The MCRI Center for Translational Genomics investigates genetic and biological mechanisms of heart and cardiovascular disease using a two pronged approach. The first approach seeks to identify genes identified that contribute to human cardiovascular disease through large scale genomic screens. The second approach uses molecular and cellular biology techniques complemented by the use of animal models to study genetic regulators of muscle development and their role in muscle disease. The convergence of the two approaches offers an exciting platform for discovering important biological mechanisms and genetic human variations that contribute to disease.
IDENTIFYING GENES ASSOCIATED WITH HUMAN DISEASE: Dr. Huggins believes firmly in the benefit of making primary discoveries of human disease whenever possible in humans. Within the past one to two decades the human genome sequence has been completed and a map of genetic markers suitable for studying disease associations has been established. Both candidate gene and genome-wide association studies are performed in the Huggins laboratory. A particular focus is the identification of genetic contributors to bicuspid aortic valve, hypertrophic Cardiomyopathy, dilated Cardiomyopathy as well as metabolic factors including lipoproteins and inflammatory markers. Recently, we are exploring the use of next-generation sequencing-based exome and transcriptome analysis for the comprehensive identification of rare and common coding variants associated with heart muscle disease. These large-scale genetic screens are supported by active collection of DNA and serum samples from patients of the Tufts Medical Center Cardiovascular Center.
ANALYSIS OF HYPERTROPHIC CARDIOMYOPATHY: Causative factors of heart muscle disease include environmental insults such as ischemia/infarction, high blood pressure, toxins, drug exposure and atypical genetic changes. Hypertrophic cardiomyopathy (HCM) is an example of a heart muscle disease caused by gene mutations. An active project in the Huggins laboratory is the analysis of how the formin family of genes contributes to heart muscle disease including HCM. As we explore the effects of formin gene variants on HCM we hypothesize that actin filament production and remodeling contribute to diverse types of muscle diseases.
CALCIFIC AORTIC VALVE DISEASE: Finally, Dr. Huggins has identified through genotype association study approaches genes that contribute to bicuspid aortic valve disease and calcific aortic valve disease. Current work is determining the role of pathway genes that contribute to bone formation in calcific aortic valve disease.
Research Administrator: Dionne Bradford