Henrique Serezani, PhD, associate professor of Medicine in the Division of Infectious Diseases at Vanderbilt University Medical Center, has been awarded a five-year, $3 million research grant from the National Institutes of Health (NIH) to investigate the relationship between hyperglycemia and increased severity of responses to infections.
“Our research seeks to understand how altered metabolism in diabetes intersects with epigenetic modifications, affecting inflammation and sepsis,” Serezani said. “This could lead to the development of new therapeutics to reduce chronic low-grade inflammation in diabetes and improve outcomes for systemic infections.”
The project builds on previous findings that chronic hyperglycemia is linked to systemic inflammation, which may underlie several comorbidities in diabetes. In previous research, Serezani’s team found that the lipid mediator leukotriene B4 (LTB4), and by implication its high-affinity receptor BLT1, play critical roles in this process.
The new study has two main objectives: define the mechanisms promoting sustained aberrant BLT1 activation and inflammation during sepsis; and delineate the consequences of exaggerated LTB4–BLT1 signaling in driving a “cytokine storm,” organ injury, and mortality in septic humans and mice with diabetes.
People with diabetes are more susceptible to inflammatory morbidities associated with sepsis. Exploring the cellular targets involved in this enhanced susceptibility, Serezani aims to define the role of hyperglycemia in promoting epigenetic and immunometabolic mechanisms that dysregulate molecular checkpoints and promote a detrimental host inflammatory response during sepsis. Findings from this study could have implications for both basic and translational research, potentially leading to improved treatments for systemic infections in patients with diabetes.
The research is supported by NIH grant R01AI180777.