My laboratory studies the genetics of cardiovascular disease using both the human and the mouse as a model system.
The Marchuk lab has spent the last 22 years identifying genes that cause Mendelian syndromes of vascular dysmorphogenesis through its human studies. Researchers have identified seven different genes that cause a variety of vascular malformations (capillary malformations, venous malformations, arteriovenous malformations, cavernous malformations). They have learned that in addition to the inherited mutation, somatic mutations in these same genes appear to be required to initiate the focal lesion development. The Marchuk lab is continuing these genetic and genomic studies with vascular malformation tissue.
The Marchuk lab's mouse studies are particularly interested in harnessing the power of mouse genetics to map novel genes that affect the severity and progression of disease in mouse models of disease. Researchers begin with an animal model of the disease, such as a surgically-induced or transgenic model of disease. The surgical intervention or the transgene acts as a sensitizer to create the disease in the animals. These sensitized models often exhibit drastically different rates of disease progression or outcome depending on the inbred strain employed.
Using genetic crosses with the sensitizer, scientists in this lab map and identify the genes underlying loci that influence disease outcome using both quantitative trait locus mapping and genome wide association across many strains. Using this approach, researchers have identified genes and gene variants that drastically alter the phenotype and outcomes of mouse models of cardiomyopathy, ischemic stroke, and critical limb ischemia. The orthologs of the modifier genes discovered in the mouse models are further studied for their role in the disease pathology as well as investigated in the corresponding human disease populations by DNA sequencing and SNP association studies.
Douglas Marchuk received his Ph.D. from the University of Chicago in 1985. Dr. Marchuk is a James B. Duke Professor and also serves as the Director of the Division of Human Genetics.