Jifen Li, MD, PhD
Philadelphia, PA 19107
(215) 503-5731 fax
Most Recent Peer-reviewed Publications
- 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
- 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
M.D. Pediatrics, TongJi Medical University, Hubei, China
Cardiovascular and Molecular Biology, University of Pennsylvania School of Medicine, Philadelphia, PA
Ph.D. Molecular Biology/Virology, Tokyo Medical and Dental University, Tokyo, Japan
Instructor of Medicine, 2007
Research and Clinical Interests
My current research interests focus on the molecular mechanism underlying arrhythmogenic right ventricular cardiomyopathy (ARVC) and how disregulation of N-cadherin, and its cytoplasmic binding proteins, catenins contributes to arrhythmogenesis. ARVC is an inherited heart muscle disease responsible for approximately 5% of unexplained sudden cardiac death (SCD) cases in young athletes in the United States. The main clinical features are right ventricular fibro-fatty replacement of cardiac muscle cells, arrhythmias and SCD.
Intercalated disc (ICD) is a specialized structure connecting cardiomyocytes at their termini that contains three types of intercellular junctions: adherens junctions, desmosomes, and gap junctions. Intercalated discs support synchronized contraction of cardiac tissue. Genetic studies have identified mutations in various components of desmosomes in ARVC patients; hence ARVC is often referred to as a disease of the desmosome.
N-cadherin is a cell adhesion molecule that glues cells together. We recently reported that total loss of N-cadherin in the adult mouse heart results in complete dissolution of the intercalated disc structure and moderate dilated cardiomyopathy. Altered cell-cell communication between the muscle cells is responsible for the sudden arrhythmic death phenotype. By genetically manipulating the levels of N-cadherin/Cx43 in mice, we discovered that size of the Cx43-containing plaques was more important than the total number of plaques in maintaining the normal rhythm of the heart.
I have extended my research focus into the role of the cadherin associated proteins, plakoglobin (PKG) and aT-catenin in the molecular pathogenesis of ARVC. Plakoglobin, also known as y-catenin, is the only catenin found in both adherens junctions and desmosomes. By competing with ß-catenin, PKG is also known to inhibit Wnt/ß-catenin signaling pathway and subsequently enhance adipocyte differentiation. AlphaT-catenins are cytoplasmic proteins that link cadherins to cytoskeleton. AlphaT-catenin is a recently identified a-catenin isoform thought to provide additional adhesive strength in the heart by interacting with a desmosome protein. We expect that disruption of the cadherin/catenin linkage between the myocytes will impair ICD structure, alter Wnt/ß-catenin signaling, and recapitulate the ARVC phenotype.
The long term goal of my research is to determine the specific contribution of altered cell-cell interactions in cardiovascular disease. Understanding of how cadherin/catenin regulates rhythmic contraction of the heart may help to identify genetic risk factors in sudden cardiac death patients and should eventually contribute to development of novel anti-arrhythmic therapies.