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(301) 496-0844
Our laboratory focuses on the identification and understanding of genes involved
in human disease, using positional cloning techniques along with data and tools
provided by the Human Genome Project.
Our prior research led to the identification of the genes for cystic fibrosis,
neurofibromatosis and Huntington's disease. More recently, we identified the genes
for the M4 type of adult acute leukemia, Alagille syndrome and multiple endocrine
neoplasia type I (MEN1). We are now investigating the normal and abnormal function
of the MEN1 gene, using a mouse knockout model and other biochemical approaches.
In April 2003, we led a team that identified the gene responsible for Hutchinson-Gilford progeria syndrome (HGPS), which is the most dramatic form of premature aging.
We found that a point mutation in the lamin A (LMNA) gene produced an abnormal
lamin A protein that leads to instability of the nuclear membrane in cells of
progeria patients. We are now engaged in efforts to identify possible therapies
to prevent or reduce these nuclear membrane irregularities, and are also working
with collaborators to explore the possible role of the LMNA gene in the normal
aging process.
On a different front, a major project in our lab focuses on extending the positional
cloning approach to more difficult, non-Mendelian problems. We are pursuing the
genetic basis of Type II diabetes mellitus by studying a large cohort of affected
sib pairs and relatives collected in Finland. We are searching for genes conferring
susceptibility to diabetes, or to intermediate traits such as insulin resistance,
in more than 5,000 individuals. Using a genome scan followed by fine mapping,
we have identified regions of chromosomes 6, 11, 14, 20, 22 and X that apparently
harbor diabetes susceptibility genes. We are now applying high throughput genotyping
of single nucleotide polymorphisms (SNPs), using mass spectrometric technology,
to search for the precise variants responsible.