Current Position

Assistant Professor of Microbiology and Immunology, Program in Oncology, Greenebaum Cancer Center and Center for Vascular and Inflammatory Diseases (CVID)

Previous Positions

* Research Scientist, July 2001-July 2004, David W. Scott Group, American Red Cross, Rockville MD

* Research Fellow II, Sept. 1998-July 2001, David W. Scott Group, American Red Cross, Rockville MD

* Research Fellow I, July 1998-Sept. 1998, David W. Scott Group, American Red Cross, Rockville, MD

* Postdoctoral Fellow, Nov 1995-June 1998, Donald Guthrie Research Foundation, Sayre, PA

Education

PhD Biochemistry, 1995, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA

BSc Biology/Chemistry, 1989, Virginia Commonwealth University, Richmond, VA

AA Biology/Chemistry, 1986, College of the Bahamas, Nassau, Bahamas

Our long-range research interests are to explore the mechanism of programmed cell death in tumor cells and especially B-cell lymphomas, via death receptors and by chemotherapeutic agents. We are exploring the notion that controlled oxidation can promote the selective targeting and destruction of critical growth and survival proteins. Our research combines several approaches to potentially target protein kinases in the PI3K/Akt and Ras signaling pathways and to invoke protein phosphatases for the selective killing of lymphomas, prostate and breast cancer cells.

The major ongoing project in the lab is to continue to explore the mechanism of action of Manumycin-A (Man-A), a natural chemotherapeutic, in tumor death. Man-A is a farnesyltransferase inhibitor (FTI) that was originally prospected for its potential in treating Ras-transformed cancers. However, recent mounting evidence, including ours, shows that Man-A can kill tumors independently of Ras and even FTases. Furthermore, synthetic FTIs have been disappointingly ineffective in treating tumors in clinical trials. Our data show that the superiority of Man-A to invoke death may lie in its ability to specifically invoke a cascade of events that lead to apoptotic cell death. These include induction of reactive oxygen species (ROS), increased protein phosphatase activity then the selective, ROS- and caspase-dependent dephosphorylation and cleavage of MEK and Akt. Importantly, ERK2, heat shock and other proteins are not targeted similarly, demonstrating that the process is differentially regulated. We are exploring the notion that ROS can rapidly and specifically target MEK and Akt for dephosphorylation and cleavage under conditions of terminal cellular stress. Since MEK contributes to tumor growth and Akt contributes to tumor survival, growth and proliferation, understanding the molecular basis for the selective targeting of these proteins will lead to the design of therapies that directly target this system in tumors, especially resistant ones. Ultimately, this better understanding will aid the design or screening of better targeted, more potent and less toxic therapies for the treatment of cancer. Funded by NCI CA128882 to GB Carey 9/2007-8/2010.