• Integrative Physiology

    Integrative Physiology

    The study of the acute and chronic effects of exercise and influence of physical training and nutrition

Vladimir Ljubicic
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Associate Professor; Canada Research Chair (Tier 2) in Neuromuscular Plasticity in Health and Disease
Ivor Wynne Centre, Room E207
905 525 9140 ext. 24517
Neuromuscular plasticity refers to the remodeling of the neuromuscular system in response to genetic or environmental cues. Neuromuscular disorders, including the neuromuscular alterations that are hallmarks of advanced aging, are more common in Canada then generally appreciated. The central experimental questions that form the foundation of our research program are: 1) What roles do phenotype-modifying proteins play in the maintenance and remodeling of the peripheral neuromuscular system, and 2) Are these molecules efficacious therapeutic targets for neuromuscular disorders? To address these questions, we design investigations around rational lifestyle- and pharmacological-based strategies focused on the manipulation of powerful phenotype-bending molecules in the neuromuscular system. Furthermore, we employ an integrative and rigorous cell-to-animal experimental approach, as well as an innovative combination of molecular physiological solutions. The long-term goal of our research is to expand fundamental understanding of the mechanisms governing neuromuscular plasticity, as well as to identify novel, evidence-based therapeutic strategies to improve the lives of those with compromised neuromuscular systems.

Neuromuscular exercise biology; Duchenne muscular dystrophy; Spinal muscular atrophy; Myotonic dystrophy type 1; Sarcopenia of aging; AMP-activated protein kinase; Protein arginine methyltransferases


Course Code
  Course Name
KINESIOL 3Z03   Neuromuscular Plasticity in Health and Disease


Course Code
  Course Name
KIN 728   Integrative Cell and Molecular Exercise Physiology

* indicates graduate students under my supervision, # indicates undergraduate students under my supervision, ^ indicates graduate students under my co-supervision.

*Ng SY, *Manta A, Ljubicic V. Exercise Biology of Neuromuscular Disorders. Appl Physiol Nutr Metab. In press.

*Dial AG, *Ng SY, *Manta A, Ljubicic V. The Role of AMPK in Neuromuscular Biology and Disease. Trends Endocrinol Metab. 29:300-312, 2018.

*Dial AG, #Rooprai P, Lally JS, Bujak AL, Steinberg GR, Ljubicic V. The role of AMP-activated protein kinase in the expression of the dystrophin-associated protein complex in skeletal muscle. FASEB J. 32:2950-65, 2018.

*Shen NY, *Ng SY, #Toepp S, Ljubicic V. Protein arginine methyltransferase expression and activity during myogenesis. Biosci Rep. 38:1-17, 2018.

*vanLieshout TL, *Stouth DW, #Tajik T, Ljubicic V. Exercise-induced Protein Arginine Methyltransferase Expression in Skeletal Muscle. Med Sci Sports Exerc. 50:447-457, 2018.

*Stouth DW, *Manta A, Ljubicic V. Protein arginine methyltransferase expression, localization, and activity during disuse-induced skeletal muscle plasticity. Am J Physiol Cell Physiol. 314:C177-190, 2018.

*Stouth DW, *vanLieshout TL, *Shen NY, Ljubicic V. Regulation of Skeletal Muscle Plasticity by Protein Arginine Methyltransferases and Their Potential Roles in Neuromuscular Disorders. Front Physiol. 8:870, 2017.

Péladeau C, ^Ahmed A, Amirouche A, Crawford TE, Bronicki LM, Ljubicic V, Renaud JM, Jasmin BJ. Combinatorial Therapeutic Activation with Heparin and AICAR Stimulates Additive Effects on Utrophin A Expression in Dystrophic Muscles. Hum Mol Genet. 25:24-43, 2016.

Ljubicic V, Jasmin BJ. Metformin increases PGC-1α and utrophin A expression in dystrophic skeletal muscle. Muscle Nerve 52:139-42, 2015.

^Al-Rewashdy H, Ljubicic V, Lin W, Renaud JM, Jasmin BJ. Utrophin A is Essential in Mediating the Functional Adaptations of mdx Mouse Muscle Following Chronic AMPK Activation. Hum Mol Genet. 24:1243-55, 2015.

Zhang Y, Uguccioni G, Ljubicic V, Irrcher I, Iqbal S, Singh K, Ding S, Hood DA. Multiple signaling pathways regulate contractile activity-mediated PGC-1α gene expression and activity in skeletal muscle cells. Physiol Rep. 2:e12008, 2014.

Ljubicic V, ^Burt M, Lunde JA, Jasmin BJ. Resveratrol induces expression of the slow, oxidative phenotype in mdx mouse muscle together with enhanced activity of the SIRT1-PGC-1α axis. Am J Physiol Cell Physiol. 307:C66-82. 2014.

Ljubicic V, ^Burt M, Jasmin BJ. The therapeutic potential of skeletal muscle plasticity in Duchenne muscular dystrophy: phenotypic modifiers as pharmacological targets. FASEB J. 28:548-68, 2014.

Ljubicic V, Jasmin BJ. AMP-activated protein kinase at the nexus of therapeutic skeletal muscle plasticity in Duchenne muscular dystrophy. Trends Mol Med. 19:614-24, 2013.

Ljubicic V, Khogali S, Renaud JM, Jasmin BJ. Chronic AICAR administration attenuates adaptive signaling in dystrophic skeletal muscle. Am J Physiol Cell Physiol. 302:C110-21, 2012.

