Paschal Lab
Principal Investigator: Bryce Paschal
Institution: University of Virginia (Charlottesville, VA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: ✅ Accepting PhD Students
Research Focus
PROJECT SUMMARY This proposal builds upon our discovery in the previous funding period of a novel pathway in prostate cancer cells that integrates androgen signaling with ADP-ribosylation. The pathway has four key components, the androgen receptor (AR), Parp7, Parp9 and Dtx3L. We found that the pathway involves AR induction of Parp7 and multi-site mono-ADP-ribosylation by Parp7, on cysteines in the AR amino-terminal domain. In this pathway, Parp7 acts as an ADP-ribose writer and Parp9 serves as an ADP-ribose reader, and the outcome of these reactions is androgen- dependent assembly of an AR-Dtx3L/Parp9 complex and regulation of AR activity as a transcription factor. With this knowledge base, we are positioned to tackle important questions on how the pathway drives biological effects in prostate cancer cells, and whether Parp7 is an actionable target in models that include castrate-resistant prostate cancer where there is an unmet clinical need. In Aim 1, we will determine how the AR-Parp7 pathway and mono-ADP- ribosylation regulate tumorigenesis in prostate cancer cells using structure-function experiments that interrogate the contributions of each of the four components. Since AR…
Active NIH Awards
- 5R01CA214872-09: Parp Function in Prostate Cancer (2026)
- 5R01CA214872-08: Parp Function in Prostate Cancer (2025)
- 5R01CA214872-07: Parp Function in Prostate Cancer (2024)
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