The Division of Gene Regulation and Drug Discovery conducts pioneering research that not only uncovers the genetic causes of major metabolic diseases such as type 2 diabetes, but also develops revolutionary therapies that precisely target the abnormal gene expression responsible for these diseases. By preventing the development of metabolic syndrome (obesity, high blood pressure, insulin resistance) through targeted therapies, we can reduce the incidence of other serious diseases such as heart disease, stroke and cancer.
Metabolic Syndrome and Obesity
Obesity has evolved into a worldwide epidemic affecting both industrialized and developing countries. Obesity is defined by the National Institutes of Health as having a BMI (body mass index) of 30 or above. More than one third of the U.S. population is obese, according to a 2007 study conducted by the Centers for Disease Control and Prevention. Obesity represents a serious public health concern as it is associated with metabolic syndrome (also known as syndrome X), a group of disorders leading to atherosclerotic heart disease, type 2 diabetes , stroke, cancers of the breast, digestive and reproductive tracts and possibly Alzheimer's disease.
Metabolic syndrome is defined by the following:
- Central obesity (fat concentrated around the waist)
- High blood pressure
- High triglycerides with low HDL cholesterol (dyslipidemia)
- High blood glucose (impaired glucose tolerance, a.k.a. insulin resistance)/Type 2 diabetes
Targeting Disease on the Molecular Level
The division, headed by Barry M. Forman, M.D., Ph.D., focuses on nuclear receptors (receptors in the cell’s nucleus), proteins that bind to genes, turning them on and off. These receptors respond to small molecules such as lipid metabolites, hormones and drugs, and then stimulate gene activity. By understanding the structure and function of these nuclear receptors, particularly a newly-discovered class called orphan receptors, Forman and colleagues can custom-tailor drugs to prevent activation of undesirable genes. Several new hormones have also been discovered to be involved in diabetes and atherosclerosis (which leads to heart disease and stroke). A major breakthrough is the recent discovery of a hormone called androstanol. Most hormones activate gene expression, but androstanol turns it off. Building on this knowledge, Forman is investigating other small molecules that may be able to inactivate gene expression, thereby stopping the development of metabolic disease.