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Our Genetic Studies


Kovler Diabetes Center is recognized worldwide for its leading-edge research into monogenic diabetes, a rare form of the disease.

In some cases, patients with monogenic diabetes have been able to switch from insulin injections to sulfonylurea pills. For more details, see our monogenic diabetes website.

Kovler developed a unique, long-term method for the study of patients with monogenic diabetes. Patients are invited to enter their names into a registry where details about their condition are recorded, as well as their medical histories and any patterns of diabetes in their families. Our monogenic diabetes registries have positioned Kovler Diabetes Center as a leading institution in the study of monogenic diabetes. Read more about the registries.

Kovler researchers are studying monogenic diabetes on multiple fronts, contributing toward the body of knowledge that may help science develop a cure. Our team of key researchers includes:

Graeme I. Bell, PhD

Nancy Cox, PhD

Louis H. Philipson, MD, PhD, FACP

Siri Atma W. Greeley, MD, PhD


Graeme I. Bell, PhD
Director, Diabetes Research and Training Center (DRTC)
Louis Block Professor of Medicine

Nancy J. Cox, PhD
Professor and Chief of the Section of Genetic Medicine
Department of Medicine, University of Chicago

Dr. Graeme Bell, a researcher in the University of Chicago’s Howard Hughes Medical Institute, was part of the team that first cloned the insulin gene. He has since cloned the gene for the insulin receptor. Bell also discovered and characterized a family of similar proteins that control transport of glucose out of the bloodstream and into cells.

In a landmark paper in 1991, the Bell lab mapped MODY1, the gene responsible for an unusual form of early-onset diabetes, to a small region on chromosome 20. This was the first time genetic techniques had been used to determine the chromosomal location of a gene that could cause diabetes. This knowledge allowed researchers to successfully predict which children from a given family would eventually develop diabetes.

In 1992, the Bell lab found MODY2. Bell and colleagues discovered that mutations of the gene for the enzyme glucokinase caused early-onset type 2 diabetes in a different family. In 1995, the Bell lab mapped MODY3 to a specific region on chromosome 12. In 1996, Bell and colleagues mapped NIDDM1, the gene responsible for a significant proportion of diabetes in Mexican-Americans, to one end of chromosome 2.

In 1997, the Bell lab found that patients from MODY3 families had one of several different mutations in the gene for hepatocyte nuclear factor 1a (HNF-1a), but healthy subjects had normal copies of the gene. Finding MODY3 led to the rapid discovery of MODY1, a functionally related gene known as HNF-4a.

In 2000, in a finding that provided an enormous boost for scientists interested in either diabetes or genetics, a team led by Bell and Dr. Nancy Cox identified the major susceptibility gene for type 2 or non-insulin-dependent diabetes mellitus (NIDDM) in Mexican-Americans. The gene pinpointed a new and unexpected biochemical pathway leading to diabetes, and it suggests novel approaches to prevention, diagnosis and treatment. This was the first time that a genome-wide approach has successfully led to the identification of a susceptibility gene responsible for a common, genetically complex disorder.

Research in the Bell and Cox laboratories is focused on identifying the genes and pathways that determine susceptibility to diabetes and its complications, then using this information to improve diagnosis and treatment. The Bell lab focuses on the molecular aspects of these studies, while the Cox lab focuses on statistical genetic analysis.

Bell and Cox also conduct studies of permanent neonatal diabetes with Louis H. Philipson, MD, PhD; Drs. Julie Stoy, Honggang Ye, Hiroya Sakuma and Soo-Young Park; and Ms. Veronica Paz. Their studies of type 2 diabetes, a polygenic form of diabetes, showed that genetic variation in the cysteine protease calpain-10 affected risk of this form of diabetes. Ongoing studies of the biology of calpain-10 carried out by Drs. Honggang Ye and Hiroya Sakuma suggest that it regulates, at least in part, insulin receptor levels on the plasma membrane.


Louis H. Philipson, MD, PhD, FACP
Professor of Medicine and Pediatrics
Director, University of Chicago Kovler Diabetes Center  

Louis Philipson, MD, PhD, is an endocrinologist specializing in diabetes. In his research, he studies the biophysical, molecular and genetic aspects of insulin secretion, and the enetics of diabetes.

Philipson’s research has focused on ion channel regulation of insulin secretion, use of biosensors to report cellular activity, and detection of reactive oxygen species in insulin secreting cells. His major translational research activity is in monogenic diabetes, both neonatal diabetes and genes associated with MODY, with his colleague, Dr. Graeme Bell.

Employing the tools of molecular biology, electrophysiology and live cell fluorescence confocal imaging, Philipson studies the role of ion channels in insulin secretion. He has published a series of studies on the role of repolarizing potassium channels in the beta cell, highlighted by a 2007 paper in Cell Metabolism on action potentials, calcium flux and insulin secretion in the Kv2.1 null mouse, a mouse model lacking a delayed rectifier potassium channel.

Philipson recently was a co-discoverer of insulin gene mutations causing neonatal diabetes, a novel class of mutations causing diabetes through beta cell ER stress. These mutations are now known to be the second most common cause of permanent neonatal diabetes as well as rare causes of later onset diabetes. Philipson is a resource for neonatal diabetes in the United States, with more than 20 patients diagnosed with KCNJ11 mutations and transferred to oral agents from insulin in the last two years. He has also recently established the first United States registry for neonatal diabetes with Bell.

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Siri Atma W. Greeley, MD, PhD
Assistant Professor of Pediatrics
University of Chicago Medical Center

Siri Greeley, MD, PhD, is a pediatric endocrinologist who sees children with all types of endocrine disorders or concerns, specializing in the treatment of infants, children and teens with all types of diabetes. Through basic and clinical research, Dr. Greeley hopes to shed light on the full spectrum of childhood diabetes. His research focuses on how best to classify the diabetes type of each individual patient. Dr. Greeley is particularly interested in monogenic diabetes, which is often unrecognized, even though this group of disorders may represent as much as 2 to 3 percent of all diabetes cases.

Dr. Greeley recently designed and implemented the first national Web-based registry of patients with neonatal diabetes, who are more likely to have an underlying monogenic cause. He is helping to establish the University of Chicago as a national center for the study of monogenic diabetes. By uncovering the mechanisms of beta cell failure in patients with relatively simple genetics, Dr. Greeley and his colleagues hope to uncover the causes and mechanisms of all forms of diabetes.

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