Michael Major, PhD

Alan A. and Edith L. Wolff Professor of Cell Biology and Physiology

Washington University in St. Louis (WU)

My lab studies how perturbation of specific signal transduction pathways contributes to the initiation and progression of cancer. We employ a “systems level” integrative discovery platform to characterize pathway dynamics in normal and disease cell models. Mass spectrometry-based proteomics is used to define the protein-protein interaction and protein proximity networks, along with phosphorylation and ubiquitylation post-translational modifications. We then annotate the physical networks for function, as determined by established and novel functional genomic screening technologies. Integration of these data with disease-associated mutation and gene expression data yields a powerful tool for discovery—a disease annotated physical/functional map. Critical to our success is the development and implementation of computational scoring algorithms, relational database construction and data visualization. Ultimately, the models and hypotheses produced are challenged through mechanistic studies employing cultured cancer cells, new and established mouse models, clinical biopsies and various biochemical and cell biological systems.