BBS Faculty Member - Jonathan Seidman

Jonathan Seidman

Department of Genetics

Harvard Medical School
New Research Building, Room 256
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-7871
Fax: 617-432-7832
Email: seidman@genetics.med.harvard.edu
Lab Members: 10 postdoctoral fellows, 1 graduate student



Work in the Seidman laboratory (Dept of Genetics, HMS) is directed toward identifying gene defects that cause inherited heart disease and defining the pathways by which these mutations mediate disease. We begin by using human genetic techniques to identify disease-causing mutations that alter cardiac structure and function. The advent of whole exome sequencing approaches and whole genome sequencing approaches has lead to the discovery of a host of disease-causing mutations. Most recently we have focused on identifying gene mutations that cause congenital heart disease, dilated cardiomyopathy and hypertrophic cardiomyopathy.

Identified mutations are modeled in mice or iPS cells. The biochemical consequences of these mutations are elucidated in these model systems. For example, we have recently constructed iPS cells that carry truncation mutations in the TTN that encodes the large sarcomere protein titin using the CAS9/CRISPR gene editing approach. These iPS cells were grown in 3-D cultures and the consequences of these mutations on contraction were measured. Similarly approaches are being used to assess the consequences of chromatin modifying gene mutations that cause congenital heart disease and mutations that cause hypertrophic cardiomyopathy. These analyses have led to the recognition that TTN mutations cause disease by reducing the amount of functional protein, while hypertrophic cardiomyopathy mutations frequently cause disease by creating a ‘poison polypeptide’. The mechanism(s) by which chromatin modifying gene mutations cause congenital heart disease remains largely unknown.



Last Update: 7/22/2015



Publications

For a complete listing of publications click here.

 


 

Jiang J, Wakimoto H, Seidman JG, and Seidman CE. Allele-specific silencing of mutant Myh6 transcripts in mice suppresses hypertrophic cardiomyopathy. Science. 2013;342(6154):111-4.

Zaidi S, Choi M, Wakimoto H, Ma L, Jiang J, Overton JD, Romano-Adesman A, Bjornson RD, Breitbart RE, Brown KK, et al. De novo mutations in histone-modifying genes in congenital heart disease.
Nature. 2013;498(7453):220-3.

Jiang J, Burgon PG, Wakimoto H, Onoue K, Gorham JM, O'Meara CC, Fomovsky G, McConnell BK, Lee RT, Seidman JG, et al. Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis.
Proc Natl Acad Sci U S A. 2015.

Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, et al. Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.
Sci Transl Med. 2015;7(270):270ra6.



© 2015 by the President and Fellows of Harvard College