VIP Group Forms Basis For NIH Grant To Study Kidney Disease

Over the past several years, David Rubenstein, an associate professor in the Department of Biomedical Engineering at Stony Brook University, has added a new organ to his research - the kidney.

Rubenstein, who usually focuses his research on the vascular system and the heart and how cardiovascular disease is initiated or progresses, is now helping clinicians in nephrology from Stony Brook Medicine understand how kidney disease starts and progresses through the lens of physical forces.

The research originated with a group of undergraduate students through the university's Vertically Integrated Projects (VIP) Program, which unites students and faculty in multidisciplinary teams that work on long-term projects in research, design, innovation and entrepreneurship.

The students, averaging 15 to 20 every year, helped to lay the groundwork for this work. They helped bridge the gap between two faculty members' discussion and a grant-funded study, the "Role of PLVAP in Glomerular Endothelial Cell Injury," from the NIH's National Institute of Diabetes and Digestive Kidney Disease, in the amount of $3,034,933.

The group was very interested in how endothelial cells in the kidney function under various physiological and pathological conditions. About a year ago, the PI of the grant, Chelsea Estrada, a nephrologist at Stony Brook Medicine, found that a structural protein - Plasmalemmal Vesicle-Associated Protein (PLVAP) - is expressed in specific kidney endothelial cells only during injury. They theorized that this protein could alter the transmission of mechanical forces.

That's when Rubenstein became more involved. "I would bring in the engineering aspects," he said. "Do the mechanical forces affect how that protein behaves? That's a specialty of my lab."

The group set up a couple of experiments, found some interesting results, and wrote and submitted the grant.

Since this is not a long-standing field, there is not much history. "So there's a lot of figuring out what the right conditions are and doing it in a way that represents the physiology appropriate so that the results are meaningful," said Rubenstein, now a collaborating investigator on the grant. " The VIP team helped us comb the prior literature to ensure that we apply appropriate experimental conditions."

Many people with kidney disease are on waiting lists for transplants, and they tend to stay on dialysis. It could be 10 to 15 years before a kidney becomes available. "Unlimited funds to solve kidney disease would be the best thing," said Rubenstein. "This work would potentially address how physicians deal with kidney disease and perhaps come up with new ideas, or new targets, instead of relying heavily on dialysis. Perhaps a new therapeutic and new intervention strategies can be developed to reduce the current dependency on both kidney donors and dialysis as a very long-term goal."

"A multidisciplinary approach is needed to investigate these specialized kidney cells, which have historically been difficult to study. Uncovering new mechanisms of their injury has the potential to lead to new therapeutics for prevention and treatment of chronic kidney disease," said Estrada.

Rubenstein, who holds his BE, MS and PhD degrees in biomedical engineering from Stony Brook, described the Vertically Integrated Projects program's potential: "The promise and the hope of the VIP program is to bring together lots of interdisciplinary knowledge and initiate new projects and ideas that can really come to fruition."

Robert Kukta, senior associate dean for education and innovation and faculty advisor for the VIP program said, "I'm very grateful for exceptional faculty who engage students from across the university in their research. It creates a rich collaborative environment that many students will not experience until after they graduate."

- Debra Scala Giokas