Ljubicic V, Miura P, ^Burt M, Boudreault L, Khogali S, Lunde JA, Renaud JM, Jasmin BJ. Chronic AMPK activation evokes the slow, oxidative myogenic program in mdx mouse skeletal muscle. Hum Mol Genet. 20:3478-93, 2011.

Lai RY, Ljubicic V, D’souza DD, Hood DA. Effect of chronic contractile activity on mRNA stability in skeletal muscle. Am J Physiol Cell Physiol. 299:C155-63, 2010.

Ljubicic V, Joseph AM, Adhihetty PJ, Huang JH, Saleem A, Uguccioni G, Hood DA. Molecular basis for an attenuated mitochondrial adaptive plasticity in aged skeletal muscle. AGING (Albany NY). 1:818-30, 2009.

Joseph AM, Ljubicic V, Adhihetty PJ, Hood DA. Biogenesis of the mitochondrial Tom40 channel in skeletal muscle from aged animals and its adaptability to chronic contractile activity. Am J Physiol Cell Physiol. 298:C1308-14, 2010.

Huang JH, Joseph AM, Ljubicic V, Iqbal S, Hood DA. Effect of age on the processing and import of matrix-destined mitochondrial proteins in skeletal muscle. J Gerontol A Biol Sci. 65:138-46, 2010.

Ljubicic V, Menzies KJ, Hood DA. Mitochondrial dysfunction is associated with a proapoptotic cellular environment in senescent cardiac muscle. Mech Age Dev. 131:79-88, 2010.

Ljubicic V, Joseph AM, Saleem A, Uguccioni G, Collu-Marchese M, Lai RY, Nguyen L, Hood DA. Transcriptional and post-transcriptional regulation of mitochondrial biogenesis in skeletal muscle: effects of exercise and aging. Biochim Biophys Acta. 1800:223-34, 2010.

Ljubicic V, Hood DA. Specific attenuation of protein kinase activation in muscle with a high mitochondrial content. Am J Physiol Endocrinol Metab. 297:E749-58, 2009.

Ljubicic V, Hood DA. Diminished contraction-induced intracellular signaling towards mitochondrial biogenesis in aged skeletal muscle. Aging Cell. 8:394-404, 2009.

Irrcher I, Ljubicic V, Hood DA. Interactions between ROS and AMP kinase activity in the regulation of PGC-1α transcription in skeletal muscle cells. Am J Physiol Cell Physiol. 296:C116-23, 2009.

Irrcher I, Ljubicic V, Kirwan AF, Hood DA. AMP-activated protein kinase-regulated activation of the PGC-1α promoter in skeletal muscle cells. PLoS One. 3:e3614, 2008.

Ljubicic V, Hood DA. Kinase-specific responsiveness to incremental contractile activity in skeletal muscle with low and high mitochondrial content. Am J Physiol Endocrinol Metab. 295:E195-204, 2008.

Chabi B, Ljubicic V, Menzies KJ, Huang JH, Saleem A, Hood DA. Mitochondrial function and apoptotic susceptibility in aging skeletal muscle. Aging Cell. 7:2-12, 2008.

Yoshida Y, Holloway GP, Ljubicic V, Hatta H, Spriet LL, Hood DA, Bonen A. Negligible direct lactate oxidation in subsarcolemmal and intermyofibrillar mitochondria obtained from red and white rat skeletal muscle. J Physiol. 582:1317-35, 2007.

Adhihetty PJ, Ljubicic V, Hood DA. Effect of chronic contractile activity on SS and IMF mitochondrial apoptotic susceptibility in skeletal muscle. Am J Physiol Endocrinol Metab. 292:E748-55, 2007.

Hood DA, Irrcher I, Ljubicic V, Joseph AM. Coordination of metabolic plasticity in skeletal muscle. J Exp Biol. 209:2265-75, 2006.

Chabi B, Adhihetty PJ, Ljubicic V, Hood DA. How is mitochondrial biogenesis affected in mitochondrial disease? Med Sci Sport Exerc. 37:2102-10, 2005.

Ljubicic V, Adhihetty PJ, Hood, DA. Application of animal models: Chronic electrical stimulation-induced contractile activity. Can J Appl Physiol. 30:625-43, 2005.

Adhihetty PJ, Ljubicic V, Menzies KJ, Hood DA. Differential susceptibility of subsarcolemmal and intermyofibrillar mitochondria to apoptotic stimuli. Am J Physiol Cell Physiol. 289:C994-C1001, 2005.

Ljubicic V, Adhihetty PJ, Hood DA. Role of UCP3 in state 4 respiration during contractile activity–induced mitochondrial biogenesis. J Appl Physiol (1985). 97:976-83, 2004.

Irrcher I, Adhihetty PJ, Joseph AM, Ljubicic V, Hood DA. Regulation of mitochondrial biogenesis in muscle by endurance exercise. Sports Med. 33:783-93, 2003.

Adhihetty PJ, Irrcher I, Joseph AM, Ljubicic V, Hood DA. Plasticity of skeletal muscle mitochondria in response to contractile activity. Exp Physiol. 88:99-107, 2003.

Degree University Year
PostDoc Fellow University of Ottawa 2014
PhD York University 2009
MSc York University 2004
BA York University 2001
Degree Name
MSc Hooriya Masood
Stephanie Mattina
Aislin Osborne
Rozhin Raziee
Erin Webb
PhD Andrew Mikhail
Sean NG
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