Congratulations to Wei Shi, a postdoctoral fellow in the Conlon Lab, and Frank L. Conlon, Ph.D., Professor of Biology and Genetics, in collaboration with the Lab of Christine Edry Seidman, M.D., Director, Cardiovascular Genetics Center; Professor, Harvard Medical School; Cardiovascular Medicine, and Jonathan G. Seidman, Ph.D., Henrietta B. and Frederick H. Bugher Foundation Professor of Genetics, for publishing article, titled “Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1”, in the journal Circulation Research.
In these studies, a recent exome sequencing of a cohort of congenital heart disease probands identified a single point mutation in CHD (chromodomain helicase DNA binding protein)-4 — a component of the NuRD (nucleosome remodeling and deacetylase) complex. The authors generated a mouse model of the human patient mutation and showed that the mouse suffers from noncompaction cardiomyopathy (NCM). Through detailed molecular analyses, the authors unmoved the pathways downstream of the mutant CHD4 and, using a pharmacological approach, introduced the metalloproteinase ADAMTS1 and rectified the cardiac compaction defect. The work was featured in the June 23, 2023, Vol 133, Issue 1 of the journal Circulation Research and can be read online now.