DEPARTMENT OF PHYSIOLOGY
DEPARTMENT OF PHYSIOLOGY
Steven Cala, Ph.D.
Associate Professor of Physiology
and Medicine/Division of Cardiology
Contact Information
Wayne State University
1106 Elliman
421 East Canfield
Detroit, MI 48201Phone: 313-577-8734
FAX: 313-577-8615Email: s.cala@wayne.edu
Education
B.S. in Chemistry - Purdue University
M.S. in Chemistry - Texas A&M University
Ph.D. in Pharmacology - Indiana University
Research Interests
Our laboratory’s research is focused on the cell physiology of the heart cell, and mechanisms of excitation-contraction (E-C) coupling in heart. Our studies involve proteins that regulate release of calcium from the sarcoplasmic reticulum for contraction. One of these proteins is the probable calcium sensor that controls the amount of calcium released at each depolarization. That protein is called calsequestrin. Other proteins of interest include two homologous proteins (triadin and junctin ) that carry the signal from calsequestrin to the SR Ca2+-release channel. We’re investigating the role of these proteins in E-C coupling, studying the interactions between calsequestrin and triadin, and trying to understand how these protein complexes form in heart cells, and how their functions may be altered in disease.
Currently, we are studying how calsequestrin and triadin traffic through the heart cell to concentrate at the Ca2+ release site (Figure). This work stems from our important finding in 2004 that trafficking of calsequestrin is defective in heart failure (see Kiarash et al., below). This may be a crucial event in heart failure, and may explain in part the altered contractile properties of the heart that develops during failure.
Our research is currently funded by the National Heart, Lung, and Blood Institute (NIH/NHLBI), and we have also received funding from the American Heart Association.
Recent Publications
Dutta, K, Carmody, M, Cala, S., Davidoff, A.: Impaired SR Ca2+ uptake without changes in SERCA expression in glucose-induced cardiomyopathy. J. Mol. Cell. Cardiol. 34, 985-996, 2002
O'Brian JJ, Ram ML, Kiarash A, Cala S.: Mass spectrometry of cardiac calsequestrin characterizes microheterogeneity unique to heart and indicative of complex intracellular transit. J. Biol. Chem. 27, 37154-37160, 2002
Vouyouka, A. G., Salib, S. S., Cala, S., Marsh, J.D., and Basson, M.D.: Chronic High Pressure Potentiates the Anti-Proliferative Effect and Abolishes Contractile Phenotypic Changes Caused by Endothelial Cells in Cocultured Smooth Muscle Cells J. Surgical Res. 110, 344-351, 2003.
Kiarash, A., Kelly, C., Phinney, B., Valdivia, H., Abrams, J., and Cala, S.: Defective glycosylation of calsequestrin in heart failure. Cardiovasc. Res. 63, 264-272, 2004.
Houle, T., Ram, M., Cala, S.: Calsequestrin mutant D307H exhibits depressed binding to its protein targets and a depressed response to calcium. Cardiovasc. Res., 64, 227-233, 2004.
Ram, M. Kiarash, A, Marsh, J., Cala, S.: Phosphorylation and dephosphorylation of calsequestrin on CK2- sensitive sites in heart. Molec. Cell. Biochem, 266, 209-217, 2004.
Kelly, C., Ram, M., Francis, S., Cala, S.: Identification of a cytoskeleton-bound form of phospholemman with unique C-terminal immunoreactivity. J. Memb. Biol., 201, 1-9, 2004.
Terentyev, D., Cala, S., Houle, T., Viatchenko-Karpinski, S., Gyorke, I., Terentyeva, R., Williams, S., Gyorke, S.: Triadin overexpression stimulates excitation-contraction coupling and increases predisposition to cellular arrhythmia in cardiac myocytes. Circ. Res. 96, 651-658, 2005.
Wold, L., Dutta, K., Mason, M., Ren, J., Cala, S., Schwanke, M., Davidoff, A.: Impaired SERCA function contributes to cardiomyocyte dysfunction in insulin resistant rats. J. Mol. Cell. Card., 39, 297-307, 2005.
Reis, J., Zhang, L., Cala, S., Jew, K., Mace, L., Chung, L., Moore, R., Ng, Y-C.: Expression of phospholemman in skeletal muscle: effects of aging and exercise training, J. Appl. Physiol., 99, 1508-1515, 2005.
Houle, T., Ram, M., Cala, S.: Different endoplasmic reticulum trafficking and processing pathways for calsequestrin (CSQ) and epitope-tagged CSQ. Exp. Cell Res. 132, 4150-4160, 2006.
Srivastava S, Cala SE, Coetzee WA, Artman M. Phospholemman expression is high in the newborn rabbit heart and declines with postnatal maturation. Biochem. Biophys. Res. Commun. April 6;355(2):338-41, 2007. (Epub 2007 Feb 9).
Milstein ML, McFarland TP, Marsh JD, Cala SE. Inefficient glycosylation leads to high steady-state levels of activity degrading cardiac triadin-1. J. Biol. Chem. Jan 25;283(4):1929-35, 2008. (Epub 2007 Nov 19).
Milstein ML, Houle TD, Cala SE. Calsequestrin isoforms localize to different ER subcompartments: evidence for polymer and heteropolymer-dependent localization. Exp Cell Res. 2009 Feb 1;315(3):523-34. Epub 2008 Nov 25.
This site was created and is maintained by:
Christine Cupps
Updated:
03/13/2009
