Protein Expression Profiling for Heart Disease Biomarker Discovery
Website: www.utoronto.ca/heartproject/
Summary
Heart disease is the number-one killer of Canadians. While most people associate heart disease with heart attacks, a new epidemic involves the more insidious heart failure. The latter occurs when damage over time weakens the muscle so that finally the organ cannot pump enough blood to all parts of the body to support normal activities. People with late-stage heart failure can barely walk up one flight of stairs, after which they gasp for breath and feel like they are drowning.
Dr. Peter Liu of the University of Toronto led a team of researchers in the “Protein Expression Profiling for Heart Disease Biomarker Discovery” project to discover molecular biomarkers in the blood to identify patients with early-stage heart failure or at risk for the condition.
The project team consisted of experts in cardiovascular science and proteomics research at the University of Toronto. Dr. Andrew Emili is a world renowned expert in the new science of proteomics exploring unique protein patterns in health and disease. Dr. David MacLennan is an international authority on the pathways leading to heart failure, and Dr. Anthony Gramolini uses advanced genomics and proteomics tools to investigate the physiology and biochemistry of membrane proteins. As a result of the three-year project, the team identified several unique protein markers for heart failure by comparing changes in the proteomes of heart tissue from patients suffering from heart failure with those with normal, healthy hearts. Working with Roche Diagnostics GmbH, the project team is further validating these diagnostic and prognostics biomarkers with the ultimate goal of developing a simple blood test with which physicians can screen for early forms of heart disease and thereby slow the emerging tide of sufferers.
Notable Publications
Gramolini, AO, Kislinger, T, Alikhani-Koopaei, R, Fong, V, Thompson, NJ, Isserlin, R, Sharma, P, Oudit, GY, Trivieri, MG, Fagan, A, Kannan, A, Higgins, DG, Huedig, H, Hess, G, Arab, S, Seidman, JG, Seidman, CE, Frey, B, Perry, M, Backx, PH, Liu, PP, MacLennan, DH, Emili, A. 2007. Comparative proteomics profiling of a phospholamban mutant mouse model of dilated cardiomyopathy reveals progressive intracellular stress responses. Mol Cell Proteomics 7(3): 519-33.
Musso, GA, Zhang, Z, Emili, A. 2007. Experimental and computational procedures for the assessment of protein complexes on a genome-wide scale. Chem Rev 107(8): 3585-600.
Musso, GA, Zhang, Z, Emili, A. 2007. Retention of protein complex membership by ancient duplicated gene products in budding yeast. Trends Genet 23(6): 266-9.
Cox, B, Kislinger, T, Wigle, DA, Kannan, A, Brown, K, Okubo, T, Hogan, B, Jurisica, I, Frey, B, Rossant, J, Emili, A. 2007. Integrated proteomic and transcriptomic profiling of mouse lung development and Nmyc target genes. Mol Syst Biol 3: 109.
Kislinger T, Cox B, Kannan A, Chung C, Hu P, Ignatchenko A, Scott MS, Gramolini AO, Morris Q, Hallett MT, Rossant J, Hughes TR, Frey B and Emili A. 2006. Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling. Cell 125(1):173-86.
Cox B and Emili A, 2006. Tissue subcellular fractionation and protein extraction for use in mass-spectrometry-based proteomics. Nat Protoc 1(4):1872-8.
Kislinger T, Gramolini AO, Pan Y, Rahman K, MacLennan DH, and Emili A. 2005. Proteome dynamics during C2C12 myoblast differentiation. Mol Cell Proteomics 4(7):887-901.
Pan Y, Kislinger T, Gramolini AO, Zvaritch E, Kranias EG, MacLennan DH, and Emili A. 2004. Identification of biochemical adaptations in hyper- or hypocontractile hearts from phospholamban mutant mice by expression proteomics. Proc Natl Acad Sci USA 101(8):2241-6.
