Research InterestsMechanisms of dilated cardiomyopathy; Ca2+ regulation in skeletal and cardiac muscle; formation of specialized protein domains in muscle; cardiovascular proteomics.
Keywords: Ca2+ cycling, cardiac muscle, dilated cardiomyopathy, cell biology, proteomics, biomarkers, heart failure.
A major interest of our lab is to investigate the cellular mechanisms involved in the regulation of calcium cycling at the level of sarcoplasmic reticulum and its role in cardiac disease. For these experiments, we apply conventional biochemical and molecular biology assays, digital confocal imaging, and mass spectrometry based proteomic studies. Model systems include: tissue explants, established cell lines, primary cell cultures and transgenic animals. These techniques serve as valuable experimental tools to investigate heart disease pathways, cellular protein sorting and Ca2+ cycling.
Cell and tissue culture: Cardiomyocytes, endothelial cells, smooth muscle cells.
Procedures: Cell biology, confocal imaging, HPLC, gene expression analysis, immunohistochemistry, mass spectrometry, mircoarrays, proteomics, qRT-PCR, RT-PCR, siRNA, transgenic mice, western blot.
Calcium imaging system (Olympus), confocal microscope (Leica LSM IRBE), culture hood, culture incubators, digital microscope (Zeiss structured illumination (SIM), fluorescence microscope, HPLC (Akta), Kodak documentation system, low- and high-speed centrifuge, mass spectrometer (LTQ Orbitrap, TSQ Vantage), plate reader (Perkin Elmer), setups for electropherosis.
Jake Cosme, MSc candidate
Diana Buchsbaum, MSc candidate
Wenping Li, Tech II
Aaron Wilson, Tech II
Dr. Allen Teng, PDF
Dr. Dingyan Wang, research associate
Within the Department of Physiology:
Outside the Department of Physiology:
Gordon Keller, UHN
Peter Liu, UHN
Thomas Kislinger, UHN
Mansoor Husain, UHN
Ian Scott, Sick Kids
Seema Mital, Sick Kids
Robert Hamilton, Sick Kids
Jack Greenblatt, CCBR
Andrew Emili, CCBR
Gary Bader, CCBR
Jason Moffat, CCBR
Igor Stagljar, CCBR
Benoit Bruneau, USCF Gladstone
Publications and Awards
- L.Zhang, X.Chen, M.Nghiem, M.Moon, F.Dawood, M.Chen, P.Sharma, A.O.Gramolini, J.M.Penninger and P.P.Liu (2014) HACE1 maintains cardic cytoskeleton homeostasis by regulating ubiquitin-selective autophagy. Nature Communications 5, 3430
- D.-Y. Wang, C. Abbasi, S. El-Rass, J. Y. Li, F. Dawood, K. Naito, P. Sharma, A. Wilson, S. Yokoe, N. Bousette, X.-Y. Wen, P.P. Liu and A.O. Gramolini. (2014) ERp44 deficiency results in aberrant Ca2+ homeostasis, ER stress-induced apoptosis, and cardiomyopathy. J Am Heart Assoc 3, e001018 . *Article profiled in JAHA.
- V.A. Fajardo, E. Bombardier, C. Vigna, T. Devji, D. Bloemberg, D. Gamu, A.O. Gramolini, J. Quadrilatero, A.R.Tupling (2014) Co-expression of SERCA Isoforms, Phospholamban and Sarcolipin in Human Skeletal Muscle Fibers. PloS One 8, e94304.
- Sun M, Ouzounian M, de Couto G, Chen M, Yan R, Fukuoka M, Li G, Moon M, Liu Y, Gramolini A, Wells GJ, Liu PP Cathepsin-L ameliorates cardiac hypertrophy through activation of the autophagy-lysosomal dependent protein processing pathways..J Am Heart Assoc. 2013 Apr 22;2(2):e000191. doi: 10.1161/JAHA.113.000191.PMID
- P. Sharma, N. U.Nair, W. Li, A. Dong, T. Miyake, A. Wilson, T.Ryan, T. Kislinger, M. Ikura, S.Dhe-Paganon, and A.O.Gramolini (2012) Structural Determination of the Phosphorylation Domain of the Ryanodine Receptor. Fed Euro Biol Soc (FEBS) J 20,3952-64.
- P.J. Rugg-Gunn, B.J. Cox, F. Lanner, P.Sharma, V.Ignatchenko, J.Garner, A.O.Gramolini, J.Rossant and T. Kislinger (2012) Identification of cell-surface proteins enables isolation of viable lineage progenitor cells directly from mouse blastocysts using flow cytometry. Developmental Cell 22,887-901