“Ultimately, this project will lay groundwork for new clinical tests and drugs for organ failure in sepsis and other severe inflammatory responses that occur with infections.”
-Ethan Anderson

The National Institutes of Health has awarded University of Iowa (UI) College of Pharmacy Associate Professor Ethan Anderson a four-year, $1.7 million grant through its National Heart, Lung, and Blood Institute to study sepsis. As primary investigator, his project will examine the metabolic effects of a protein released by the liver during sepsis and perform tests on this protein in blood samples from patients with sepsis.

Sepsis is a dangerous whole-body response to infection or trauma that often leads to death due to overwhelming inflammatory and metabolic stress in critical organs such as the heart, lungs, and kidneys. According to the Centers for Disease Control and Prevention, at least 1.7 million adults in the United States develop sepsis each year, with nearly 350,000 dying as a result.

“My research team is very excited about this grant and eager to begin work on this project,” said Anderson. “What we have come to find out from our ongoing research, much of which has been funded by the American Heart Association, is that an abundant mitochondrial protein called PHB1 (and possibly other members of its family) do not simply ‘stay put’ inside of cells, but may be released by cells and traffic throughout the body as a signal between organs to control metabolism and inflammation in distant sites. This has ramifications not just for sepsis but other metabolic diseases, particularly diabetes and cancer. Some recent studies suggest that PHBs may have important roles in these other diseases, so who knows where this project may take us.”

Co-investigators are David Roman, UI College of Pharmacy associate dean for Research and Graduate Education, and Ryan Boudreau, associate professor of Internal Medicine-Cardiovascular Medicine at the UI Carver College of Medicine. The team also is collaborating with critical-care physician-scientist Matt Rondina from the University of Utah.

“The investigators have distinct yet complementary expertise. It’s a highly collaborative project with potential to move the needle in drug discovery,” said Jonathan Doorn, UI College of Pharmacy John L. & Carol E. Lach Chair in Drug Delivery Technology. “I am thrilled about this project. The scholarship to be pursued is both elegant and innovative and has potential to catalyze the development of new therapies and improved clinical tests aimed at sepsis or inflammatory related damage.”

For this project, Anderson’s team will use genetically modified mice and clinically relevant mouse models of sepsis. They will also study blood samples from critically ill patients with sepsis from the Health University of Utah and UI Hospitals & Clinics.

“Ultimately, this project will lay groundwork for new clinical tests and drugs for organ failure in sepsis and other severe inflammatory responses that occur with infections,” said Anderson. “As we saw during COVID, where many patients died as a result of respiratory failure caused by severe inflammatory stress, new therapies and tests are urgently needed in this space.”