Basic Science Research

Our physician-scientists are using a combination of human and animal genetic model systems to unravel the genetic mechanisms of congenital heart disease, with the ultimate aim of improving therapies and preventive strategies. They are exploring molecular mechanisms of heart failure, using induced pluripotent stem cell technology for cardiovascular studies and tissue engineering and studying the molecular mechanisms by which biomechanical forces stimulate ventricular growth.

In Dr. Paul Grossfeld’s laboratory, scientists use genetically engineered mouse models to study the mechanisms of how loss of ETS-1 causes congenital heart defects. Specifically, his lab has recently found that conditional deletion of ETS-1 in the neural crest causes ventricular septal defects, the most common congenital heart defect in Jacobsen syndrome, through a cell autonomous mechanism.  His lab has now accumulated evidence for a single genetic modifier locus in a mouse that can prevent the development of congenital heart defects in the absence of ETS-1. Through his collaboration with Dr. Marianne Bronner and Dr. Shuyi Nie, he has developed an animal model for hypoplastic left heart syndrome. Preliminary studies have identified a putative signaling pathway that is affected by the loss of ETS-1 and that the HLHS phenotype can be rescued by grafting normal progenitor heart cells early in heart development.

Dr. Grossfeld has also extended his studies to understanding the genetic basis of intellectual disability and behavioral problems. This research has led to the identification of several disease-causing genes, which have now provided the basis for gene-based therapeutic clinical trials. Dr. Grossfeld also serves as the cardiology consultant for U.S. volleyball.  This involves the development of a comprehensive screening program for the athletes and has led to the recent identification of a previously undiagnosed team member with Marfan syndrome and a life-threatening aortopathy.