The ASPIRE Path in Molecular Medicine

I will be investigating the cellular mechanisms of GLP-1 receptor agonism on micro- and macro-vascular endothelial dysfunction in sepsis. I am particularly interested in understanding liraglutide’s (GLP-1 agonist) underlying mechanisms of action on promoting lung endothelial anti-inflammatory, antioxidant, and cell repair effects during sepsis injury. Through these mechanisms, I believe that liraglutide will limit microvascular permeability during sepsis. We will use a murine model of polymicrobial sepsis and in vitro models of microvascular endothelium to study the effects of liraglutide on organ specific microvascular injury. To test whether liraglutide has direct endothelial protective effects, we will use primary human large and small vessel endothelial cells treated with lipopolysaccharide (LPS) with and without liraglutide and measure barrier function, permeability, injury, and activation. Additionally, I aim to quantify GLP-1R expression in the lungs, kidney, liver, heart, and brain in patients who died with sepsis. We will leverage the Vanderbilt Synthetic Derivative and Path-Link to generate tissue microarrays of lung, kidney, liver, heart, and brain from patients who died from sepsis and a control group of age and sex matched controls who died without sepsis. I hope to gain experience in applied aspects of biomedical research and hope to build connections with clinicians.