Congratulations to two of our WashU Nephrology investigators who recently received career development awards.
Eirini Kefalogianni, PhD, Instructor in Medicine, recently received a three-year, $231,000 (total), Career Development Award from the American Heart Association (AHA) to study the roles of cellular and circulating Tumor-Necrosis-Factor-Receptors 1 and 2 (TNFR1/2) in kidney disease. Her application was ranked at 0.21 percentile, ranking among the very best!
Circulating TNFR1/2 are significant predictors of the severity and progression of kidney disease of different diagnosis. It is still unknown what the cellular TNFR1 or TNFR2 pathways individually contribute to kidney injury or disease progression and whether TNFR1/2 circulating in serum are causally involved and could be therapeutically modulated.
“The major goal of this project is to characterize the roles of these receptors in kidney injury, inflammation and fibrosis using mouse models of disease,” says Kefalogianni. “Unique pharmacological and genetic tools that we developed, or that are now available, will allow us to dissect the individual components of membrane and circulating TNFR1 and TNFR2 and identify their roles in kidney disease and progression to fibrosis.”
Identification of a specific TNFR1- or TNFR2-dependent pathway as key for slowing down or for accelerating kidney disease progression will allow for a more sensible design of treatment regiments with reduced side effects.
The AHA Career Development awards are given to promising investigators to support training and development to enhance future success as independent research scientists. While in the Herrlich Laboratory, Kefalogianni has been studying the mechanisms involved in kidney fibrosis and, most recently, was first-author of the 2019 publication, “Proximal Tubule-Derived Amphiregulin Amplifies and Integrates Profibrotic EGF Receptor Signals in Kidney Fibrosis,” in the Journal of the American Society of Nephrology.
Monica Chang-Panesso, MD, assistant professor of medicine, received a five year, $752,858 (total), K08 Mentored Clinical Scientist Research Career Development Award to study tubular senescence and proliferative capacity of the aging kidney. Her grant submission received a perfect score of “10”!
Acute kidney injury (AKI) and chronic kidney disease (CKD) are much more common among the elderly, and the aging population in the United States is rising rapidly. By 2030, about one in every five Americans will be 65 and older; this is more than twice their number in 2000.
The purpose of Chang-Panesso’s research is to explore the mechanisms underlying the decreased repair response in aging kidney after injury, with a specific focus on the role of tubular senescence and decreased proliferative capacity as a possible driver of failed repair.
“Gaining insight into the cause for lack of reparative capacity in the aging kidney will point the way towards new therapeutic targets and interventions for this critically important clinical problem,” says Chang-Panesso.
The funding, together with the mentorship of Dr. Benjamin Humphreys, chief of the Division of Nephrology, will further Chang-Panesso’s goal of becoming an independent physician-scientist. As part of the Humphreys Lab, Chang-Panesso has already been part of major research in our division, most recently as first-author of the 2019 publication, “FOXM1 Drives Proximal Tubule Proliferation During Repair from Acute Ischemic Kidney Injury,”inThe Journal of Clinical Investigation (Kefalogianni was also a co-author of this publication).
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