Eric Delpire, Ph.D., professor of Anesthesiology, Molecular Physiology and Biophysics and director of the Anesthesiology Basic Science Research Division, has spent the past 15 years developing genetically altered mice for use in scientific research, and he now knows the value of his research in a very personal way.
Research using mouse models helped save his life.
Working in partnership with one of Vanderbilt University’s renowned resources for animal models, the Vanderbilt Transgenic Mouse/Embryonic Stem Cell Shared Resource, Delpire’s genetically modified knockout and knock-in mice have served as the basis for many high-impact journal articles, and labs from institutions across the United States depend on his mouse lineages to advance their own scientific investigations.
In 2011 Delpire began noticing an unusual skin growth which continued to increase in size. He was diagnosed with not one, but two cancers. The irony of the course of his ensuing cancer treatment was not lost on him.
“One of the chemotherapy components I took was an antibody developed from mouse research,” said Delpire. “I had a cancer mass, a lymphoma unusually located in the skin, and the antibody melted it in just three days.”
“B cell lymphomas express CD20, which is a cell surface marker,” Delpire explained. “The monoclonal antibody, called retuxan or retuximab, targeted those specific cancer cells and went right to it.”
Delpire did not slow down as he went through treatment. He is now in remission, having undergone additional radiation and chemotherapy. A husband and the father of three, he finds it hard to express enough gratitude for the research that has given him more years.
“I am curious, and I love what I am doing,” he said. “Having the cancer and seeing the incredible results confirms the value of animal research in general, and mouse research in particular. The fruit of this research was available at the right time for me.”
Delpire recently received NIH funding for his third study, a four-year, $2.53 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to study Kinase modulation of Na+-dependent Cl- coupled transporters in the mouse kidney.
He is also the principal investigator for two other studies funded by the National Institutes of Health (NIH) involving genetically altered mice. Since 2002, he has been the principal investigator in a multi-institution research consortium funded by the National Institute on Alcohol Abuse and Alcoholism to identify the molecular basis of alcoholism to develop better ways to treat and prevent the disease.
Delpire created conditional knockout mice targeting specific receptors in the brain that are likely involved in brain circuitries that modulate alcohol overconsumption and addiction. His mice are used by investigators in the consortium as they conduct electrophysiology, analysis of neurosteroids, behavior analysis and microarrays.
In the other study, Delpire is focusing on specific kinases — proteins which modify other proteins by either activating or inactivating them.
Since discovering two kinases 12 years ago that regulate chloride-dependent sodium and potassium co-transporters, or proteins that move sodium, potassium and chloride ions across the cell membrane, he has developed kinase-specific knockout and knock-in mice to pinpoint the physiological functions of these proteins.
By better understanding these functions, targeted therapeutic interventions may be developed to treat and prevent diseases such as epilepsy, nerve degeneration and high blood pressure.
“We are fortunate to have a world-class shared resource to help us derive genetically altered mice, such as those used by Dr. Delpire,” said Mark Magnuson, M.D., professor of Molecular Physiology and Biophysics and senior scientific co-director of the Vanderbilt Transgenic Mouse/Embryonic Stem Cell Shared Resource.
“The use of conditional mouse models is a foundational part of many investigators’ research here at Vanderbilt, and Dr. Delpire has used the resource in a remarkably impactful way. Indeed, by doing so he has become an international expert in his field, which is a win-win for everyone.”