Chronic renal disease impacts around 37 million individuals in the U.S., and for a significant number, a remedy remains elusive. However, a novel research initiative at Washington University in St. Louis aims to transform this by revealing the mechanical foundations of kidney cell damage.
To confront chronic renal disease, Guy Genin, the Harold and Kathleen Faught Professor of Mechanical Engineering at the WashU McKelvey School of Engineering, alongside Jeffrey Miner, the Eduardo and Judith Slatopolsky Professor of Medicine in Nephrology at WashU Medicine, joined forces with Hani Suleiman, an assistant professor of medicine at the University of Texas Southwestern Medical Center. This cross-disciplinary group, embodying proficiency in medicine, cell biology, genetics, and engineering, was awarded a five-year $4 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH).
With NIH’s backing, the team intends to investigate the mechanobiology of podocytes, distinct cells within the kidney that assist in blood filtration.
“Podocytes resemble octopuses that are embracing their neighbors,” remarked Genin, who also serves as co-director of the National Science Foundation Science and Technology Center for Engineering Mechanobiology (CEMB). “By examining these extensions using advanced microscopy, the ways they converge to establish the kidney’s filtration system become evident. If these connections are disrupted, the whole filtration apparatus collapses. Everyone is born with a specified number of podocytes. You gradually lose some, including several each time you urinate, but certain illnesses and harm to the kidneys can lead to accelerated loss.”
The team aspires to assist individuals in retaining more podocytes for an extended period, postponing the onset of renal dysfunction. Their primary focus is on Alport syndrome, a genetic condition causing podocyte damage, which results in diminished kidney function that does not recover. The team theorizes that injury and the capacity for recovery are intimately linked to podocytes’ mechanobiology, or how these cells detect and react to mechanical forces, including those that may alter podocytes’ structure and make them detach from the kidney’s filtration barrier.
“We’re thrilled to utilize pioneering mechanobiology methods to investigate this significant illness that presently has no targeted treatments,” stated Miner, a global authority on Alport syndrome. “By revealing the mechanical underpinnings of podocyte injury, we aim to acquire knowledge that could pave the way for innovative therapies.”
This project capitalizes on expertise across fields, with Miner’s lab supplying insight into kidney biology, Suleiman contributing proficiency in advanced imaging methodologies and cell biology, and Genin offering expertise on mechanical forces in living systems. The team plans to employ state-of-the-art imaging techniques, including super-resolution microscopy, to visualize podocyte architecture in unparalleled detail. Additionally, they will use methods to gauge and manipulate mechanical forces exerted on cells.
The team indicated that their foundational scientific discoveries could set the stage for translational research aimed at creating new therapies for Alport syndrome and potentially other kidney ailments. With fresh insights into podocyte architecture and advanced mechanobiological models, they can develop novel strategies to aid podocytes in maintaining their connection, even when under duress.
“As a physician-scientist, I’m driven by the opportunity to transition from molecular-level discoveries to tangible clinical benefits for patients,” Suleiman expressed. “This kind of collaborative research is crucial for making those advancements.”
Originally published on the McKelvey School of Engineering website
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