Biophysics, Cardiovascular, Electrophysiology, Gap Junctions, Gene Therapy, Mathematical and Computational Biology, Mitochondria, Oxidative Stress
Biophysics and Systems Pharmacology [BSP]
BS, Pennsylvania State University
MS, Case Western Reserve University
PhD, Case Western Reserve University
Postdoc, Johns Hopkins University
Summary of Research Focus:
The mission of the Akar Cardiac Bioelectricity Research Laboratory is to uncover the mechanisms underlying sudden cardiac death across a variety of clinically relevant structural heart diseases. We specialize in developing integrative tools that allow us to undertake a systems biology approach to the investigation of arrhythmia mechanisms and to test novel treatment strategies.
We specialize in the use of integrative methodologies for the investigation of electrical disorders, including state-of-the-art imaging technologies for the assessment of electrical heterogeneities across the heart. A major focus of our work is the investigation of abnormalities in impulse formation, conduction, and repolarization using high-resolution optical mapping, and the elucidation of underlying cellular and molecular mechanisms, using electrophysiological, biochemical, and molecular techniques. Specific areas of active research include mechanisms of mechano-electrical feedback, the electrophysiology of mechanical dyssynchrony and resynchronization therapy in canine and porcine models of heart failure, the interaction of myocardial energetics and electrical function in post-ischemic remodeling and reperfusion related arrhythmias, and the role of altered gene expression and targeted gene delivery on ion channel function and arrhythmogenesis in cardiovascular diseases.
Cardiac Bioelectricity Research Laboratory
Grants & Funding:
Xie C, Hu J, Motloch LJ, Karam BS, Akar FG. The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus. Journal of the American College of Cardiology 2015 Sep; 66(10).
Motloch LJ, Hu J, Akar FG. The mitochondrial translocator protein and arrhythmogenesis in ischemic heart disease. Oxidative medicine and cellular longevity 2015; 2015.
Motloch LJ, Akar FG. Gene therapy to restore electrophysiological function in heart failure. Expert opinion on biological therapy 2015 Jun; 15(6).
Karam BS, Akar FG. Blue LEDs get the Nobel Prize while Red LEDs are poised to save lives. Frontiers in physiology 2014; 5.
Xie C, Kauffman J, Akar FG. Functional crosstalk between the mitochondrial PTP and KATP channels determine arrhythmic vulnerability to oxidative stress. Frontiers in physiology 2014; 5.
Kim GE, Ross JL, Xie C, Su KN, Zaha VG, Wu X, Palmeri M, Ashraf M, Akar JG, Russell KS, Akar FG, Young LH. LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation. Cardiovascular research 2015 Oct; 108(1).
Akar FG. A formidable . Heart rhythm : the official journal of the Heart Rhythm Society 2014 Oct; 11(10).
Ishikawa K, Fish KM, Tilemann L, Rapti K, Aguero J, Santos-Gallego CG, Lee A, Karakikes I, Xie C, Akar FG, Shimada YJ, Gwathmey JK, Asokan A, McPhee S, Samulski J, Samulski RJ, Sigg DC, Weber T, Kranias EG, Hajjar RJ. Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure. Molecular therapy : the journal of the American Society of Gene Therapy 2014 Dec; 22(12).
Xie C, Biary N, Tocchetti CG, Aon MA, Paolocci N, Kauffman J, Akar FG. Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs. American journal of physiology. Heart and circulatory physiology 2013 Apr; 304(7).
Akar FG. Mitochondrial targets for arrhythmia suppression: is there a role for pharmacological intervention?. Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing 2013 Sep; 37(3).
Turnbull IC, Karakikes I, Serrao GW, Backeris P, Lee JJ, Xie C, Senyei G, Gordon RE, Li RA, Akar FG, Hajjar RJ, Hulot JS, Costa KD. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2014 Feb; 28(2).
Akar FG. Emergence of atrial repolarization alternans at late stages of remodeling: the . Journal of cardiovascular electrophysiology 2014 Apr; 25(4).
Akar FG, Hajjar RJ. Gene therapies for arrhythmias in heart failure. Pflügers Archiv : European journal of physiology 2014 Jun; 466(6).
Nederlof R, Xie C, Eerbeek O, Koeman A, Milstein DM, Hollmann MW, Mik EG, Warley A, Southworth R, Akar FG, Zuurbier CJ. Pathophysiological consequences of TAT-HKII peptide administration are independent of impaired vascular function and ensuing ischemia. Circulation research 2013 Jan; 112(2).
Chaanine AH, Nonnenmacher M, Kohlbrenner E, Jin D, Kovacic JC, Akar FG, Hajjar RJ, Weber T. Effect of bortezomib on the efficacy of AAV9.SERCA2a treatment to preserve cardiac function in a rat pressure-overload model of heart failure. Gene therapy 2014 Apr; 21(4).
Karam CS, Akar FG. Genetic silencing of pacemaker cells: local intervention with global implications. Journal of the American Heart Association 2012 Apr; 1(2).
Akar FG, Clancy CE. Arrhythmia models: in vivo, in vitro and in silico. Drug discovery today. Disease models 2009; 6(3).
Akar FG, O'Rourke B. Mitochondria are sources of metabolic sink and arrhythmias. Pharmacology & therapeutics 2011 Sep; 131(3).
Smeele KM, Southworth R, Wu R, Xie C, Nederlof R, Warley A, Nelson JK, van Horssen P, van den Wijngaard JP, Heikkinen S, Laakso M, Koeman A, Siebes M, Eerbeek O, Akar FG, Ardehali H, Hollmann MW, Zuurbier CJ. Disruption of hexokinase II-mitochondrial binding blocks ischemic preconditioning and causes rapid cardiac necrosis. Circulation research 2011 May; 108(10).
Salama G, Akar FG. Deciphering Arrhythmia Mechanisms - Tools of the Trade. Cardiac electrophysiology clinics 2011 Mar; 3(1).
Biary N, Xie C, Kauffman J, Akar FG. Biophysical properties and functional consequences of reactive oxygen species (ROS)-induced ROS release in intact myocardium. The Journal of physiology 2011 Nov; 589(Pt 21).
Tocchetti CG, Caceres V, Stanley BA, Xie C, Shi S, Watson WH, O'Rourke B, Spadari-Bratfisch RC, Cortassa S, Akar FG, Paolocci N, Aon MA. GSH or palmitate preserves mitochondrial energetic/redox balance, preventing mechanical dysfunction in metabolically challenged myocytes/hearts from type 2 diabetic mice. Diabetes 2012 Dec; 61(12).
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