Gryder Lab
Principal Investigator: Berkley E Gryder
Institution: Case Western Reserve University (Cleveland, OH)
Primary Subfield: Genetics/Genomics
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
ABSTRACT Nuclear receptors are steroid-dependent transcription factors that confer cell identity and function. They guide development, and maintain homeostasis in adult tissue, such as the testosterone responsive Androgen Receptor which governs male-specific organs and phenotypes. Aberrant AR-driven gene expression programs give rise to prostate cancer. When resistance arises after androgen-deprivation therapy (ADT) the disease advances to the much more lethal metastatic castration-resistant prostate cancer (mCRPC), often becoming resistant to ADT by overexpressing AR. New evidence suggests that many other transcription factors and epigenetic co-activator proteins may create disease-specific enhancers with the AR to drive tumors, especially in treatment-relapsed mCRPC. By harnessing sophisticated molecular biology and computational biology techniques, we will map the epigenetic mechanisms at work in mCRPC, in clinically relevant PDX models and cell lines with epigenomes closely matching mCRPC tumors. We will show how to stop the AR-axis using small molecules (AR in verse agonists, ARIAs) we designed, synthesized and developed with novel mechanisms of action, where the AR undergoes…
Active NIH Awards
- 4R01CA291963-03: Mechanisms of Androgen Receptor Inverse Agonists in Advanced Prostate Cancer (2026)
- 5R01CA291963-02: Mechanisms of Androgen Receptor Inverse Agonists in Advanced Prostate Cancer (2025)
- 1R01CA291963-01: Mechanisms of Androgen Receptor Inverse Agonists in Advanced Prostate Cancer (2024)
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