Dr. Mildred Acevedo-Duncan
Office: VAR 112, CHE 307A
Phone: 813/972-2000 ext 6967,
Lab: VA Hosp 112,116,120
Research in Dr. Acevedo-Duncan's laboratory investigates signal transduction pathways involved in cell cycle control in high-grade gliomas, one of the most radioresistant forms of cancer for which there is no current successful therapy. These studies explore whether certain protein kinase C (PKC) isozymes regulate specific cell cycle phases in human glioma cells, since earlier studies have implicated elevated levels of PKC in growth control of gliomas. In particular, recent findings suggest that PKC may regulate the cell cycle through its interaction with cyclins and cyclin-dependent kinases (CDKs). Activation of the CDKs is through phosphorylation on a threonine residue by CDK-activating kinase (CAK).
To evaluate if PKC is involved in the mechanism of CAK activation, the phosphorylation of CAK and one CDK family member, cdk2, was monitored throughout the cell cycle. Results indicate that PKC inhibitors prevent hyperphosphorylation of CAK and cdk2 at specific points in the cell cycle, suggesting that PKC is involved in regulating CAK. Current studies are exploring the mechanisms of CAK regulation by PKC, for the ultimate purpose of identifying new molecular targets for development of novel therapies to treat gliomas.