Oct. 4, 2010

Three receive $1.5 million innovator awards

Three Cornell faculty members have received National Institutes of Health Director's New Innovator Awards, which includes $1.5 million over five years to stimulate innovative research and support promising new investigators who are studying biomedical or behavioral research conditions. They are: Maria Julia Felippe, associate professor of veterinary medicine; Ruth E. Ley, assistant professor of microbiology; and John C. March, assistant professor of biological and environmental engineering.

Felippe, of the College of Veterinary Medicine, will use the funds to challenge current thinking on common variable immunodeficiency (CVID), a disease that renders people and horses highly susceptible to recurrent bacterial infections.

CVID is the most frequent clinically relevant primary immunodeficiency in humans and is a mixed group of heterogeneous conditions linked by a lack of ability to produce antibodies that fight pathogens. CVID in humans has challenged the field of clinical immunology in regards to etiology and, consequently, therapeutic intervention. Although traditional thinking presumes CVID is a genetic disorder, data suggests that only a minor percentage of the affected patients are known to have genetic mutations, and the disease manifests later in life, leading Felippe to pursue a different line of thinking.

"We hypothesize that CVID in the horse is an epigenetic disease," Felippe said, meaning that it alters the activity, or the expression, of genes without changing their structure. "This could explain why the disease does not appear until later in life. It could also account for our inability to link a genetic mutation to the condition in more than 80 percent of the human patients."

Ley, of the College of Agriculture and Life Sciences (CALS) , will use the grant to study a metabolic syndrome model in mice and its correlation with certain gut microbe communities.

"A growing number of chronic diseases are linked with an imbalance in gut microbial communities," said Ley. "The aim of this research is to find a way to manipulate the composition of microbial communities to promote health. Microbes are generally beneficial, but there's a real possibility that having the wrong mix can be detrimental to health."

Metabolic syndrome is represented by such health factors as heightened blood pressure, elevated insulin and excess body fat. Ley's research will examine how the adaptive immune system responds to shape microbe communities within the body, and the role of such a response in either encouraging or discouraging the presence of metabolic syndrome. As a result, Ley hopes to develop a route of "vaccinating" against or treating microbe communities that lead to the development of metabolic syndrome in mice -- and eventually humans, as well.

"If we can do it in the context of this animal model of metabolic syndrome, perhaps we can do it in other disease contexts too," she said.

March, also of CALS, will use the award to examine how gut bacteria can be used to signal intestinal cells to function like insulin-producing beta cells in models of type I diabetes. With this research, March hopes to create an inexpensive and easy therapeutic method for people with this chronic disease.

"An exciting aspect of this research is the potential to treat a wide variety of diseases using the broad capabilities of bacteria engineered to communicate with their host," March said.

In type I diabetics, the beta cells in the pancreas fail to produce insulin, requiring routine insulin injections to control the blood sugar levels. In mouse models, March has successfully manipulated intestinal cells to function in a beta cell-like manner -- producing insulin in response to glucose -- with oral consumption of commensal bacteria. If this treatment method translates successfully to humans, it could mean a simple oral treatment that would mediate long-term effects of diabetes and eliminate the use of injections -- for just pennies a day.