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Sally Kornbluth

Provost of Duke University and James B Duke Professor
Pharmacology and Cancer Biology
919 668 4729
Research Interest: 
Cell cycle
Signal transduction
Research Summary: 
The basic biology of programmed cell death (apoptosis) and cell cycle progression as well as the potential for modulating these signaling pathways to enhance cancer therapy.
Research Description: 

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 the regulation of apoptosis by metabolism, control of exit from mitosis, and the mechanisms underlying inhibition of apoptosis in cancer cells. We are also exploring avenues for manipulating these signaling pathways to enhance cancer therapy.
To address these problems, we use mammalian systems (tissue culture and mouse models) and 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.
For the study of apoptosis, modifications in extract preparation have allowed us to produce extracts which can accurately reproduce the biochemical events of apoptosis, including mitochondrial cytochrome c release and activation of apoptotic proteases, the caspases. These powerful in vitro approaches allow us to isolate novel cell death/cell cycle regulators which we can then assay functionally both in vitro and in intact mammalian cell systems. Using these molecular and biochemical approaches, we are working towards the elucidation of signaling pathways required for cell proliferation and cell death.

A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2.
Andersen JL, Thompson JW, Lindblom KR, Johnson ES, Yang CS, Lilley LR, Freel CD, Moseley MA, Kornbluth S.
Mol Cell. 2011. 43:834-42.

Inhibition of apoptosome formation by suppression of Hsp90beta phosphorylation in tyrosine kinase-induced leukemias.
Kurokawa M, Zhao C, Reya T, Kornbluth S.
Mol Cell Biol. 2008. 28:5494-506.

Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2.
Nutt LK, Buchakjian MR, Gan E, Darbandi R, Yoon SY, Wu JQ, Miyamoto YJ, Gibbons JA, Gibbon JA, Andersen JL, Freel CD, Tang W, He C, Kurokawa M, Wang Y, Margolis SS, Fissore RA, Kornbluth S.
Dev Cell. 2009. 16:856-66.

Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.
Margolis SS, Perry JA, Forester CM, Nutt LK, Guo Y, Jardim MJ, Thomenius MJ, Freel CD, Darbandi R, Ahn JH, Arroyo JD, Wang XF, Shenolikar S, Nairn AC, Dunphy WG, Hahn WC, Virshup DM, Kornbluth S.
Cell. 2006. 127:759-73.

PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation.
Wu JQ, Guo JY, Tang W, Yang CS, Freel CD, Chen C, Nairn AC, Kornbluth S.
Nat Cell Biol. 2009. 11:644-51.