HomeResearchIntramural ResearchResearch Branches at NHGRIGenome Technology Branch Collins Lab

Francis S. Collins, M.D., Ph.D. Director National Human Genome Research Institute Senior Investigator Genome Technology Branch Head Molecular Genetics Section B.S. University of Virginia, 1970 Ph.D. Yale University, 1974 M.D. University of North Carolina, Chapel Hill, 1977 (301) 496-0844 (301) 402-2218 fc23a@nih.gov Building 31, Room 4B09 31 Center Dr, MSC 2152 Bethesda, MD 20892-2152 Selected Publications

Dr. Collins' laboratory seeks to identify and understand genes involved in a range of human diseases. His group also is developing animal models of genetic disorders to test potential therapeutic approaches.

A significant project in Dr. Collins' laboratory is progeria, a rare genetic disorder characterized by rapid, premature aging. Collaborating with investigators at the Progeria Research Foundation and other research institutions, his group identified the genetic mutation responsible for Hutchinson-Gilford progeria syndrome (HGPS), the most dramatic form of progeria. HGPS patients typically die from cardiovascular complications in their teens. The Collins laboratory recently discovered that a point mutation in the lamin A (LMNA) gene abnormally shortens the normal version of the encoded protein-progerin-by 50 amino acids near the C-terminus. They also found that HGPS is associated with significant changes in the shape of the nucleus; these structural defects worsen as HGPS cells age in culture. The severity of nuclear changes correlates with an increase in mutant progerin, and introducing mutant progerin into normal cells induces the same nuclear changes.

Because most progeria patients are in extremely fragile health, there are few opportunities to conduct human trials of potential therapies. Dr. Collins' group is developing an animal model of progeria by reengineering the human LMNA gene to carry the HGPS mutation and inserting it into the germline of a mouse. If successful, this mouse model will offer a resource for screening potential progeria therapies, such as statin drugs (to prevent cardiovascular disease) and farnesyl transferase inhibitors (since lamin A is farnesylated). His group also is exploring the possible role of the wild-type LMNA gene in the aging process. They are collecting and analyzing DNA from a cohort of about 600 centenarians to determine whether there is something unique about their LMNAgene sequence that promotes longevity.

In addition, Dr. Collins' laboratory investigates multiple endocrine neoplasia type 1 (MEN1), a hereditary cancer syndrome. In 1997, his laboratory, collaborating with other NIH researchers, identified the MEN1 gene and found that mutations in this tumor suppressor gene cause multiple benign tumors of the parathyroid and pituitary glands, as well as pancreatic islet cell tumors. His laboratory is using chromatin immunoprecipitation microarrays (ChIPchip technology) to study how menin, the gene product, affects gene regulation. They also have developed and extensively studied a conditional knockout mouse model to determine how loss of the normal protein encoded by this gene affects a variety of tissues.

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Last Reviewed: June 14, 2007