Molecular Genetics Section (MGS) researchers study a range of inherited conditions, from common to rare. Among the rarest is the Hutchinson-Gilford Progeria syndrome (HGPS), the most dramatic form of premature aging in humans. HGPS patients typically die from heart disease in their teens. Dr. Collins' laboratory discovered that a mutation in the lamin A gene (LMNA) causes HGPS, producing a toxic protein that interferes with the structure and function of the cell nucleus. Prior information about the biology of lamin A suggested that the amount of the toxic protein might be reduced by use of farnesyltransferase inhibitors (FTIs), and experiments in the lab have shown that these drugs improve the nuclear abnormalities of HGPS. Using a mouse model developed in the lab, it has been possible to demonstrate that FTIs can reverse the cardiovascular disease. This research has supported the development of a clinical trial of FTIs in humans, which has now been shown to reduce stiffening of major arteries, and even to prolong survival.
The group studies common diseases, including type 2 diabetes (T2D), performed collaboratively with Finnish scientists, initially using a genome-wide association study (GWAS). This collaboration has expanded into several worldwide consortia studying T2D, which have identified over 80 susceptibility genes for T2D and hundreds of genetic variants affecting glucose, body weight and lipids. Many of these variants are associated with abnormal insulin secretion or processing, and most are in DNA that is not part of genes, but which may regulate genes. To study these variants, the lab uses a functional genetic technology called ChIP-seq. This work has uncovered a new category of regulatory signals, called stretch enhancers, that play a crucial role in determining whether genes are on or off in a particular tissue. The Collins laboratory is using next generation sequencing techniques to search for rare variants of larger effect in T2D.
Francis S. Collins, M.D., Ph.D., is Director of the National Institutes of Health (NIH). In that role he oversees the work of the largest supporter of biomedical research in the world, spanning the spectrum from basic to clinical research.
Dr. Collins is a physician-geneticist noted for his landmark discoveries of disease genes and his leadership of the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book. He served as director of the National Human Genome Research Institute at the NIH from 1993-2008.
Dr. Collins' research laboratory has discovered a number of important genes, including those responsible for cystic fibrosis, neurofibromatosis, Huntington's disease, a familial endocrine cancer syndrome, and most recently, genes for type 2 diabetes, and the gene that causes Hutchinson-Gilford progeria syndrome, a rare condition that causes premature aging.
Dr. Collins received a B.S. in chemistry from the University of Virginia, a Ph.D. in physical chemistry from Yale University, and an M.D. with honors from the University of North Carolina at Chapel Hill. Prior to coming to the NIH in 1993, he spent nine years on the faculty of the University of Michigan, where he was a Howard Hughes Medical Institute investigator. He is an elected member of the Institute of Medicine and the National Academy of Sciences. Dr. Collins was awarded the Presidential Medal of Freedom in November 2007 and the National Medal of Science in 2009.
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Last Updated: January 5, 2015