Our goal is to understand how naturally occurring human genetic variation protects (or predisposes) some people to cardiovascular and metabolic disease—the leading cause of death in the world—and to use that information to develop therapies that can protect the entire population from disease. Our strategy is to identify patients, families, and cohorts with disease; to use genetic techniques such as genome-wide association studies and exome sequencing to identify novel DNA variants and genes linked to disease; to use human cell-based models and mouse models to understand how the DNA variants affect gene and protein function; and to use these mechanistic insights to begin the process of developing new therapies that will benefit patients and populations. In particular, we are interested in using human pluripotent stem cells to create human-derived tissues, containing specific DNA variants, as genetic disease models in which environmental and epigenetic influences have been minimized. We also aim to use stem cells to enable re-“gene”-erative medicine, in which a patient’s own cells can be genetically cured or made resistant to disease and then transplanted back into the body as a durable treatment.
 
Selected references:
 
1. Musunuru K, Pirruccello JP, Do R, et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med 2010;363:2220-7.
 
2. Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical, and population relevance of 95 loci for blood lipids. Nature 2010;466:707-13.
 
3. Musunuru K, Strong A, Frank-Kamenetsky M, et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 2010;466:714-19.
 
4. Musunuru K, Kathiresan S. Genetics of coronary artery disease. Annu Rev Genomics Hum Genet 2010;11:91-108.
 
5. Musunuru K, Domian IJ, Chien KR. Stem cell models of cardiac development and disease. Annu Rev Cell Dev Biol 2010;26:667-87.

Bio-Sketch

Dr. Kiran Musunuru is Assistant Professor of Stem Cell and Regenerative Biology at Harvard University and Associate Physician at Brigham and Women's Hospital. Dr. Musunuru received his M.D. degree from Weill Cornell Medical College, his Ph.D. degree from The Rockefeller University, and his M.P.H. degree from Johns Hopkins Bloomberg School of Public Health. He trained in Internal Medicine at Brigham and Women's Hospital and Cardiovascular Medicine at Johns Hopkins Hospital, followed by postdoctoral work at Massachusetts General Hospital and the Broad Institute of MIT and Harvard. Dr. Musunuru's research focuses on the genetics of cardiovascular and metabolic diseases.