McMaster University

McMaster University

Mark Tarnopolsky

Dr. Mark Tarnopolsky

Professor,

Department of Pediatrics
Deparment of Medicine

Ph: 905-521-2100 x 75226
Fx: 905-577-8380
Em: tarnopol@mcmaster.ca


Research Theme

Neuromuscular and neurometabolic diseases and rehabilitation

  • Primary Research: Mitochondrial disease/dysfunction
  • Secondary Research: Muscle disease

Key words

Mitochondrial disease, aging, muscle metabolism, exercise adaptation, mitochondrail function

Research Program Overview

Main Research Areas:

  • The overall goal of my research program is to discover and evaluate therapies that will enhance muscle function in people with acquired and genetic neuromuscular diseases and mitochondrial dysfunction. We have a particular interest in the potential for exercise, pharmacological and nutraceutical interventions to enhance muscle function and improve muscle mass. Our program spans the research disciplines from cell culture all the way to small-scale clinical trials. We have been successful at very rapidly turning basic biological principles into proof of concept studies and completing small-scale clinical trials in patients with muscle and mitochondrial dysfunction. The main underlying theme of much of my research is related to mitochondrial dysfunction and genetic diseases affecting the mitochondria, but also towards conditions associated with mitochondrial dysfunction including aging, immoblization, type 2 diabetes and obesity. Our program consists of a large staff with three research assistants, and animal technician, two laboratory technicians, eight PhD students, one to two postdoctoral fellows and a host of 4th year and summer students. We have a large number of clinical and basic science collaborators both at McMaster University, nationally and internationally and collaborate openly to advance science in this area towards the ultimate goal of improving function in the patients with neuromuscular and mitochondrial disorder.
  • We are currently involved in randomized clinical trial looking at the effective Deferiprone in patients with Friedreich’s ataxia.  We are also finalizing the details for a randomized double blind trial looking at triacetyluridine in the treatment of mitochondrial cytopathies and hope to start this later in 2009. 


Current Projects

  • Polymerase gamma mutator mouse as a model of aging in mitochondrial disease – this mouse has a knock in mutation in the polymerase gamma gene resulting in defective proofreading of mitochondrial DNA transcription. This leads to mitochondrial dysffunction and premature agin. We have shown that exercise prevents many of the negative phenotypic affects on these animals including brain atrophy, cardiac hypertrophy and muscle atrophy and we are working out the biochemical and molecular mechanisms of this protective effect.
  • Mitochondrial involvement in immobilization induced muscle atrophy – we have mapped out the transcriptome expression pattern early (48 hours) and later (14 days) in the immobilization process by unilaterally applying a leg brace to healthy volunteers.  We have shown that the activation of proteolytic pathways is minimal; however, the down-regulation of mitochondrial function and other energy driving pathways is quite robust and coordinate.  We are now looking at various countermeasures including exercise and nutraceutical interventions to try and mitigate against immobilization induced muscle atrophy.
  • Evaluation of creatine monohydrate as a therapeutic compound – we have shown that patients with neuromuscular and mitochondrial diseases have low levels of creatine in their muscle and have found beneficial affects in muscular dystrophy and in primary mitochondrial cytopathies.  We have mapped out the transcriptome expression profile and found a number of interesting pathways which may help to explain some of the neuroprotective benefits seen with creatine supplementation in a variety of animal models of neurological disease. 

Publications & Achievements

In 2008 we published over 30 peer reviewed papers and started the clinical trial evaluating Deferiprone in Friedreich’s ataxia.  The research program is continuing to produce exciting results in the area of mitochondrial dysfunction, aging, limb immobilization through funding from private donors, CIHR, NSERC and CHRP.

  • Crane JD, Ogborn DI, Cupido C, Melov S, Hubbard A, Bourgeois JM and Tarnopolsky MA. Massage Therapy Attenuates Inflammatory Signaling After Exercise-Induced Muscle Damage. Sci Transl Med 4, 119ra13 (2012)
  • Tarnopolsky M, Mahoney D, Vajsar J, Rodriguez C, Doherty T, Roy B, Biggar D.  Creatine monohydrate enhances strength and body composition in boys with duchenne muscular dystrophy.  Neurology, 62(10): 1771- 1777, 2004. (US-MDA
  • Melov S, Tarnopolsky MA, Beckman K, Felkey K, Hubbard A.  Resistance exercise reverses aging in human skeletal muscle.  PloS ONE, 2(5):E465, 2007.
  • Tarnopolsky M, Zimmer A, Paikin J, Safdar A, Aboud A, Pearce E, Roy B, Doherty.  Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults.  PloS ONE, 2(10): E991, 2007.
  • Devries M, Lowther S, Glover A, Hamadeh M, Tarnopolsky M.  IMCL Area Density, but not IMCL Utilization, are Higher in Women During Moderate Intensity Endurance Exercise as Compared with Men.  Am J Physiol Regul Integr Comp Physiol. 293(6):R2336-42, 2007.
  • Safdar A, Yardley N, Snow R, Melov S, Tarnopolsky M.  Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation.  Physiol. Genomics, 32(2):219-228, 2087.

Secondary Contact

Delores Reid
Phone: 905-521-2100 x75226
Email: reidd@hhsc.ca
Title: Administrative Assistant

Research Staff

Alissa Aboud and Erin Pearce - Research Assistants
Arkan Al-Abadi and Elise Glover - Postdoctoral Fellows
Mahmood Akhtar – Chief Laboratory Technician
Suzanne Southward – Laboratory Technician
Bart Hettinga – Animal Study Technician


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