The MCRI Center for Translational Genomics, directed by Gordon Huggins, MD, 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.
Gordon Huggins, MD
Principal Investigator, Center for Translational Genomics and Associate Professor, Tufts University School of Medicine
Dr. Higgins graduated from Boston University and Pritzker School of Medicine, University of Chicago. He completed his Internal Medicine residency and Clinical Cardiology Fellowship at the Massachusetts General Hospital, Harvard University. Prior to coming to the MCRI, he spent 4 years at The Massachusetts General Hospital in the Cardiology Division. Drs Edgar Haber, Mu-En Lee and Jeffrey Leiden trained Dr. Huggins in molecular biology at the Cardiovascular Biology Laboratory in the Harvard School of Public Health. Currently, he is the Director of the Laboratory of Cardiovascular Genetics of the MCRI and is an Associate Professor of Medicine at Tufts University School of Medicine.
Marina Freytsis is investigating the genetic pathways that underlie Calcified Aortic Valve Disease (CAVD). She is currently looking at the Rb/CDK6 pathway, as it is important for regulating bone formation and several of its components that have been identified in genome-wide association studies of CAVD patients. By using in vitro cell culture and genetically modified mice, she hopes to elucidate the mechanisms leading to CAVD.
Dionne Bradford joined the MCRI in June 2006 as a Research Administrator. In this role she is responsible for identifying new funding opportunities, submission of grant proposals, and all post-award including financial tracking. Additionally, Dionne works closely with the Director of Administration and Finance on matters relating to research facilities, human resources, technology transfer, and compliance issues. Prior to joining the MCRI, Dionne worked for the CBR Institute/Harvard Medical School. Dionne is an alumna of the University of Massachusetts.