Thomas Jefferson University
Sidney Kimmel Medical College
Department of Medicine

Li, Jifen

< Back


Jifen Li

Jifen Li, MD, PhD

Contact Dr. Li

1020 Locust Street
Room 543G
Philadelphia, PA 19107

(215) 503-8262
(215) 503-5731 fax

Medical School

MD Pediatrics, TongJi Medical University, Hubei, China
PhD Molecular Biology/Virology, Tokyo Medical and Dental University, Tokyo, Japan


Cardiovascular and Molecular Biology, University of Pennsylvania School of Medicine, Philadelphia, PA

University Appointment

Instructor of Medicine, 2007

Research & 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.


Most Recent Peer-Reviewed Publications

  1. Alpha-catenins control cardiomyocyte proliferation by regulating yap activity
  2. Beyond cell adhesion: The role of armadillo proteins in the heart
  3. N-cadherin haploinsufficiency increases survival in a mouse model of pancreatic cancer
  4. Analysis of a Jup hypomorphic allele reveals a critical threshold for postnatal viability
  5. Loss of cadherin-binding proteins β-catenin and plakoglobin in the heart leads to gap junction remodeling and arrhythmogenesis
  6. Loss of αT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia
  7. Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of β-catenin signaling
  8. Effects of cardiac-restricted overexpression of the A2A adenosine receptor on adriamycin-induced cardiotoxicity
  9. Phospholemman and β-adrenergic stimulation in the heart
  10. A new perspective on intercalated disc organization: Implications for heart disease
  11. Scavenger receptor B2 is a cellular receptor for enterovirus 71
  12. N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility
  13. Dysregulation of cell adhesion proteins and cardiac arrhythmogenesis
  14. Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis
  15. IL-27 subunits and its receptor (WSX-1) mRNAs are markedly up-regulated in inflammatory cells in the CNS during experimental autoimmune encephalomyelitis
  16. Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure
  17. T cell and antibody responses in remitting-relapsing experimental autoimmune encephalomyelitis in (C57BL/6 x SJL) F1 mice
  18. Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia
  19. Role of IL-12 Receptor β1 in Regulation of T Cell Response by APC in Experimental Autoimmune Encephalomyelitis
  20. Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-β2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system