-pseudo a substrate: Acm1-mediated inhibition of the APC.Molecular Cell 30, no. 5 (June 2008): 543–44. https://doi.org/10.1016/j.molcel.2008.05.011. Full Text

Freel, Christopher D., D Ashley Richardson, Michael J. Thomenius, Eugene C. Gan, Sarah R. Horn, Michael R. Olson, and Sally Kornbluth. “Mitochondrial localization of Reaper to promote inhibitors of apoptosis protein degradation conferred by GH3 domain-lipid interactions.J Biol Chem 283, no. 1 (January 4, 2008): 367–79. https://doi.org/10.1074/jbc.M708931200. Full Text

Johnson, Carrie E., Yolanda Y. Huang, Amanda B. Parrish, Michelle I. Smith, Allyson E. Vaughn, Qian Zhang, Kevin M. Wright, et al. “Differential Apaf-1 levels allow cytochrome c to induce apoptosis in brain tumors but not in normal neural tissues.Proceedings of the National Academy of Sciences of the United States of America 104, no. 52 (December 18, 2007): 20820–25. https://doi.org/10.1073/pnas.0709101105. Full Text Open Access Copy

Wang, Michael Zhuo, Judy Qiju Wu, Arlene S. Bridges, Darryl C. Zeldin, Sally Kornbluth, Richard R. Tidwell, James Edwin Hall, and Mary F. Paine. “Human enteric microsomal CYP4F enzymes O-demethylate the antiparasitic prodrug pafuramidine.Drug Metabolism and Disposition: The Biological Fate of Chemicals 35, no. 11 (November 2007): 2067–75. https://doi.org/10.1124/dmd.107.016428. Full Text

Wu, Judy Qiju, David V. Hansen, Yanxiang Guo, Michael Zhuo Wang, Wanli Tang, Christopher D. Freel, Jeffrey J. Tung, Peter K. Jackson, and Sally Kornbluth. “Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A.Proceedings of the National Academy of Sciences of the United States of America 104, no. 42 (October 2007): 16564–69. https://doi.org/10.1073/pnas.0707537104. Full Text Open Access Copy

Zhu, Wenge, Chinweike Ukomadu, Sudhakar Jha, Takeshi Senga, Suman K. Dhar, James A. Wohlschlegel, Leta K. Nutt, Sally Kornbluth, and Anindya Dutta. “Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.Genes & Development 21, no. 18 (September 2007): 2288–99. https://doi.org/10.1101/gad.1585607. Full Text Open Access Copy

Rathmell, Jeffrey C., and Sally Kornbluth. “Filling a GAP(DH) in caspase-independent cell death.Cell 129, no. 5 (June 1, 2007): 861–63. https://doi.org/10.1016/j.cell.2007.05.030. Full Text

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