Michael J. Weber, PhD
Signal transduction by serine/threonine kinases
The Weber laboratory utilizes tools of cell biology, protein chemistry and molecular biology to understand how signal transduction pathways control cell growth and apoptosis and how these controls are altered in cancer. A major focus of this research is on the MAP Kinase cascade, a ubiquitous signaling pathway that generates specific biological outcomes dependent on biological context. Recent findings of the lab have demonstrated an important role for "scaffolding proteins" that assemble components of the signaling cascades. They recently discovered the MORG1 scaffold protein (MAP Kinase Organizer) that regulates responses to LPA but not EGF. Signaling scaffolds can control the location, regulation, timing, substrates, biological functions, and suitability for therapeutic intervention of a signaling pathway. This research made use of the Biostatistics Core, to help evaluate multi-factorial responses to mitogens, and the Mass Spec and DNA cores for molecular and proteomic analysis.
The lab pioneered the use of phosphorylation-site specific antibodies to probe archival paraffin-embedded pathology specimens, and discovered that the MAP Kinase cascade was activated in prostate cancer. Activation of this pathway is sufficient for and can be necessary for progression of prostate cancer to an androgen-independent disease. Therefore the Ras-MAP Kinase pathway is an attractive target for therapy of advanced prostate cancer. Current research aims to determine how to select combinations of therapies in cancer treatment.