Gewin’s team aims to find ways to promote kidney repair and prevent the progression of fibrosis.
Dr. Leslie Gewin, a nephrologist and researcher, has been steadily expanding her research into kidney disease since moving from Vanderbilt to WashU Medicine three years ago. Leveraging the university’s extensive resources and collaborative environment, Gewin’s work focuses on the intersection of kidney injury, metabolism, and repair.
“I’ve really been able to grow my research because of the wonderful support and collaborations at WashU,” Gewin says. This collaborative approach includes working with fellow researchers from different departments such as Brian Finck, PhD, in Nutritional Science and Obesity Medicine, as well as Gary Patti and Leah Shriver from WashU’s Department of Chemistry. These partnerships have helped establish a new Metabolism Core as part of WashU’s NIH-funded Kidney O’Brien Center for Chronic Kidney Disease, which is expanding resources and metabolic assays for the nephrology research community across the country.
Research Focus
Gewin’s research is focused primarily on how metabolic processes impact the kidney’s response to injury, particularly in relation to fibrosis, or scar tissue formation. “Fibrosis essentially means the kidney loses its function, leading patients to dialysis or kidney transplant,” Gewin explains. Her team aims to find ways to promote kidney repair and prevent the progression of fibrosis.
Chronic kidney disease affects almost 15% of the US population, but exciting new drugs including SGLT2 inhibitors (e.g. Jardiance, Farxiga) can slow down the progression of kidney disease. Gewin’s team is working to understand how metabolic changes in the kidney tubules, the most vulnerable to injury, may promote either repair or further injury. “Understanding how the metabolic changes affect the injured tubules may provide insights into how SGLT2 inhibitors work and new targets for treatment of chronic kidney disease,” she notes.
Gewin’s passion for kidney research began in medical school, inspired by nephrologist Dr. David Warnock at the University of Alabama. Initially intimidated by the complexity of kidney function, she eventually found it fascinating.
Patients with kidney disease patients are often very sick, and understanding kidney physiology empowered me to feel comfortable treating these patients
Gewin
Journal of Clinical Investigation Work
Gewin’s recent work involves a collaboration with Irfan Lodhi, Ph.D., from the Division of Endocrinology, that was published in JCI Insight focused on fatty acid metabolism in kidney tubules. Much attention focuses on how the mitochondria, the powerhouses of the cell, metabolize fatty acids in tubules. Her group genetically deleted a key mitochondrial enzyme involved in fatty acid metabolism, expecting a worse response to aging and chronic injury. However, the results were surprising—mice displayed only subtle changes, suggesting redundant metabolic pathways were compensating.
“The human body is resilient, and understanding how the kidney adjusts to injury can help with new treatments,” Gewin says. In collaboration with Dr. Lodhi, she is now investigating the role of peroxisomes in metabolizing fatty acids in healthy and injured kidney tubules. Her postdoctoral fellows Dr. Safaa Hammoud, PhD, led the work in JCI Insight, and Dr. Kevin Hurtado, PhD, will be studying peroxisomes and kidney metabolism.
Gewin’s work reflects her commitment to both research and patient care, with the goal of ultimately improving outcomes for patients with chronic kidney disease. By exploring how metabolism influences kidney repair and fibrosis, Gewin hopes her findings will lead to new therapeutic strategies and a deeper understanding of kidney health.
