Howard Young

Ph.D., University of Connecticut
Molecular Biology and Biochemistry     


Department of Biochemistry
Faculty of Medicine & Dentistry
University of Alberta
327 Medical Sciences Building
Edmonton, Alberta, Canada  T6G 2H7 

Tel: 780.492.3931
Lab Tel: 780.492.4577
Fax:  780.492.0886 

Web Site


Inside heart cells, changes in calcium metabolism control the rate and force of muscle contraction and relaxation. With each heart beat, calcium is released from a storage compartment (the ‘sarcoplasmic reticulum’) for muscle contraction and pumped back into the storage compartment for muscle relaxation. Defects in this process are known to be associated with heart failure, and hereditary forms of heart disease may be more common than originally thought. Recently, families suffering from inherited heart disease have been found to have defects at a particular step in calcium metabolism (in proteins called ‘phospholamban’ and ‘sarcolipin’). These defects interfere with the ability of the heart to respond to changes in calcium metabolism, yet we do not fully understand the reason the genetic defects cause heart failure. The premise of our research is that the development of treatments for heart disease requires detailed knowledge of the underlying disease-associated mechanisms. Given the link between phospholamban, sarcolipin and heart failure, a detailed understanding should lead to clinical improvement in patients suffering from heart disease. Our research focuses on detecting new mutations in heart failure patients and understanding the associated molecular defects in calcium metabolism. We focus on phospholamban, sarcolipin and the calcium pump, and how they work together to trigger muscle relaxation. We take the following approaches. We are sequencing the phospholamban and sarcolipin genes in ~1000 University of Alberta heart failure patients. New disease-associated mutations that we identify will be studied using biochemical and structural biology methods. The goal is to develop a detailed molecular understanding of how mutations lead to heart disease. If we can fully understand these details, we may be able to better diagnose and treat patients presenting with heart disease.


Lab Members:

Gareth Armanious, Graduate Student
M'Lynn Fisher, Graduate Student
Muhammad Bashir Khan, Postdoctoral Fellow
Joseph Primeau, Technical

Selected Publications:
Gorski, P.A., Trieber, C.A., Ashrafi, G., Young, H.S. (2015) Regulation of the sarcoplasmic reticulum calcium pump by divergent phospholamban isoforms in zebrafish. Journal of Biological Chemistry 290:6777-88.
Young, H.S., Ceholski, D.K., Trieber, C.A. (2015) Deception in simplicity: Hereditary phospholamban mutations in dilated cardiomyopathy. Biochemistry and Cell Biology 93:1-7.
Abrol, N., Smolin, N., Armanious, G., Ceholski, D.K., Trieber, C.A., Young, H.S., Robia, S.L. (2014) Phospholamban C-terminal residues are critical determinants of the structure and function of the calcium ATPase regulatory complex. Journal of Biological Chemistry289:25855-66.
Muller, M., Kunz, H.H., Schroeder, J., Kemp, G., Young, H.S., Neuhaus, E. (2014) Decreased capacity of sodium import into Arabidopsis chloroplasts impairs salt tolerance, photosynthesis and plant performance. The Plant Journal 78:646-58 (IF 6.6).
Kemp, G., Fliegel, L., Young, H.S. (2014) Membrane Transport Piece by Piece: Production of Transmembrane Peptides for Structural and Functional Studies. Current Protocols in Protein Science Supplement 75, Unit 29.8.
Gorski, P.A., Glaves, J.P., Vangheluwe, P., Young, H.S. (2013) Sarco/endoplasmic reticulum calcium ATPase (SERCA) inhibition by sarcolipin is encoded in its luminal tail. Journal of Biological Chemistry (epub Jan 29).
Smeazzetto, S., Saponaro, A., Young, H.S., Moncelli, M.R., Thiel, G. (2013) Structure-function relation in phospholamban: Modulation of channel activity as a potential regulator of SERCA activity. PLoS One 8(1):e52744
Cortez, M., Kumar, J., Renault, L., Young, H.S., Sim, V.L. (2013) Mouse prion protein polymorphism 108F/189V affects the kinetics of fibril formation and the response to seeding; evidence for a two step nucleation polymerization mechanism. Journal of Biological Chemistry (epub Jan 2)
Glaves, J.P., Gorski, P.A., Alier, K., Ma, L., Primeau, J.O., Jhamandas, J.H., Young, H.S. (2013) Distinct morphological and electrophysiological properties of an elk prion peptide. Peptides 40C:49-56.
Ceholski, D.K., Trieber, C.A., Young, H.S. (2012) Hydrophobic imbalance in the cytoplasmic domain of phospholamban is a determinant for lethal dilated cardiomyopathy. Journal of Biological Chemistry 287:16521-9.
Ceholski, D.K., Trieber, C.A., Holmes, C.F., Young, H.S. (2012) Lethal, hereditary mutants of phospholamban elude phosphorylation by protein kinase A. Journal of Biological Chemistry 287:26596-605.
Gorski, P.A., Trieber, C.A., Larivière, E., Schuermans, M., Wuytack, F., Young, H.S., Vangheluwe, P. (2012) Transmembrane helix 11 is a genuine regulator of the endoplasmic reticulum Ca2+ pump and acts as a functional parallel of β-subunit on α-Na+,K+-ATPase. Journal of Biological Chemistry 287:19876-85.
Chaulk S, Thede GL, Kent OA, Xu Z, Gesner E, Veldhoen RA, Khanna SK, Goping IS, MacMillan AM, Mendell JT, Young HS, Fahlman RP, Glover JNM. (2011). Role of pri-miRNA structure in miR-17~92 biogenesis. RNA Biology 8:1105-14.
Glaves JP, Trieber CA, Ceholski, DK, Stokes DL, Young HS. (2011) Phosphorylation and mutation of phospholamban alter physical interactions with the sarcoplasmic reticulum calcium pump. Journal of Molecular Biology 405:707-23.
Ogawa H, Qiu Y, Huang L, Sam-Chang SW, Young HS, Misono K. (2009) Structure of the atrial natriuretic peptide receptor extracellular domain in the hormone bound and unbound states by single particle electron microscopy. FEBS Journal 276:1347-55.