Project Grant R01DK148785

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Rush University Medical Center $749,087 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to investigate sodium-independent mechanisms of edema in nephrotic syndrome.

The project studies the role of circulating angiopoietin-like 4 (ANGPTL4), specifically its C-fragment, as a mediator of skin capillary endothelial permeability in nephrotic syndrome-related edema. Work includes inducing nephrotic syndrome in rodent models to quantify edema formation and developing surrogate in vitro assays using dermal endothelial cells; developing a novel ex vivo three-dimensional reconstruction method for rodent skin biopsies using microcomputed tomography; conducting x-ray crystallography to identify exposed portions of rat and human ANGPTL4-C region; developing monoclonal antibodies to selectively deplete rat ANGPTL4 C-fragment; and studying mechanisms by which C-ANGPTL4 fragments induce increased endothelial permeability in animal models and cultured dermal endothelial cells.

Performance occurs at Chicago, Illinois. The period of performance runs from September 1, 2026, through May 31, 2031. This is a Project Grant, a standard assistance type under the program that supports extramural basic and clinical biomedical research improving understanding of disease mechanisms and leading to improved prevention, diagnosis, and treatment of diabetes, digestive, and kidney diseases.