Michael Ben Major, PhD

Research Interest

Metabolic Regulation

Islet Biology / Immunology

Category(ies) of Research

Basic

Descriptor of Research

My lab studies how perturbation of specific signal transduction pathways contributes to the initiation, progression and dissemination of cancer. We employ a “systems level” integrative discovery platform to characterize pathway dynamics in normal and cancer cell models. More specifically, we use mass spectrometry-based proteomics to define the protein-protein interaction and protein proximity networks, along with phosphorylation and ubiquitylation post-translational modifications. Much of our effort focuses on the WNT and NRF2/oxidative stress signaling pathway. We then annotate the nodes within the 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 tissue and various biochemical and cell biological systems. Using these technologies, a major focus of my lab is to interrogate the NRF2 signaling pathway in lung and upper aerodigestive cancers as well as a new focus on metabolic disease. We recently created a new conditionally active NRF2 mouse GEMM and surprisingly discovered new roles for NRF2 in white adipose tissue. Ongoing projects are interrogating NRF2 signaling in adipose tissue, including NRF2-driven metabolic reprogramming in human and murine experimental models.

PubMed