The major effort in the lab is directed towards investigating how tumor-specific dysregulation of the pRB signaling pathway affects downstream gene expression and the cellular response to DNA damage. Four projects are currently underway. First, we are utilizing a modified chromatin immunoprecipitation approach to capture and identify genomic DNA target sequences conditionally associated with pRB-containing complexes recovered from intact chromatin in untransformed primary human cells. Second, we are investigating functional heterogeneity amongst closely related components in the pRB pathway. Specifically, we are conducting comparative analyses of the INK4 proteins p16INK4a and p18INK4c and their preferred target kinases, the cyclin dependent kinases cdk4 and cdk6. Third, in collaboration with Dr. Jeff Marks, we are developing a mammary gland organoid approach to quantitate and analyze parity-dependent DNA damage checkpoint responses in the context of the primary human mammary tissue. Finally, we are engaged in a collaborative effort with Dr. Francis Ali-Osman to investigate the role of the glutathione-S-transferase protein P1 (GSTP1) in conferring chemotherapeutic drug resistance in human gliomas.
