Harvard Catalyst Profiles

Over 90% of adult males develop lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction by age 80, rendering benign prostatic hyperplasia (BPH) the most common proliferative abnormality in humans. BPH negatively impact the quality of life of 210 million men globally, accounting for significant life years lost, and costing the US healthcare system >$4 billion per year. Medical therapy for BPH, which includes 5α reductase inhibitors (5ARI, i.e., finasteride) targets both stromal and epithelial cells in the prostate gland. 5ARI’s are the only class of BPH-related drugs that reduces prostate size for the alleviation of LUTS. However, 34% of BPH patients do not respond to treatment and resistance to 5ARI therapy is a major limiting factor for effective management of BPH. It is not yet possible to predict responders vs. non-responders to 5ARI therapy, which creates a significant gap in our ability to effectively manage these patients. Finasteride, the most commonly prescribed 5ARI, is an inhibitor of steroid reductase 5α-2 (SRD5A2; also known as: 5-alpha reductase type 2 (5-AR2)), which is encoded by the gene SRD5A2. This proposal is based on the premise that epigenetic changes to SRD5A2 account for the significant number of patients who are unresponsive to 5ARI therapy. Here, we hypothesize that absence of SRD5A2 in human prostatic tissue, due to somatic methylation, is directly responsible for lack of sensitivity to 5ARI therapy in patients with BPH. Our goal is to assess SRD5A2 methylation and expression as a gene signature to predict which patients will respond to 5ARI therapy.

The student's role will be to explore the molecular and hormonal pathways and help develop a non-invasive radiologic signature to determine signatures of resistance to BPH-related therapies.

We have hosted students with varying degrees of experience and happy to consider any student who is motivated and excited about pursuing a scientific and clinically relevant question.