The Cardiovascular Research Center at Massachusetts General Hospital

John Mably, PhD

John Mably, PhD

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Lab Overview

The focus of my research is the characterization of zebrafish mutations that affect cardiac development. My research currently centers on the study of three zebrafish mutants collectively referred to as the "big hearts" (valentine, heart of glass, and santa). The hearts are huge, but thin-walled because the myocardium does not thicken as in the normal heart. The number of cells is not altered, implicating a defect in the concentric growth of the myocardium in these mutants. They have endocardium, but do not develop endocardial cushions, which give rise to valves.

The genes responsible for these mutations have been identified and we are currently looking at the relationship between these newly defined genes and the phenotype of the mutants. The similarity between the phenotypes of the three big hearts suggests the intriguing possibility of a common pathway. We can easily examine overexpress (by RNA injection) or knockdown (by antisense morpholino oligomers) these genes in the zebrafish and together with biochemical approaches we hope to define the interactions between them.

Two of these three genes have never been described previously, and none of the three have been examined in the context of cardiac development. In addition, the development of the zebrafish heart is very similar to that of the early mammalian embryo so that any insights provided by this work will be extendable to human studies with relevance for the study of human cardiac disease.

Collaborative Relationships
John Mably's lab is part of the Developmental Biology Program.

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