Glenn Radice, PhD
Philadelphia, PA 19107
(215) 503-5731 fax
Columbia University, New York, NY
PhD Columbia University, 1990
Kyoto University, Department of Biophysics, Kyoto, Japan Massachusetts Institute of Technology, Center for Cancer Research, Cambridge, MA
Associate Professor of Medicine (2007)
Research & Clinical Interests
The Radice laboratory is interested in understanding molecular mechanisms of cardiovascular development and physiology and their implications for human disease. Cadherins form intercellular junctions, which serve both as mechanical linkages between cells and as signaling hubs that modulate intracellular signal transduction. Transgenic and knockout mouse models are used to investigate the function of the N-cadherin/catenin cell adhesion complex in embryonic, fetal and 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 death in this model is attributed to gap junction remodeling that leads to decreased ventricular conduction velocity and re-entrant arrhythmias. The role of g-catenin or plakoglobin in the etiology of arrhythmogenic cardiomyopathy is currently under investigation.
More recent work focuses on the role of the cytoskeletal linker proteins, a-catenins, in cardiac development and regeneration. We discovered that ablating a-catenins stimulates cardiomyocyte proliferation by allowing Yap, a transcriptional co-activator, to accumulate in the nucleus where it binds to TEAD transcriptional factors to induce expression of cell cycle regulators and other target genes. In preclinical studies, a-catenin mutant mice exhibit enhanced cardiomyocyte proliferation and improved contractility following myocardial infarction. We are currently investigating whether cytoskeletal remodeling regulates Yap cellular distribution in a-catenin-deficient cardiomyocytes.
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 shown that interfering with N-cadherin is sufficient to prolong survival of mice suffering from highly metastatic pancreatic cancer.
Opportunities are available to analyze transgenic and knockout mice that serve as models of human disease. Specific projects involve the investigation of a-catenins in cardiac regeneration, plakoglobin in arrhythmogenic cardiomyopathy, and N-cadherin in pancreatic cancer metastasis. Projects are tailored to students’ experience and interest.
Most Recent Peer-Reviewed Publications
- Niche Cadherins Control the Quiescence-to-Activation Transition in Muscle Stem Cells
- N-cadherin regulates signaling mechanisms required for lens fiber cell elongation and lens morphogenesis
- N-cadherin functions as a growth suppressor in a model of K-ras-induced PanIN
- New functions for alpha-catenins in health and disease: from cancer to heart regeneration
- Alpha-catenins control cardiomyocyte proliferation by regulating yap activity
- N-cadherin induction by ECM stiffness and FAK overrides the spreading requirement for proliferation of vascular smooth muscle cells
- N-cadherin/catenin complex as a master regulator of intercalated disc function
- Calorie restriction delays the progression of lesions to pancreatic cancer in the LSL-KrasG12D; Pdx-1/Cre mouse model of pancreatic cancer
- N-Cadherin-mediated adhesion and signaling from development to disease: Lessons from mice
- Beyond cell adhesion: The role of armadillo proteins in the heart
- N-cadherin haploinsufficiency increases survival in a mouse model of pancreatic cancer
- Analysis of a Jup hypomorphic allele reveals a critical threshold for postnatal viability
- N-cadherin and β1-integrins cooperate during the development of the enteric nervous system
- Loss of cadherin-binding proteins β-catenin and plakoglobin in the heart leads to gap junction remodeling and arrhythmogenesis
- Loss of αT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia
- Requirement for N-cadherin-catenin complex in heart development
- Cortactin is required for N-cadherin regulation of Kv1.5 channel function
- Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of β-catenin signaling
- N-cadherin and cadherin 11 modulate postnatal bone growth and osteoblast differentiation by distinct mechanisms
- Persistence of coordinated long-term potentiation and dendritic spine enlargement at mature hippocampal CA1 synapses requires N-cadherin