Glenn Radice, PhD
Philadelphia, PA 19107
(215) 503-5731 fax
Most Recent Peer-reviewed Publications
- N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility
- N-cadherin is required for neural crest remodeling of the cardiac outflow tract
- Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis
- N-cadherin acts upstream of VE-cadherin in controlling vascular morphogenesis
- Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure
Columbia University, New York, NY
Kyoto University, Department of Biophysics, Kyoto, Japan Massachusetts Institute of Technology, Center for Cancer Research, Cambridge, MA
Ph.D. Columbia University, 1990
Associate Professor of Medicine (2007)
Research and Clinical Interests
The Radice laboratory investigates the function of cadherins, a family of cell adhesion molecules, critical for the establishment and maintenance of tissue structure. Classical cadherins are Ca2+-dependent homophilic cell adhesion molecules concentrated at cell-cell contact sites called adherens junctions. Its cytoplasmic binding partners, the catenins, mediate linkage of the cadherin to the actin cytoskeleton and regulate its adhesive activity. Abnormal tissue architecture is associated with many forms of disease including cardiomyopathy and cancer. The lab's research focuses on the role of the N-cadherin/catenin complex in maintaining mechanical and electrical coupling between cardiomyocytes in the working heart. To do this, we utilize novel genetically engineered mouse models to ablate specific components of the adhesion complex in the adult heart. We have shown that the N-cadherin/catenin complex is critical for maintaining normal heart rhythms and that loss of the adhesion complex leads to sudden arrhythmic death. Sudden cardiac death in this model is attributed, at least in part, to decreased ventricular conduction velocity due to gap junction remodeling. We hypothesize that aberrant cadherin/catenin function affects gap junction stability leading to arrhythmogenesis in patients suffering from many forms of heart disease including hypertrophy, ischemia, and dilated cardiomyopathies. Knowledge gained from our research will provide a molecular framework for understanding the mechanism of arrhythmogenesis in heart disease. In turn our studies may lead to better screening methods to identify persons at risk of sudden death due to cardiac arrhythmia and possibly to novel therapies.
Changes in cell-cell and cell-matrix adhesion accompany the transition from benign tumors to invasive, malignant cancer and the subsequent metastatic dissemination of tumor cells. Cadherin switching (E- to N-cadherin) is a hallmark of tumor progression, yet it is poorly understood how N-cadherin affects tumor cell behavior in vivo. We have initiated a new research program in the lab to determine N-cadherin's role in pancreatic cancer progression.