522 First Avenue
New York, NY 10016
My laboratory focuses on several facets of cardiovascular biology and disease. First, we are interested in the formation and function of the heart's specialized cardiac conduction system (CCS). This complex network comprises pacemaking cells that establish the normal rhythmicity of the heart, as well as rapidly conducting His-Purkinje cells that facilitate highly synchronized excitation of the working myocardium.
Our studies of the conduction system utilize genetically engineered mouse models that specifically visualize various components of the network. Gene profiling of microdissected CCS tissue is then employed to identify the molecular signature of these specialized cells. A complementary approach for gene discovery using murine embryonic stem cells is being developed, whereby such pluripotent cells can be differentiated into specific components of the CCS under defined cultured conditions.
A second area of investigation includes studies of arrhythmia mechanisms, focusing especially on the dysregulation of gap junction channels and the associated abnormalities in impulse propagation. These studies include a multiple of strategies that range from molecular and biochemical through genetically engineered murine models with site-specific mutations in connexin genes, which encode the gap junction channel proteins. Our laboratory was the first to demonstrate the essential role of gap junction channels in cardiac rhythmicity, using conditional knockout approaches. Current studies are focused on defining the role of post-translational regulation of connexins during normal gap junction formation and in response to pathologic stimuli that lead to abnormal gap junction remodeling.
Purkinje Cells as Sources of Arrhythmias in Long QT Syndrome Type 3
Iyer, Vivek; Roman-Campos, Danilo; Sampson, Kevin J; Kang, Guoxin; Fishman, Glenn I; Kass, Robert S. Purkinje Cells as Sources of Arrhythmias in Long QT Syndrome Type 3. Scientific reports. 2015 Aug 20;5:13287-13287 (1732302)
Isolation and Characterization of ESC-Derived Cardiac Purkinje Cells
Maass, Karen; Shekhar, Akshay; Lu, Jia; Kang, Guoxin; See, Fiona; Kim, Eugene; Delgado, Camila; Shen, Steven; Cohen, Lisa; Fishman, Glenn I. Isolation and Characterization of ESC-Derived Cardiac Purkinje Cells. Stem cells. 2015 Apr ;33(4):1102-1112 (1411522)
Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias
Park, David S; Cerrone, Marina; Morley, Gregory; Vasquez, Carolina; Fowler, Steven; Liu, Nian; Bernstein, Scott A; Liu, Fang-Yu; Zhang, Jie; Rogers, Christopher S; Priori, Silvia G; Chinitz, Larry A; Fishman, Glenn I. Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias. Journal of clinical investigation. 2015 Jan;125(1):403-412 (1410832)
Efficient Generation of Cardiac Purkinje Cells from ESCs by Activating cAMP Signaling
Tsai, Su-Yi; Maass, Karen; Lu, Jia; Fishman, Glenn I; Chen, Shuibing; Evans, Todd. Efficient Generation of Cardiac Purkinje Cells from ESCs by Activating cAMP Signaling. Stem cell reports. 2015 May 28;4(6):1089-1102 (1615182)
Efficient Generation of Cardiac Purkinje Fiber-like Cells From ESCs by Activating cAMP Signaling
Tsai, Su-Yi; Maass, Karen; Lu, Jia; Fishman, Glenn I; Chen, Shuibing; Evans, Todd. Efficient Generation of Cardiac Purkinje Fiber-like Cells From ESCs by Activating cAMP Signaling [Meeting Abstract]. Circulation research. 2015 JUL 17;117:?-? (2118992)