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Medical College of Wisconsin and Children’s Hospital of Wisconsin to Study the Genetics of Type 1 Diabetes

The Medical College of Wisconsin (MCW) and Children’s Hospital of Wisconsin Research Institute received a four-year, $4.3 million grant from the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases to investigate the genes involved in type 1diabetes (T1D).

Aron M. Geurts, Ph.D., associate professor of physiology, and Yi-Guang Chen, Ph.D., assistant professor of pediatrics and researcher at the Research Institute, are the principal investigators for the grant.

Dr. Geurts is with MCW’s Cardiovascular Research Center, Human and Molecular Genetics Center and Department of Physiology, and Dr. Chen is with MCW’s Department of Pediatrics and the Max McGee National Research Center for Juvenile Diabetes at Children’s Hospital of Wisconsin.

Type 1 diabetes accounts for approximately five percent of all diabetes cases in the United States, affecting about 1.3 million Americans.

The incidence of T1D has risen in recent years, and has led to a greater burden on families and healthcare providers. Patients diagnosed with T1D produce little or no insulin, a hormone that is essential for the utilization of food energy and the maintenance of glucose homeostasis. When metabolism does not function properly due to insulin deprivation or insulin resistance, diabetes can contribute to severe dehydration, tissue damage and an increased chance of heart attack and stroke.

This project will investigate genes on a number of chromosome regions that recent large-scale genetic studies have identified as possibly contributing to the development and progression of T1D.

Medical College of Wisconsin researchers were the first to demonstrate the innovative zinc-finger nuclease technology and among the first to apply transcription activatorlike effector nuclease (TALEN) technology for influencing genes.

These technologies will be used in this study to manipulate genes in an animal model of T1D in order to discover which genes are important to the development of the disease.

The results of this study will advance understanding about T1D and contribute to the development of new approaches for treating the disease.

Traditional genetic engineering strategies for manipulating the many genes under scrutiny in this study would take a tremendous amount of time and money. Medical College of Wisconsin researchers have developed innovative and rapid ways of making genetically modified models that are time and cost efficient.

This study is made possible by these advances in technology and creative researchers who incorporate state-of-the-art techniques into effective research designs. Dr. Geurts was selected for a prestigious National Institutes of Health Director’s New Innovator’s Award in 2011 for displaying these qualities in his research using zinc-finger nuclease technology to develop improved animal models of disease.

Medical College of Wisconsin faculty members joining the project as co-investigators are John Corbett, Ph.D., chairman and professor of biochemistry; Howard Jacob, Ph.D., Warren P. Knowles Professor in Human and Molecular Genetics, director of the Human and Molecular Genetics Center and professor of physiology; and Martin Hessner, Ph.D., professor of pediatrics and director of the Max McGee National Research Center for Juvenile Diabetes.

This award demonstrates a commitment to collaboration among a number of research centers and departments at both MCW and Children’s Hospital of Wisconsin.