Bryce Paschal, PhD, Professor of Biochemistry and Molecular Genetics, was awarded a 5-year $2.3 million grant from the National Cancer Institute at the NIH to study the enzyme PARP7 in the context of signal transduction and gene expression pathways in prostate cancer. The project builds on recent discoveries by the Paschal lab that PARP7 modifies proteins with ADP-ribose, and that PARP7-dependent signaling is actionable with the drug RBN-2397 which is in clinical trials. In a recently funded Exploration Hypothesis Development Award for $161, 500 from the Department of Defense, Paschal will implement a nanotechnology approach to inhibit the pathway by packaging RBN-2397 in nanoparticles, and selectively targeting the nanoparticles to prostate tumor cells. The project goals of the NIH and DOD projects are complementary, since the basic science discoveries inform the translational science. Paschal hypothesizes that PARP7 could be a useful drug target in advanced prostate cancers that have little or no dependence on the androgen receptor, which has been a primary focus of therapy for decades.
Collaborators on the projects include David Wotton, PhD, Professor of Biochemistry and Molecular Genetics, and Anuradha Illendula, PhD, Assistant Professor of Research, Division of Hematology and Oncology.