Naomi Hamburg, MD, MS

Institution: Boston University
Research: Endothelial Phenotype in Cardiometabolic Disease
Categories: BU

The Hamburg laboratory focuses on understanding the development and clinical relevance of vascular dysfunction in patients with type 2 diabetes and obesity. The lab uses translational research approaches that combine the measurement of vascular function in patients with characterization of endothelial phenotype at the cellular level to identify pathways that have potential to protect the vasculature from the accelerated aging induced by metabolic diseases. At present three projects are ongoing:

1) Mechanisms of endothelial dysfunction in patients with type 2 diabetes and obesity. Patients with type 2 diabetes experience accelerated vascular aging, premature atherosclerotic cardiovascular disease, and increased cardiovascular risk. Alterations in endothelial function promote atherosclerotic development in type 2 diabetes. We have identified signaling pathways that promote inflammation, oxidative stress and mitochondrial dysfunction in endothelial cells isolated from patients with type 2 diabetes. Using isolated endothelial cells, we have demonstrated several novel targets and therapies that may improve nitric oxide bioavailability. We have developed approaches to characterize coding and non-coding RNA in endothelial cells from patients with diabetes and are relating to measures of vascular aging to identify their functional relevance.

2) Mechanisms linking novel therapies for type 2 diabetes with vascular protection. Considerable enthusiasm exists for newer agents including GLP-1 agonists and SGLT2 inhibitors in reducing cardiovascular events in type 2 diabetes. Improvement of endothelial cell signaling and phenotype may serve as a marker for novel therapeutic interventions to improve cardiovascular health. We are conducting clinical intervention studies to evaluate whether novel diabetes medications will restore endothelial cell non-coding RNA expression and function.

3) ER stress and mitochondrial function in the obesity and diabetes. Metabolic stressors including elevated glucose and obesity impact endothelial cell metabolism characterized by ER stress and increased mitochondrial oxidative stress. We are evaluating the impact of therapies targeted at reducing ER stress and restoring mitochondrial health on vascular function in patients with diabetes.