Sally A. Kornbluth

Jo Rae Wright University 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

Matsuura, K, Huang, N-J, Cocce, K, Zhang, L, and Kornbluth, S. "Downregulation of the proapoptotic protein MOAP-1 by the UBR5 ubiquitin ligase and its role in ovarian cancer resistance to cisplatin." Oncogene 36, no. 12 (March 2017): 1698-1706. Full Text

Foss, KM, Robeson, AC, Kornbluth, S, and Zhang, L. "Mitotic phosphatase activity is required for MCC maintenance during the spindle checkpoint." Cell cycle (Georgetown, Tex.) 15, no. 2 (January 2016): 225-233. Full Text

Kornbluth, S, and Fissore, R. "Vertebrate Reproduction." Cold Spring Harbor perspectives in biology 7, no. 10 (October 2015): a006064-. (Review) Full Text

Machado, MV, Michelotti, GA, Pereira, TDA, Boursier, J, Kruger, L, Swiderska-Syn, M, Karaca, G, Xie, G, Guy, CD, Bohinc, B, Lindblom, KR, Johnson, E, Kornbluth, S, and Diehl, AM. "Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2 deficient mice with non-alcoholic steatohepatitis." Gut 64, no. 7 (July 2015): 1148-1157. Full Text

Yang, C-S, Matsuura, K, Huang, N-J, Robeson, AC, Huang, B, Zhang, L, and Kornbluth, S. "Fatty acid synthase inhibition engages a novel caspase-2 regulatory mechanism to induce ovarian cancer cell death." Oncogene 34, no. 25 (June 2015): 3264-3272. Full Text

Machado, MV, Michelotti, GA, Pereira, TDA, Boursier, J, Kruger, L, Swiderska-Syn, M, Karaca, G, Xie, G, Guy, CD, Bohinc, B, Lindblom, KR, Johnson, E, Kornbluth, S, and Diehl, AM. "Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2 deficient mice with non-alcoholic steatohepatitis." Gut 64, no. 7 (2015): 1148-1157. Full Text

Huang, B, Yang, C-S, Wojton, J, Huang, N-J, Chen, C, Soderblom, EJ, Zhang, L, and Kornbluth, S. "Metabolic control of Ca2+/calmodulin-dependent protein kinase II (CaMKII)-mediated caspase-2 suppression by the B55β/protein phosphatase 2A (PP2A)." The Journal of biological chemistry 289, no. 52 (December 2014): 35882-35890. Full Text

Lindblom, K, and Kornbluth, S. "The complex interplay between metabolism and apoptosis." 9781461493020 (November 1, 2014): 189-209. (Chapter) Full Text

Kornbluth, S, and Sedwick, C. "Sally Kornbluth: Nature's incredible contraptions." The Journal of Cell Biology 206, no. 1 (July 2014): 4-5. (Interview) Full Text

Yang, CS, Sinenko, SA, Thomenius, MJ, Robeson, AC, Freel, CD, Horn, SR, and Kornbluth, S. "The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis." Cell Death and Differentiation 21, no. 4 (April 1, 2014): 604-611. Full Text

Pages

Casaletto, JB, Moore, JD, Etkin, LD, and Kornbluth, SA. "Xnf7 and the regulation of Xenopus cyclin B2." November 2002.

Medical Scientist Training Program awarded by National Institutes of Health (Mentor). 1997 to 2022

The AMPK/ULK1/p27Kip1 axis regulates autophagy and cell survival in aged satellite cells awarded by National Institutes of Health (Collaborator). 2017 to 2022

Center for Molecular & Cellular Studies of Ped Disease awarded by National Institutes of Health (Mentor). 2003 to 2018

Control of the apoptosome in epithelial ovarian cancer to enhance chemotherapy awarded by National Institutes of Health (Principal Investigator). 2014 to 2017

Provost's Discretionary Fund awarded by Duke Endowment (Principal Investigator). 2014 to 2017

Control of caspase activation in apoptosis awarded by National Institutes of Health (Principal Investigator). 2007 to 2017

Research Training In Neuro-Oncology awarded by National Institutes of Health (Mentor). 1998 to 2016

Cancer Biology Training Grant awarded by National Cancer Institute (Mentor). 1993 to 2016

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

Pages