BBS Faculty Member - Calum MacRae

Calum MacRae

Department of Medicine
Cardiovascular Research Center

Brigham and Women's Hospital
Thorn 11
75 Francis St.
Boston, MA 02115
Tel: 857-307-0301
Fax: 857-307-0300
Email: camacrae@bics.bwh.harvard.edu
Lab Members: 7 postdoctoral fellows, 1 instructor
Visit my lab page here.



Our lab is interested in the biologic basis of cardiac and vascular disease. 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;

Unraveling the basis of regional cellular specification in the heart and vascular system - The basic cellular plan of the heart and vascular networks undergoes tremendous regional specialization during development. For example, gradients of myocyte function exist between the endocardium and epicardium, while each organ has a distinctive arterial or venous endothelium. Using the zebrafish and chick, we are combining classic developmental cell and molecular biology with high resolution in vivo cellular physiology to understand how genetic and epigenetic factors interact to generate and maintain this cellular diversity. Current projects include the generation of a functional fate map of the early heart, and dissecting the role of physiologic stimuli such as blood flow, mechanical or electrical signals in the patterning of the heart and vasculature.

Disease modeling in the zebrafish – The zebrafish is uniquely positioned as a vertebrate model amenable to high-throughput screening. We have developed robust, automated in vivo assays that enable us to phenotype cellular or integrated cardiovascular function in 96 or 384 well plates. These tools facilitate quantitative, scalable approaches to disease pathway dissection in genetic models of human cardiac and vascular disorders. Genetic screens are underway in these disease models to identify novel pathway members and to explore gene-environment interactions, in particular pharmacogenetics. Parallel screens of small molecule libraries are designed to identify probes for chemical biology strategies in these same diseases with the ultimate aim of identifying new therapeutics.

Genetics of human heart failure – We are also attempting to understand the genetics of common human cardiac and vascular disease. These syndromes have long been viewed as genetically “complex”, but we have based our work on the premise that much of the apparent complexity reflects limited phenotypic resolution. In our human studies we are reevaluating disease phenotypes in classic kin-cohorts to resolve the genetic architecture of heart failure and atherosclerosis. These cohorts also enable investigation of early pathophysiologic mechanisms in ‘preclinical’ individuals and offer an avenue for the rapid translation of new diagnostic or therapeutic approaches.



Last Update: 6/20/2014



Publications

For a complete listing of publications click here.

 


 

A Asimaki, S Kapoor, E Plovie, AK Arndt, E Adams, ZZ Liu, CA James, DP Judge, H Calkins, Ja Churko, JC Wu, CA MacRae,† AG Kléber,† JE Saffitz†. An In-Vivo Drug Screen in Zebrafish Identifies a Novel Modulator of Intercalated Disc Remodeling in Arrhythmogenic Cardiomyopathy. Science Translational Medicine 2014 (in press).

G Musso, M Tasan, C Mosimann, JE Beaver, E Plovie, LA Carr, HN Chua, J Dunham, K Zuberi, H Rodriguez, Q Morris, LI Zon, FP Roth,
CA MacRae. Novel cardiovascular gene functions revealed via systematic phenotype prediction in zebrafish. Development 2014 141:224-235.

JR Becker, S Chatterjee, TY Robinson, JS Bennett, D Panáková, CL Galindo, L Zhong, JT Shin, SM Coy, AE Kelly, DM Roden, CC Lim, and
CA MacRae. Differential activation of the natriuretic peptide receptors modulates cardiomyocyte proliferation during development. Development 2014 14:335-345.

D Panakova, A Werdich,
CA MacRae. Wnt11 patterns a myocardial electrical gradient via regulation of the L-type Ca2+ channel. Nature 2010 466:874-878.



© 2014 by the President and Fellows of Harvard College