Protocols assessing mitochondrial changes induced by anti-cancer agents and screening procedures for novel pro-apoptotic agents associated with mitochondria.

The mitochondria are considered the "central executioners" in many apoptotic pathways, especially those invoked by chemotherapeutic agents. Signaling or damage to the mitochondria in the presence of certain chemotherapeutic agents induces the release of cytochrome c and other pro-apoptotic factors such as Smac/DIABLO. Subsequent to the release of cytochrome c into the cytosol is the formation of the "apoptosome", followed by caspase activation and cell death. Agents designed to trigger the release of apoptogenic factors or support the apoptotic process may provide a useful strategy for anti-cancer therapy.

We are engaged in several strategies for discovery of novel anti-cancer drugs within the NCI drug repository (over 200,000 small molecules are unique to this library). For example, we employ high throughput screening (with fluorescence polarization) to search for small molecule mimics of a pro-apoptotic molecule (Smac/DIABLO). Submitochondrial particles are used in the search for inhibitors of electron transport which may promote apoptosis. We implement a variety of assays utilizing isolated rat liver mitochondria, bovine heart submitochondrial particles or permeabilized cells of the 60-cell line screen in order to characterize novel compounds and established anti-cancer agents with respect to their effect on mitochondria and apoptosis.

Credentials

Dr. Glover received her B.S. in Biology from Georgia State University, M.S. in Biology from Towson State University, Ph.D. in Biochemistry from George Washington University (1995). She has participated in cancer research for twenty years.

Recent Publications

NCBI PubMed listing of publications by Constance Glover.