What makes us the way we are? Why are some people predisposed to be overweight? How is it that some of us are prone to Type 2 diabetes?
Research projects in the Alejandro lab are aimed to understand the developmental origins of metabolic dysfunction in insulin resistance, obesity, and type 2 diabetes. We are interested in understanding the early life origins of insulin-producing beta-cell dysfunction and to identify novel endogenous modulators of insulin secretion and regeneration for potential treatment for both type 1 and type 2 diabetes. We use both human samples and genetic animal models to assess the roles of key nutrient-sensor proteins like mTOR and OGT in the programming of multiple tissues setpoints during the developmental period that can impact their function and eventual development of insulin resistance, obesity, and diabetes in adulthood. Identifying modifiable risk factors is key in decreasing the incidence of metabolic dysfunction/inflammation in obesity and type 2 diabetes.
The long-term research goal of the Alejandro Lab is to stop the vicious cycle of diabetes by launching a multi-pronged research program.
One research objectives of the lab is to understand how placental-insufficiency induced by multiple factors (maternal obesity, diabetes, or preeclampsia) during pregnancy alters the adult offspring's beta-cell function and susceptibility to diabetes and to identify the mechanistic link between beta-cell programming and sensitivity to cellular stress involving ER stress, oxidative stress, autophagy and mitochondrial stress in chronic hyperglycemia and hyperlipidemia conditions. A second objective involves studying the roles of mTOR and OGT in beta-cell development, function, and regeneration. We use a diverse range of techniques from epigenetics, electrophysiology, biochemistry, molecular approaches in vitro to whole animal in vivo phenotyping of glucose metabolism and beta-cell function.