The Wright Laboratory is focused on defining the composition, activity, and overall cellular function of protein complexes in higher organisms. We utilize quantitative mass spectrometry as a platform to study protein network dynamics in model experimental systems.
Mapping Androgen Receptor Signaling Networks in Androgen Receptor-Related Diseases
We are delineating androgen signaling cascades in hormone-responsive systems with the goal of understanding how aberrant androgen receptor (AR) signaling contributes to the development and progression of the AR-related diseases in human prostate cancer (CaP) and spinal bulbar muscular atrophy (SBMA). The laboratory uses model experimental systems of CaP (e.g. neoplastic prostate epithelial cells) and SBMA (e.g. skeletal muscle, neurons) to dissect androgen signaling pathways at the molecular and cellular level. We are currently interrogating androgen receptor signaling networks on three biochemical levels. They include mapping AR-interacting protein complexes, defining androgen-mediated phosphorylation cascades, and defining androgen-responsive protein networks. These studies will define cell-type and tissue-selective actions of androgens and AR signaling pathways in CaP and SBMA. Furthermore, the biochemical relationships between these pathways will be examined to determine if these pathways act individually or synergistically to influence aberrant AR signaling in CaP and SBMA. Our long-term goal is to provide the biomedical research community an integrated molecular framework for developing and testing new hypotheses of how aberrant androgen receptor signaling contributes to the evolution and progression of AR-related diseases.
Defining Molecular Biomarkers in Androgen Receptor-Related Diseases
The Wright laboratory is also identifying protein biomarkers in clinical tissue samples of CaP. We are using both directed and targeted mass spectrometry workflows to identify and quantify tissue biomarkers in radical prostatectomy samples. The goal of this research is to characterize biomarkers to indolent (e.g. organ-confined) and lethal (e.g. metastatic) forms of CaP. These studies have the potential to define novel diagnostic, prognostic, and therapeutic biomarkers in the management and treatment of high-risk, organ-confined CaP and early-stage, metastatic CaP. We are also developing better proteomic workflows to validate tissue biomarkers in plasma and serum using mass spectrometry-based assays.