Kevin Niswender, M.D., Ph.D.
Niswender named a Culpeper Medical Scholar
Kevin D. Niswender, M.D., Ph.D., is one of three young physician-scientists in the country to be named a 2006 Charles E. Culpeper Medical Scholar.
The scholarship program was established in 1988 to “nurture the career development of exceptionally promising physician scientists as they transition to becoming independent researchers at the best academic medical centers,” according to Partnership for Cures, the public charity that currently administers the program.
Niswender was selected from a pool of 34 applicants nominated by academic medical centers across the country.
“Kevin is an exemplary model of a physician-scientist, and he embodies the spirit of the Culpeper Scholarship,” said Jeffrey R. Balser, M.D., Ph.D., associate vice chancellor for Research.
The Culpeper Medical Scholarship provides a three-year award of $324,000. In addition to promoting physician scientist career development, the awards seek to accelerate the discovery of new treatments for life-threatening diseases, according to Partnership for Cures.
“We were all delighted to hear the news of Kevin's Culpeper Award,” said Eric G. Neilson, M.D., chairman of Medicine. “Dr. Niswender is working on the cutting edge and has pushed the Department into new and vital areas of research in diabetes and obesity. His award is great acknowledgement of our progress in supporting this area of discovery.”
“I'm very honored, and I'm excited about the project we proposed,” Niswender said. “It's a project that is 'outside the box,' and I believe it has a lot of potential, but would not likely be funded by agencies unwilling to take some risk.”
Niswender aims to identify lead compounds to advance the discovery of therapeutic drugs for obesity.
“One of the problems with obesity drug discovery is that much of the control of body weight regulation lives in the brain,” Niswender said. “And because the brain is such a heterogeneous organ, filled with different cell types, coming up with validated drug targets is very difficult for central nervous system diseases.”
Another problem is the lack of appropriate cell lines or culture systems for studying obesity, he said.
Body weight regulation “is an organismal process, but high-throughput screening for drug discovery happens in vitro.”
To marry the two, Niswender has proposed using a cellular surrogate — cultured pancreatic islets — to represent the hypothalamic neurons that regulate appetite and energy expenditure. In collaboration with Vanderbilt's High-Throughput Screening facility, part of the Vanderbilt Institute of Chemical Biology, Niswender will screen a “library” of small chemical compounds for those that act to potentiate insulin action in islets that have been cultured under conditions that replicate “obesity.”
“We're taking advantage of the functional similarities between hypothalamic neurons — their intracellular signaling, their electrophysiology, their stimulus-secretion coupling — and pancreatic beta cells,” Niswender said.
Niswender and his colleagues discovered how leptin and insulin signal in hypothalamic neurons to suppress appetite and increase energy expenditure.
“We believe that obesity is really a central nervous system disease,” Niswender said, “and we've identified what we think is a major pathophysiological process in the brain that leads to obesity. It really boils down to lesions that resemble insulin resistance in the brain.”
The high-throughput screen is designed to identify insulin sensitizers in pancreatic islets — compounds that should also act as insulin, and leptin, sensitizers in the brain and will hopefully function to combat obesity. These compounds might also point to new diabetes therapies.
“Obesity and metabolic syndrome is the defining disease entity of our era,” Niswender said. “And the rise of obesity and metabolic syndrome in children and young adults is really frightening.”
Niswender completed his M.D. and Ph.D. degrees at Vanderbilt University. He served his Internal Medicine residency at the University of Washington in Seattle and continued his training there with a fellowship in Metabolism, Endocrinology and Nutrition. He joined the Vanderbilt faculty in 2004.