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Characterization of Angrogen-Responsive Protein Networks Characterization of Androgen Reponsive Kinase Cascades |
Primary Research Focus The Wright Lab's primary research goal is to elucidate Androgen Receptor function during the initiation and progression of prostate disease in men. Characterization of Androgen Co-Regulated Protein Networks in Prostate Epithelial Cells The laboratory is defining how androgens influence the growth and differentiation of diseased human prostate epithelial cells. Large-scale quantitative protein profiling methods are being used to characterize co-regulated protein pathways in various human prostate epithelial cell lines and tissues. Characterization of Androgen-Reponsive Kinase Cascades Androgen-responsive protein kinase cascades are poorly characterized during different stages of prostate disease. However, protein kinase pathway are critical mediators of cell growth in many human diseases. Our laboratory has recently identified a group of androgen-responsive protein kinases that modulate the growth and differentiation of human prostate epithelial cell lines in vitro. This subgroup of kinases and their target phosphorylated substrates are being characterized in different human prostate epithelial cell lines. Characterization of Androgen Receptor Interacting Protein Modules Androgens cause AR to move out of the cytoplasm and into the nucleus where it binds to targeted genes to modulate their expression in normal and diseased prostate epithelial cells. Although many components of this nuclear transformation process have been characterized, not all steps in AR migration into the nucleus and modulation of transcription are fully characterized. The laboratory is systematically characterizing proteins that bind to AR prior, during, and after its release from androgenic hormones using quantitative mass spectrometry methods.  Systematic analysis of AR function on the macro and micro-level will provide a robust architecture for understanding AR complex roles during different stages of prostate epithelial disease in men. Developing epithelial protein expression libraries Securing sufficient amounts of diseased human tissue to interrogate protein expression patterns in clinically relevant samples poses a serious limitation in the development of robust protein biomarkers of diagnostic, prognostic, or therapeutic value to different human diseases. Thus, our group is using a strategy called the Direct Tissue Proteomics (DTP) to identify proteins in formalin-fixed paraffin embedded tissues using shotgun proteomics methods via tandem mass spectrometry (MS/MS). The identification and validation of novel protein biomarkers will play an important role in treating life-threatening epithelial diseases. 1. Overview of Prostate disease progression. Cells become increasingly unorganized as the disease progresses toward metastasis. T1 and T2, highlighted in blue, are described as "non-significant" prostate cancer, meaning that the disease is still located within the prostatic capsule and is highly curable. T3 and T4, highlighted in orange, are described as "significant" prostate cancer, meaning the disease has metastasized outside of the prostatic capsule and is less curable.
2. The DTP method is used to create protein expression libraries unique to each stage of disease.  |
