Welcome to the Lazarus Lab, a new chemical biology research group at the Icahn School of Medicine at Mount Sinai.
Our lab is looking at how cells respond to nutrient changes and how we can exploit these mechanisms in human diseases including cancer and diabetes. Our approach is a multidisciplinary one that uses biochemistry, x-ray crystallography, and pharmacology to study these systems.
We are interested in two main areas that respond to nutrient status. The first is a pathway called autophagy, a conserved process whereby cellular components are degraded for energy, building blocks, and quality control. We are interested in developing tools to modulate autophagy in cells, and in evaluating autophagy inhibition as a therapeutic strategy for cancer. We have developed small molecule inhibitors of kinases that control this pathway.
The second area we are focused on is the unusual nutrient-sensing glycosyltransferase O-GlcNAc Transferase (OGT). This enzyme responds to levels of glucose and other nutrients by dynamically glycosylating cellular signaling components and epigenetic modulating enzymes. This single enzyme glycosylates over 1,000 nucleocytoplasmic substrates through unknown mechanisms. We are interested in using biochemical and crystallographic approaches to understand the mechanisms that link glucose levels and epigenetic regulation.