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
10 postdoctoral fellows, 1 graduate student

Work in the Seidman laboratory 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 map and identify disease-causing mutations that alter cardiac structure and function. Identified mutations are modeled in animals and then the biochemical consequences of these mutations are elucidated.

Most recently we have developed a new method, PMAGE or polony multiplex analysis of gene expression, for defining the complete RNA profile of a cell or tissue. Other methods of RNA profiling such as microarrays and SAGE (serial analysis of gene expression) do not assess RNAs expressed at low levels such those that encode transcription factors and signaling molecules. Using PMAGE we can detect RNAs that are present in as few as 0.3 RNA molecules per cell.

We are in the process of using PMAGE to study the consequences of gene mutations that cause cardiomyopathies (e.g. dilated cardiomyopathy and hypertrophic cardiomyopathy) as well as congenital heart diseases including tetralogy of Fallot, Holt-Oram Syndrome, atrial septal defect and conduction system disease.

References:

• Kim, J.B., et al., Polony Multiplex Analysis of Gene Expression (PMAGE) in a Mouse Model of Hypertrophic Cardiomyopathy. Science, 2007, in press June 8.
• Moskowitz, I.P.G., et al., A Genetic Pathway Including Id2, Tbx5, and Nkx2-5 Required for Cardiac Conduction System Development. Cell, 2007, in press.
• Hinson, J.T., et al., Missense mutations in the BCS1L gene as a cause of the Bjornstad syndrome. N Engl J Med, 2007. 356(8): p. 809-19.