Calum MacRae, M.D., Ph.D.

Brigham and Women's Hospital
Harvard Medical School

The MacRae lab is focused on understanding the genetic contribution to common cardiovascular disease using human studies and complementary high-throughput biology in the zebrafish.

Our lab is interested in the role of functional inputs such as mechanical forces, metabolism or electrical activity in refining the basic programs of cell specification and differentiation in cardiovascular development, disease, repair and regeneration.

In a multidisciplinary approach to these problems, involving group members who are geneticists, developmental biologists, physiologists, computational biologists and engineers, we are working in three main areas:

Cellular communication - Proper embryogenesis and organ function is critically dependent on finely-tuned intra- and intercellular communications. Our lab is devoted to further unravel the mechanisms via which populations of cells within the cardiovascular system propagate signals, interact with each other and coordinate their activities. To test our current hypotheses, we have developed several state-of-the-art imaging techniques to visualize a range of signals at cellular or sub-cellular resolution in the developing zebrafish.

Zebrafish as tools for drug discovery – Our lab is highly interested in developing systematic understanding of the relationship between genes and environment using high throughput, phenotype-driven genetic and chemical screens in the zebrafish. Our interest ranges from the most primitive cellular behaviors to more complex pathophysiological processes. Taking advantage of the scalability and rapid development of the zebrafish, we have used these startegies to study gene-gene and gene-environment interactions in development and in disease biology. Recently we used this approach to identify chemical suppressors of different genetic causes of heart failure, and we are now using the initial ‘hit’ compounds to explore new therapies for these conditions.

Human genetics - Many human diseases have arisen as clusters of unrelated disorders that share only some gross cardiac phenotype. We have begun to stratify these disorders and understand the mechanism using non-cardiac phenotypes through approaches as diverse as facial recognition, wearables and short term drug responses. We have an active human genetics effort based in the Cardiovascular Clinical Genetics Center, the Brigham Genomic Medicine group and the national Undiagnosed Diseases Network. In addition to traditional genomic approaches to gene discovery in disease families, we have developed a Next Generation Phenotyping platform in our ambulatory clinics that is designed to test and validate new technologies bringing cell biology or physiology to the bedside.

Biosketch

Calum MacRae is Vice Chair for Scientific Innovation at the Department of Medicine at Brigham and Women’s Hospital and Associate Professor of Medicine at Harvard Medical School. He is the leader of One Brave Idea, a group of leading scientists from multiple disciplines working together to understand the earliest stages of coronary heart disease (CHD). His clinical interests include the management of inherited heart disease and cardiac involvement in systemic diseases.

MacRae is a cardiologist, geneticist and developmental biologist who received his M.D. and Ph.D. from Edinburgh and London before coming to Boston in 1991. He completed postdoctoral fellowships in human genetics with Drs. Christine and Jon Seidman and in developmental biology with Dr. Mark Fishman, and received additional clinical training in internal medicine and cardiology before joining the Division of Cardiology at Massachusetts General Hospital in 2001. MacRae is a leading investigator at the Brigham and Women’s Hospital Genomics Center, a principal faculty member at the Cardiovascular Research Center and the Harvard Stem Cell Institute, and an associated member at the Broad Institute.