“Development and Validation of Novel Small Molecule Inhibitors for the HIRA/H3.3 Pathway in Castration-Resistant Prostate Cancer”
Principal Investigator: Dr. David A. Ostrov
Affiliation: Department of Pathology, Immunology and Laboratory Medicine
Time Period affiliated with this project: November 2024 – Present
Collaborators:
Dr. Alexander M. Ishov, Department of Anatomy and Cell Biology, UF College of Medicine
Ariyana Aboutaleb-Kermani, M.S., Department of Anatomy and Cell Biology, UF College of Medicine
Research Responsibilities
• Supporting high-throughput virtual screening of 139,735 compounds from the NCI Developmental Therapeutics Program.
• Utilizing molecular docking tools (AutoDock Vina) and parallel AI processing on HiPerGator to identify high-affinity binders for the UBN1/H3.3 interface.
• Supporting compound selection, scoring, and validation using assays such as AlamarBlue and immunofluorescence microscopy.
• Participating in cross-departmental collaboration and synthesis of findings for academic dissemination.
RESEARCH
Prostate cancer is one of the most prevalent malignancies affecting men worldwide. Among its forms, castration-resistant prostate cancer (CRPC) poses one of the greatest therapeutic challenges due to its ability to bypass androgen receptor blockade by utilizing the glucocorticoid receptor for tumor progression. Progression to metastatic CRPC (mCRPC) is associated with poor prognosis, limited treatment options, and increased morbidity.
Our research seeks to develop novel small-molecule inhibitors that target the HIRA/H3.3 pathway, specifically aiming to disrupt the interaction between UBN1 and H3.3 within the chromatin assembly complex.
Research Focus