Phenotypic diversity in BPH. Left: glandular enlargement. Middle: Stromal enlargement. Right: Mixed type. We believe that the basis for heterogeneous clinical responses in BPH is pathologic diversity. There are a number of phenotypes evident across and even within patients. In one area, a patient can display a stromal tumor while the other area display an epithelial nodule.
Our goal is to provide a rational basis for therapeutically treating these individual phenotypes by dissecting them macroscopically and then comparing their cell-specific molecular profiles to reduce the noise of cellular heterogeneity and inflammation. Our first goal is to identify a cell or cells of origin for the varying phenotypes by phenotyping the tissues with single cell RNA sequencing. This includes a comprehensive evaluation of the immune and inflammatory infiltrate as well as fluctuations in epithelial and stromal subpopulations.
We are subsequently isolating the cell types of interest and performing molecular profiling. Based on these targets, we will use our mouse and cell culture models to experimentally test our hypotheses.