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Eric A. Sobie

ASSISTANT PROFESSOR  Pharmacology and Systems Therapeutics

Overview

Gender Male
E-mail eric.sobie@mssm.edu
Education and Training Ph.D., The Johns Hopkins University School of Medicine
  B.S.E., Duke University
  Postdoctoral Fellowship, University of Maryland
Awards 2008
Dr. Harold and Golden Lamport Research Award
Mount Sinai School of Medicine

Sobie Laboratory

Training

Education and Training Ph.D., The Johns Hopkins University School of Medicine
  B.S.E., Duke University
  Postdoctoral Fellowship, University of Maryland

Research

Specific Clinical/Research Interest:
Coupling of experiments and computational modeling to understand interactions between electrical and calcium signaling systems in ventricular myocytes

Current Students: Amrita Sarkar, Rushita Patel

Postdoctoral Fellows: Hena Ramay, Young-Seon Lee

Research Personnel: Frank Fabris

The Sobie Laboratory is focused on increasing our fundamental understanding of how calcium signaling in heart cells interacts with and influences the heart's electrical and mechanical function. By combining state-of-the-art experimental techniques with computational modeling, the work provides insight into the regulation of normal heart function as well as how this regulation may be altered in pathological states such as heart failure.

Effective pumping of blood by the heart depends on complex interactions between electrical and calcium signaling systems within heart cells. Each time the heart beats, current flowing through the ion channels in the plasma membrane changes the voltage across the cell membrane. This induces the opening of channels selective for calcium, which allow calcium ions to enter the cell. These calcium ions in turn causes the release of a much larger amount of calcium from intracellular stores. This process, known as calcium-induced calcium release is the key event linking electrical excitation to contraction of the heart. Mis-regulation of this process can contribute to pathological function in disease states such as heart failure, but the precise molecular defects that cause particular clinical observations are not well-understood. Thus, studies that produce a more thorough, quantitative understanding of calcium handling in the heart may lead to the identification of new targets for therapies. Several projects underway in the laboratory are aimed at understanding the regulation of calcium-induced calcium release and the interactions between electrical and calcium signals in heart cells.

Keywords: Biophysics, Calcium, Computer Simulation, Electrophysiology, Heart, Mathematical and Computational Biology, Systems Biology

Current Research Studies:
2005-2010: Ensemble Density Analysis for Stochastic Models of Cardiac Excitation-Contraction Coupling. National Science Foundation 0443843.  Collaboration with Dr.'s Saleet Jafri of George Mason University and Gregory D. Smith of the College of William and Mary.

2005-2010: Control of local calcium signaling in the heart; National Institutes of Health R01 HL RHL076230A; The goals of this project are to investigate how changes in the trigger for calcium release in heart cells influence the gain of excitation contraction coupling and to examine the mechanisms underlying the recovery of calcium release after termination.

2007-2012Systems Biology Center in New York.  National Institutes of Health P50 GM071558-01; Dr. Sobie leads one of the projects in this multi-investigator grant.  The center is headed by Dr. Ravi Iyengar.

Publications

Sobie EA. Parameter sensitivity analysis in electrophysiological models using multivariable regression. Biophysical Journal;: in press.


Williams GB, Huertas MA, Sobie EA, Jafri MS, Smith GD. Moment closure for local control models of calcium-induced calcium release in cardiac myocytes. Biophysical Journal 2008;: 1689-1703.


Wang LJ, Sobie EA. Mathematical model of the neonatal mouse action potential. American Journal of Physiology 2008; 294: H2565-H2575.


Sobie EA, Cannell MB, Bridge JB. Allosteric activation of Na+-Ca2+ exchange by L-type Ca2+ current augments the trigger flux for SR Ca2+ release in ventricular myocytes. Biophysical Journal 2008; 94: L54-L56.


Sobie EA, Kao JP, Lederer WJ. Novel approach to real-time flash photolysis and confocal [Ca(2+)] imaging. Pflugers Arch: European Journal of Physiology 2007 July; 454(4): 663-673.


Collis LP, Meyers MB, Zhang J, Phoon CK, Sobie EA, Coetzee WA, Fishman GI. Expression of a sorcin missense mutation in the heart modulates excitation-contraction coupling. FASEB J 2007; 21(2): 475-487.


Song LS, Sobie EA, Mcculle S, Lederer WJ, Balke CW, Cheng H. Orphaned ryanodine receptors in the failing heart. Proc Natl Acad Sci U S A 2006 Mar 14; 103(11): 4305-4310.


Sobie EA, Guatimosim S, Gomez-Viquez L, Song LS, Hartmann H, Saleet Jafri M, Lederer WJ. The Ca 2+ leak paradox and rogue ryanodine receptors: SR Ca 2+ efflux theory and practice. Prog Biophys Mol Biol 2006; 90: 172-185.


Sobie EA, Song LS, Lederer WJ. Local recovery of Ca2+ release in rat ventricular myocytes. J Physiol 2005 Jun; 565(Pt 2): 441-447.


Sobie EA, Dilly KW, Cruz JS, Lederer WJ, Jafri MS. Termination of cardiac Ca2+ sparks: an investigative mathematical model of calcium-induced calcium release. Biophysical Journal 2002; 83: 59-78.


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