Elod Szabo

Research Synopsis

Dr. Szabo’s research interest focuses on the cellular mechanism of dilated cardiomyopathy (DCM) as it relates to intracellular ion homeostasis. Recent development in genetics have linked mutations in the cardiac voltage-gated Na channel (Nav1.5) to familial DCM. Such mutations cluster in the evolutionary conserved voltage-sensing region (S4) of the channel. Perturbation of the complex structure of S4 can cause a non-selective leak current as demonstrated in structure-function studies of K channels and certain mutant skeletal muscle Na channels. Based on structural parallels of Nav1.5 DCM mutants and the various channels exhibiting such a leak current, Dr. Szabo believes that the underlying mechanism of Nav1.5-related cardiomyopathy is the presence of a leak current through the voltage gating pore. Indiscriminate cationic current originating from the passage of ions through a hole formed in the gating pore can disturb intracellular ion homeostasis culminating in changes in intracellular Ca concentration, ultimately interfering with contraction-relaxation mechanism of cardiomyocytes. To test this hypothesis, he has developed a knock-in mouse-model of Nav-related DCM. Analysis of the model is under way. 

Recent Publications

1. Jinadasa T, Szabo EZ, Numata M, Orlowski J. Activation of AMP-activated Protein Kinase Regulates Hippocampal Neuronal pH by Recruiting Na+/H+ Exchanger NHE5 to the Cell Surface. The Journal of Biological Chemistry. 2014 Jun 16.
2. Nair K, Pekhletski R, Harris L, Care M, Morel C, Farid T, Backx PH, Szabo E, Nanthakumar K. Escape capture bigeminy: Phenotypic marker of cardiac sodium channel voltage sensor mutation R222Q. Heart Rhythm. Heart Rhythm 2012 Oct; 9(10):1681-8.ei doi:10.1016/j.hrthm.2016.06.029. Epub2012 Jun16. 2nd Senior Author.
3. V. Lukashova, E.Z. Szabó, T. Jinadasa, A. Mokhov, D. Litchfield, J. Orlowski. CK2 phosphorylation of an acidic Ser/Thr di-isoleucine motif in Na+/H+ exchanger NHE5 isoform promotes association with β-arrestin2 and endocytosis. The Journal of Biological Chemistry. J Biol Chem. 2011 Apr 1; 286(13) 11456-68.
4. E.Z. Szabó, I. Luginbuehl, B. Bissonnette. Impact of anesthetic agents on cerebrovascular physiology in children. Review. Paedriatic Anesthesia. Paedriatic Anaesth. 2009 Jan; 19(2):108-18. Principal Author.
5. E.Z. Szabó, M. Numata, V. Lukashova, P. Iannuzzi, J. Orlowski. beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform. Proc Natl Acad Sci USA. 2005 Feb; 102(8):2790-5. Principal Author.

Honours and Awards

2015

2012-2013