Research Focus

Androgen Signaling Networks in Androgen Receptor-Related Human Diseases

We are studying the molecular and cellular actions of androgen signaling pathways in normal and diseased organs/tissues. A major goal of the laboratory is to build quantitative models of androgen-mediated signaling networks that accurately predicts the non-genomic ( i.e. membrane-initiated steroid signaling, or MISS) and genomic actions of AR at the molecular and cellular level. Model systems will guide our understanding of how androgenic hormones impact molecular and cellular responses in cells, organs, and tissues. However these systems will also provide a molecular roadmap for targeting and modulating androgen signaling networks in AR-related diseases that afflict prostate epithelial cells, skeletal muscle cells, and neurons (e.g. prostate cancer and spinal bulbar muscular dystrophy).

Several on-going laboratory projects are listed below:

• Molecular analysis of AR-interacting protein complexes.

• Molecular analysis of androgen-mediated phosphorylation cascades.

• Molecular analysis of androgen-responsive networks.

• Molecular analysis of AR transcriptional complexes.

Molecular characterization of these androgen signaling pathways will provide an integrative understanding of AR-mediated actions at the molecular and cellular level. These findings will offer opportunities to identify missing molecular links in disparate signal-transduction pathways to provide novel biochemical insights into the connectivity of androgen signaling networks. This information will also provide a robust framework for testing and predicting androgenic responses in normal and diseased systems. We plan to build predictive models of androgen-mediated signaling networks that define aberrant AR functions in prostate cancer and spinal bulbar muscular atrophy. We also anticipate these findings will help us understand how androgen signaling networks contribute to unidentified androgen-related pathologies in the human body.

Tissue Proteomics: Validation of Biomarkers in Human Prostate Cancer

Our group is also validating biomarkers in clinical prostate samples. We are using targeted MS workflows to quantify tissue biomarkers in radical proctectomy samples. Our goal is to characterize biomarkers to indolent and lethal forms of prostate cancer. These studies have the potential to define diagnostic, prognostic, and therapeutic biomarkers in the management and treatment of high-risk, organ-confined prostate cancers and early-stage, metastatic prostate cancers.