Pharmacology & Cancer Biology | Duke University Medical Center

Dr. Sally Kornbluth

Sally Kornbluth, Ph.D.
Professor of Pharmacology and Cancer Biology
Vice Dean, Basic Sciences

Duke University Medical Center
C370A LSRC
Box 3813
Durham, NC 27710

Phone: 919-613-8624
E-mail: kornb001@mc.duke.edu

Research Interests

Our lab is interested in the regulation of complex cellular processes, including entry into mitosis and apoptosis (programmed cell death). We are particularly interested in understanding cellular mechanisms which prevent the onset of mitosis prior to the completion of DNA replication and in the tyrosine kinase signaling pathways which impinge upon the decision to apoptose. To address these problems, we use 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 caspases, the apoptotic proteases. These powerful in vitro extracts allow us to examine and dissect critical signaling events by: 1) immunodepletion of cellular components from the extracts 2) addition of exogenously produced recombinant proteins and 3) direct biochemical purification of regulatory proteins. Using these molecular and biochemical approaches, we are working towards the elucidation of signaling pathways required for cell proliferation and cell death.

Publications

Wu, Q, Y. Guo, A.Yamada, J. A. Perry, M.Z. Wang, M. Araki, C. D. Freel, J.J.. Tung, S.S. Margolis, P. K. Jackson, H. Yamano, M. Asano, and S. Kornbluth (2007). A role for Cdc2 and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest. Current Biology, 17: 1-13.

Sasaki, T., E. Gan, A. Wakeham, S. Kornbluth, T.W. Mak, and H. Okada. (2007). HLA-B associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53. Genes
Dev., 21: 848-861.

Zhu, W., C. Ukomadu, T. Senga, S.K. Dhar, J.A. Wohlshlegel, S. Kornbluth, and A. Dutta. (2007). And- 1/CTF4 is a replication factor required for chromatin loading and stability of DNA pol a, Genes Dev, 21: 2288-2299.

Wu, Q, D.V. Hansen, Y. Guo, M.Z. Wang, W. Tang, C.D. Freel, J.J. Tung, P. Jackson and S. Kornbluth. (2007). Control of Emi2 stability and activity through Mos-mediated recruitment of PP2A. Proc. Natl. Acad. Sci USA, 104: 16564-9.

C.E. Johnson, Y, Huang, A.B. Parrish, M.I. Smith, A.E. Vaughn, K.M. Wright, Q. Zhang, T. Van Dyke, R.J. Wechsler-Reya, S. Kornbluth, and M. Deshmukh. (2007). Differential Apaf-1 levels allow Cytochrome c to induce apoptosis in brain tumors but not in normal neural tissues. Proc Natl Acad Sci, USA 104: 20820-5

Schafer, Z.T. and S. Kornbluth (2006). The Apoptosome: Physiological, Developmental, and Pathological Modes of Regulation. Devel. Cell, 10: 549-561.

Margolis, S.S., J.A. Perry, C.M. Forester, L.K. Nutt, Y. Guo, M.J. Jardim, M.J. Thomenius, C.D. Freel, R. Darbandi, J-H Ahn, X-F Wang, S. Shenolikar, A.C. Nairn, W.G. Dunphy, W.C. Hahn, D.M. Virshup, and S. Kornbluth (2006). Role for the PP2A/B56d phosphatase in regulating 14-3-3 release from Cdc25 to control Mitosis. Cell, 127: 759-773.

Colon-Ramos, D.A., C. Shenvy, D.H. Weitzel, E.C.Gan, R. Matts, J. Cate, and S. Kornbluth. (2006). Direct Ribosomal binding by a cellular inhibitor of translation. Nature Structural and Molecular Biol, in press.

Casaletto, J.B., L.K. Nutt, J.D. Moore, Q. Wu, L.D. Etkin, P.K. Jackson, T. Hunt, and S. Kornbluth (2005). Inhibition of the Anaphase-promoting complex by the Xnf7 ubiquitin ligase. J. Cell Biol, 169: 61-71.

Nutt., L.K., S.S. Margolis, M. Jensen, C.E. Herman, W.G. Dunphy, J.C. Rathmell, and S. Kornbluth. (2005). Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase 2. Cell, 123: 89-103.

Saxena, S., P. Yuan, S.K. Dhar, T. Senga, D. Takeda, H. Robinson, S. Kornbluth, K. Swaminathan, and A. Dutta. (2004). A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. Molecular Cell, 15: 245-58.

Deming, P.B., Z.T. Schafer, J.S. Tashker, M. Potts, M.Deshmukh, and S. Kornbluth. (2004). Bcr-Abl-mediated protection from apoptosis downstream of mitochondrial cytochrome c release. Mol. Cell Biol., 24 ; 10289-10299.

Yamada, A., B. Duffy, J.A. Perry, and S. Kornbluth. (2004). DNA replication checkpoint control of Wee1 stability by vertebrate Hsl7, J. Cell Biol., 167: 841-849.

Colon-Ramos, D.A., P.M Irusta, E.C. Gan, M.R. Olson, J. Song, R.I. Morimoto, R.M. Elliott, M. Lombard, R. Hollingsworth, J.M. Hardwick, G.K. Smith, and S. Kornbluth. (2003). Inhibition of translation and induction of apoptosis by Bunyaviral non-structural proteins bearing sequence similarity to Reaper. Mol. Biol. Cell, 14: 4162-4172.

Margolis, S.S., S. Walsh, D.C. Weiser, M. Yoshida, S. Shenolikar, and S. Kornbluth (2003). PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation. EMBOJ, 22: 5734-5745

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