PhD Thesis Defense: Han Zhang

Han Zhang, Pharmsci graduate student (Ricke Lab), will be defending his PhD research thesis:

Characterization and Regulation of Androgen Receptor Signaling in Prostatic Diseases

Abstract:
The prostate is an androgen-responsive gland whose development, maintenance, and function are tightly regulated by androgen receptor (AR) signaling. AR is a ligand-activated nuclear receptor that functions as a transcription factor, controlling gene expression essential for prostate epithelial differentiation, secretory function, and tissue homeostasis. AR is activated when androgens such as testosterone or dihydrotestosterone (DHT) bind to the receptor, triggering conformational changes that promote AR dimerization, nuclear translocation, and binding to androgen response elements (AREs) in target gene promoters. Through this process, AR regulates a wide range of biological pathways, including cellular proliferation, differentiation, metabolism, and survival.

While AR signaling is essential for normal prostate physiology, dysregulation of this pathway contributes to the development and progression of several prostatic diseases. Two of the most prevalent conditions affecting the aging male population are benign prostatic hyperplasia (BPH) and prostate cancer (PC). BPH is characterized by nonmalignant enlargement of the prostate that results from excessive proliferation of epithelial and stromal cells, leading to urinary obstruction and lower urinary tract symptoms (LUTS). In contrast, PC represents one of the most common malignancies among men worldwide and is a leading cause of cancer-related mortality. Despite their distinct pathological outcomes, both diseases share AR signaling as a central molecular driver.

Here, we characterize multiple layers of AR regulation, including transcriptional signaling networks, RNA-mediated regulation, cellular stress responses, and age-related tissue changes. Together, these studies aim to provide new insights into the molecular mechanisms underlying prostate disease development and therapeutic resistance.