Graduate Studies Faculty
Zhengfeng Zhou, MD, PhD
Programs:Physiology & Pharmacology
Research Interests:Cardiac Arrhythmia, Potassium channels, Desmosomal proteins, Protein trafficking, RNA processing and stability
Preceptor RotationsDr. Zhou has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. Zhou has not indicated availability as a mentor at this time.
The research in Dr. Zhou’s lab is to study molecular mechanisms of genetic diseases involving cardiac arrhythmias. We are focused on two congenital diseases, long QT syndrome (LQTS) and arrhythmogenic right ventricular dysplasia (ARVD). LQTS is a disease associated with prolonged cardiac action potential duration and prolonged QT intervals on ECG, which can lead to ventricular arrhythmia and sudden death. One of the major forms of LQTS (LQT2) is caused by mutations in the human ether-a-go-go-related gene (hERG) that encodes a voltage-gated potassium channel in the heart. To date, more than 300 hERG mutations have been identified in patients with LQTS. Current studies are investigating the mechanisms of defective protein trafficking of LQT2 mutant channels, and determining how LQT2 mutations lead to defects in splicing and stability of mutant mRNA. ARVD is an inherited disorder characterized by prominent arrhythmias and the replacement of muscle in the heart by fatty tissue. Eight disease-causing genes have been identified in autosomal dominant and recessive forms of ARVD. Most of these genes encode desmosomal proteins including plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. A prominent feature of ARVD mutations is that more than 60% of these mutations are nonsense or frameshift mutations that introduce premature termination codons. The goal of this project is to determine the role of the nonsense-mediated mRNA decay (NMD) pathway in the pathogenesis of ARVD mutations. Understanding how these genetic defects lead to the disease at molecular levels will provide important information directed toward the development of therapeutic strategies for patients with LQTS and ARVD.