Description of CVI Expertise

CVI Program Unit(s):
Cardiovascular Development / Congenital Heart Disease

CVI Research Description:
Regulation of cardiac morphogenesis and function

Key Words: Cardiac development, morphogenesis, compaction, epigenetics, microgenomics, congenital heart disease

The Gruber Lab has three general areas of interest. First, we are interested in the molecules that control differentiation and maturation of ventricular myocytes (after specification). Specialization of ventricular myocytes from compact zone myocytes into trabecular myocytes provides a native system to study the maturation of muscle cells. This is important because 1) morphogenic processes that contribute to some CHD phenotypes are likely dependant upon altered maturation of ventricular myocytes (Shone’s, non-compaction, Type III and IV VSD, and others; and 2) it provides a native system to study the progressive loss of myocyte proliferative capacity from a compact to a trabecular myocytes. We are taking a microgenomic approach to identify novel pathways that control differentiation and maturation of ventricular myocytes. Using the vast clinical resources at CHOP, we have the ability to correlate animal models of congenital heart disease with human disease.

Second, we are interested in uncovering the contribution of epigenetic programs to cardiac development and response to injury. Using a combination of chemical inhibitors and gene-targeted mice, we use a variety of injury and analysis techniques including murine ischemia-reperfusion injury, invasive hemodynamic monitoring, echocardiographic imaging, and, in collaboration with Vic Patel, electrophysiologic techniques to identify signaling pathways that regulate these events.

Third, we are interested in the provenance of cardiac chimerism and the potential contributions of either extracardiac or tissue-derived cardiac progenitor cells in cardiac development and disease. Using murine heterotopic heart transplantation in mice, we use a variety of genetic and imaging techniques to identify signaling pathways that may allow these rare events. We are also working towards the isolation, purification, and complete characterization of human Isl1+ progenitor cells with an eye towards the production of CHD disease-specific cell lines.

Lab Personnel:
Ryan Cobb
Nancy Burnham
Diane Hartman
Jennifer Raue
Courtney Schwalbe
Tao Wang

Lab Contact Information:
905 BRB II/III

421 Curie Boulevard
Philadelphia, PA 19104
office: 215.573.4816
fax: 215.590.2715
website: Gruber Lab

Email: 
pgruber@mail.med.upenn.edu