Although the neonate heart is completely responsible for delivering blood to the body, it is still immature in many respects.  This is particularly true of the cardiac contractile system and its regulatory mechanisms.  The strength of cardiac contraction is determined by the amount of calcium (Ca2+) delivered to the contractile element.  Thus the levels of Ca2+ inside each cell (or cardiomyocyte) rise and fall each beat, and peak value can vary substantially in response to physiological needs and/or hormones such as adrenaline.  How this is achieved in the neonate heart, although poorly understood, is quite different from the adult heart. This has clinical implications; for example, in children with congenital heart disease (present in 1% of live births), the heart must often be arrested during surgical correction.  However, these techniques are largely derived from our understanding of the adult heart.  We hope to improve the success rate of surgical correction, and better understand “normal” heart development and the deviations that occur in congenital heart diseases.

Molecular mechanisms of electrogenesis in the neonate heart
CIHR funded project focusing on the molecular and cellular mechansms of junctional ectopic tachycardia (JET).  JET is an arrhythmia that occurs with relatively high frequency in neonates after open heart surgery.  The etiology of JET is poorly understood and as a consequence existing treatments are non-specific and often lack efficacy.

Ontogeny of myocardial excitation- contraction coupling mechanisms
CIHR funded project with the objectives of determining the molecular and cellular changes in cardiomyocytes from the earliest stages post-partum until adulthood with an eye to understanding certain congenital heart diseases. 

Regulation of cardiac myofilament sensitivity to calcium
Heart and Stroke Foundation funded project that addresses the structure function relationship of troponin C and its ability to bind Ca2+, a primary determinant of cardiac contractility.  The research involves making mutations of troponin C and understanding how the structural changes that result affect Ca2+ binding to the regulatory domain of the molecule.  Information from this project will be directed to the development of a novel class of Ca2+-senstizing drugs which may be used to treat heart failure.

J Huang, C van Breemen, L Hove-Madsen, and GF Tibbits.  Store-operated Ca2+ entry modulates SR Ca2+ loading in neonatal rabbit cardiac ventricular myocytes.  Circulation Research CIRCRESAHA/2005/101477 – under revision.

TE Gillis, B Liang, F Chung, and GF Tibbits.  Increasing mammalian cardiomyocyte contractility with residues identified in trout troponin C.  Physiological Genomics. 2005 Mar 22; [Epub ahead of print] PMID: 15784699.

CM Marshall, JA Fox, SL Butland, BFF Ouellette, FSL. Brinkman, and GF Tibbits.  Phylogeny of Na+-Ca2+ Exchanger (NCX) genes from genomic data identifies new gene duplications and a new family member in fish species.  Physiological Genomics 2005 Mar 1; [Epub ahead of print] PMID: 15741504.

TMA Blumenschein, TE Gillis, GF Tibbits and BD Sykes.  Effect of temperature on the structure of trout troponin C. Biochemistry 43:4955-63, 2004.

TE Gillis, Tharin MA Blumenschein, BD Sykes, GF Tibbits. Trout cardiac troponin C has intermediate properties between mammalian fast skeletal and cardiac TnCs.  Biochemistry 42: 6418-26, 2003.

S Sett, T Galanopoulos, H Kashihara, DN Talling, JG LeBlanc, GF Tibbits.  Na+/H+ exchange inhibition with HOE 642 improves recovery of the injured neonatal rabbit heart.  Can J Cardiol. 19: 1515-1519, 2003.

Gillis TE, Moyes CD and Tibbits GF.  Sequence mutations in teleost cardiac troponin C that confer high Ca2+ affinity. Am J Physiol 284: C1176-84, 2003.

Marshall C, Elias C, Xue XH, Le HD, Omelchenko A, Hryshko LV, Tibbits GF.  Determinants of cardiac Na+/Ca2+ exchanger temperature dependence: NH2-terminal transmembrane segments. Am J Physiol. 283:C512-20, 2002.

Pauline Dan – Postdoctoral fellow

Tiffany Qu – Lab manager / Postdoctoral fellow

Haruyo Kashihara – Technician

Bo Liang – Technician

Jingbo Huang – PhD student

Eric Lin – PhD student

Christian Marshall – PhD student

Perveen Biln – MSc student

Franca Chung – MSc student

Vivian Hung – MSc student

Caly On – MSc student

Helen Sheng – MSc student