Lower urinary tract symptoms (LUTS), including filling and voiding symptoms, affect approximately 40% of older men. Symptoms have diverse etiologies, but in many instances they are linked to benign prostatic hyperplasia (BPH). The etiology of BPH itself is poorly understood. While BPH is approached clinically as a single disease, there is likely molecular heterogeneity in the drivers leading to the disease. Indeed, BPH demonstrates diverse histologic patterns, is associated with a spectrum of LUTS, and has varied responses to therapy. New high-throughput sequencing tools can provide insight into both the molecular diversity of BPH and potential new targets for treatment.
We hypothesize that BPH is a heterogeneous disease, and that large-scale molecular profiling will lead to a better understanding of pathogenesis, and a refined classification for improved biomarkers and symptom management. Transcriptome analysis can identify clinically meaningful subtypes of BPH with distinct driver pathways. We can test the functional significance of identified driver pathways in BPH by developing new cell culture models. Here, we bring together a team with expertise in urology, pathology, genomics, microbiomics and cell culture models, to develop a robust molecular classification of BPH.
Aim 1: Determine a robust transcriptional classification of BPH using RNA-seq.
We are carrying out next-generation transcriptional profiling (RNA-seq) of BPH tissue specimens and matched normal prostate. Data are being analyzed to identify molecular subtypes, LUTS-associated signatures, underlying signaling pathways, and molecular targets. We are also investigating BPH-associated non-coding RNAs and microbiomes.
Aim 2: Develop cell culture models of BPH to investigate BPH biology.
We are exploring varied approaches, including conditional reprogramming (ROCK inhibition), to generate new cell culture models of BPH. Genetic and pharmacologic tools will then be used to investigate newly-identified candidate genes and pathways involved in BPH pathogenesis.