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Douglas Marchuk

Professor
Molecular Genetics and Microbiology
919 684-1945
Research Interest: 
Genetics
Nucleic acid metabolism
Research Summary: 
The genetics of cardiovascular disease using both the human and the mouse as a model system.
Research Description: 

Over the course of the past 18 years at Duke, we have identified the causative genes for a number of different Mendelian disorders of vascular malformations. In addition to continuing our molecular analysis of mutations in these patients, we have generated animal models to further understand the disease pathogenesis and to generate and test new therapies.

In other projects we have harnessed the power of mouse genetics to map novel genes that affect the severity and progression of disease in mouse models of more common cardiovascular disease (eg. stroke and heart disease). We 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, we can map the loci that influence disease outcome. We call these risk factors “modifier loci” since they modify disease progression or outcome. The orthologs of the modifier genes discovered in the mouse models are then investigated in the corresponding human disease populations.

Publications: 
Fasudil decreases lesion burden in a murine model of cerebral cavernous malformation disease.
McDonald DA, Shi C, Shenkar R, Stockton RA, Liu F, Ginsberg MH, Marchuk DA, Awad IA.
Stroke. 2012. 43:571-4.

A locus mapping to mouse chromosome 7 determines infarct volume in a mouse model of ischemic stroke.
Keum S, Marchuk DA.
Circ Cardiovasc Genet. 2009. 2:591-8.

Tnni3k modifies disease progression in murine models of cardiomyopathy.
Wheeler FC, Tang H, Marks OA, Hadnott TN, Chu PL, Mao L, Rockman HA, Marchuk DA.
PLoS Genet. 2009. 5:e1000647.

Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis.
Akers AL, Johnson E, Steinberg GK, Zabramski JM, Marchuk DA.
Hum Mol Genet. 2009. 18:919-30.

A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations.
Gallione CJ, Solatycki A, Awad IA, Weber JL, Marchuk DA.
Genet Med. 2011. 13:662-6.