The Cardiovascular Research Center at Massachusetts General Hospital

Calum A. MacRae

Calum A. MacRae

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Lab Overview

How does rhythm resonate through the heart?

Our lab is interested in the fundamental cellular and molecular mechanisms of common or 'complex' cardiovascular diseases. In order to understand these disorders we study several complementary areas of biology, including:

1. Cell fate in the cardiovascular system - Not all cardiomyocytes or endothelial cells are created equal. Using cellular and developmental biology we are addressing how genetic and epigenetic factors regulate the differentiation and maintenance of cell fates within the cardiovascular system.

2. Genetic basis of common cardiovascular disease – Etiologic heterogeneity is one of the most difficult problems to overcome in genetic studies. We are using complementary approaches in humans and model organisms to understand how defects in cardiovascular structure and function may result from perturbations in many different pathways, and how we might be able to use novel phenotyping tools to discriminate between these distinct pathways. As etiologic heterogeneity is overcome, we will be able to define the each of the discrete causes of common cardiovascular disorders such as atrial fibrillation, coronary artery disease and heart failure. Ultimately, understanding all of the basic mechanisms underlying these common disorders will allow us to develop novel diagnostic tools and therapies tailored to the individual.

3. Integrative biology - Genotype alone is rarely predictive of phenotype in human disease. While human genetic studies identify critical insights into the complex underpinnings of disease, understanding how these genetic defects result in a range of human phenotypes will require quantitative analyses of the effects of gene-environment interactions on the physiology of the intact organ or organism. We are developing automated, high-throughput physiologic assays for the zebrafish to enable such quantitative approaches, as well as to allow large-scale genetic and chemical screens focusing for the first time on functional phenotypes.

Common disease does not often result from "all or nothing" defects, but rather is the consequence of the cumulative effects of subtle functional abnormalities and common stressors. Through understanding how normal cardiovascular structure and function are patterned and how those patterns are perturbed by genetic mutation and environmental factors, we hope to be able to break down the apparent 'complexity' of common human diseases.

Recent News

    • Congratulations to Patrick T. Ellinor and David Milan for being named principal
       investigators in the CVRC.

For patients interested in seeing Dr. MacRae in his clinical practice, click here to find out more or call 866-MGH-8910.

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Massachusetts General Hospital the cardiovascular research center