Research Abstract:
The major goals of my research program are to delineate how the cell division cycle is regulated in unperturbed cycling cells (cell cycle control); how cell division is delayed by replicative- and genotoxic-stress (checkpoint control); how cancer cells derail these regulatory pathways and ultimately to use this information to treat human disease. Our current studies focus on (1) cell cycle control, with particular emphasis on the Cdc25 family of protein phosphatases; (2) checkpoint control, with emphasis on the Chk1 and Chk2 protein kinases; (3)establishment and maintenance of cell polarity with emphasis on the Par-1 polarity kinases (4) translational studies in the form of phase I clinical trials and a preclinical model of breast cancer and (5) applying methodologies to noninvasively image endogenous proteins in intact cells and in mice.
Selected Publications:
Kang T, Wei Y, Honaker Y, et al. GSK-3beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3beta inactivation correlates with Cdc25A overproduction in human cancers. Cancer Cell 2008 13: 36-47.
Hurov JB, Huang M, White LS, et al. (2007) Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo. Proc Natl Acad Sci USA 2007 104: 5680-5685.
Leung-Pineda V, Ryan CE, Piwnica-Worms H. Phosphorylation of Chk1 by ATR Is antagonized by a Chk1-regulated protein phosphatase 2A circuit. Mol Cell Biol 2006 26: 7529-7538.
Puc J, Keniry M, Li HS, et al. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell 2005 7:193-204.
Hurov JB, Watkins JL, Piwnica-Worms H. Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity. Curr Biol 2004 14:736-741.
Last Updated: 07/28/2008 |