Ongoing Research Projects
We are inspired by the powerful influence of molecular metabolism on cell function and fate. Our purpose is to study this in pancreatic beta cells and local immune cells in health, obesity and diabetes. We have identified metabolic pathways which protect against inflammation associated with metabolic disease. At the moment, we are contemplating how these pathways shape the metabolic milieu of pancreatic islets and local immune cell activities which is an unexplored scientific area. Our lab has developed a new system and uses technologies such as metabolomics, proteomics and transcriptomics to investigate these questions.
Profile and then engineer the metabolic milieu of pancreatic islets in health and diabetes contexts
Glucose fuels urea cycle and de novo glutathione synthesis to enhance beta cell stress defense.
Identify molecular metabolic features that improve stem cell derived beta cell survival and engraftment in vivo in islet transplantations
Strategy to identify metabolites in beta cell communication with macrophages in vitro. Islet metabolite changes are correlated with effects on macrophage activation.
Provide a molecular explanation of how inflammation engages beta cell metabolism and which components lead to cytotoxicity
Integrated network analysis to identify molecular metabolic and signaling pathways that coordinate inflammation-dependent beta cell death via nitrogen (NH4+) build-up. Urea cycle and ARG2 activity remove NH4+ and prevent cell death. Scenario of ARG2KO shown below in orange box will distill top pathways of NH4+-dependent cell death.
