Dr. Graham Holloway
Office: ANNU 330B
Lab: ANNU 322
As a highly competitive athlete I have always been interested in understanding skeletal muscle physiology. In my Undergraduate degree at McMaster University this was more of idle curiosity, rather than a career path. However, when I was introduced to the research process and a larger understanding of skeletal muscle physiology during my masters training at the University of Waterloo, I immediately found a career I was interested in pursing. My interest in understanding how muscle utilizes substrates (carbohydrates and fats) during exercise was further strengthened during my PhD at the University of Guelph, as I became aware of the ability to apply general physiology to the study of various diseases. My research during my post-doctoral training, which has continued during my faculty position, has been focused on using exercise as a model to study novel regulation in fuel selection, and apply this knowledge to the study of type 2 diabetes, a condition believed to be caused or exacerbated by a decrease in the ability of muscle to use fat as a fuel source.
Hon B.Kin. - McMaster University
M.Sc. - University of Waterloo
Ph.D. - University of Guelph
My research has been focused on understanding the regulation of mitochondrial fatty acid oxidation (breakdown of fat yielding energy) in skeletal and cardiac muscle, which can be influenced by 1) the transport of fat into mitochondria and 2) mitochondrial content. I use a variety of techniques to examine mitochondrial function (isolated mitochondria, permeabilized fibres, whole muscle incubations), use molecular biological approaches to up-and down-regulate mitochondrial proteins, as well exercise and aerobic training to study what regulates mitochondrial fatty acid oxidation. We apply this knowledge to the study human exercise performance as well as type 2 diabetes, a condition that has been speculated to have alterations in mitochondria as a key event in the progression and/or development of this disease.
Lally JSV, Herbst EAF, Matravadia S, Maher AC, Perry CGR, Ventura-Clapier R, Holloway GP: Over-expressing Mitofusin-2 in Health Mature Mammalian Skeletal Muscle Does not Alter Mitochondrial Bioenergetics. Plos One 8(1), 2013.
Smith BK, Perry CGR, Koves TR, WRight DC, Smith JC, Neufer PD, Muoio DM, Holloway GP: Identification of a novel malonyl-CoA IC(50) for CPTI: implications for predicting in vivo fatty acid oxidation rates. Biochem J 448: 13-20, 2012
Perry, CG, Kane DA, Herbst EA, Mukai K, Lark DS, Wright DC, Heigenhauser GJ, Neufer PD, Spriet LL, Holloway GP: Mitochondrial creatine kinase activity and phosphate shuttling are acutely regulated by exercise in human skeletal muscle. J Physiol 590:5475-86, 2012.
Lally JS, Snook LA, Han XX, Chabowski A, Bonen A, Holloway GP: Subcellular lipid droplet distribution in red and white muscles in the obese Zucker rat. Diabetologia 55(2):479-88, 2012
Smith BK, Jain SS, Rimbaud S, Dam A, Quadrilatero J, Ventura-Clapier R, Bonen A, Holloway GO: FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation. Biochem J 437(1):125-34, 2011.
Holloway GP , Jain SS, Bezaire V, Han XX, Glatz JF, Luiken JJ, Harper ME and Bonen A: FAT/CD36 null mice reveal that mitochondrial FAT/CD36 is required to up-regulate mitochondrial fatty acid oxidation in contracting muscle. Am J Physiol, Reg. Integ. Comp. Physiol. in press 2009
Holloway GP, Benton CR, Mullen KL, Yoshida Y, Snook LA , Han XX, Glatz JFC, Luiken JJ, Lally J, Dyck DJ and Bonen A. In obese rat muscle transport of palmitate is increased and is channeled to triacylglycerol storage despite an increase in mitochondrial palmitate oxidation Am J Physiol, Endo. and Metab 296: E738-47, 2009
Holloway GP, Bonen A, Spriet LL. Regulation of skeletal muscle mitochondrial fat metabolism in lean and obese individuals. American Journal of Clinical Nutrition 89: 455S-62, 2009
Holloway GP, Perry CG, Thrush AB, Heigenhauser GJ, Dyck DJ, Bonen A, Spriet LL: PGC-1alpha's relationship with skeletal muscle palmitate oxidation is not present with obesity despite maintained PGC-1alpha and PGC-1beta protein. Am J Physiol, Endo. and Metab 294:E1060-1069, 2008
Holloway GP , Lally J, Nickerson JG, Alkhateeb H, Snook LA, Heigenhauser GJ, Calles-Escandon J, Glatz JF, Luiken JJ, Spriet LL, Bonen A: Fatty acid binding protein facilitates sarcolemmal fatty acid transport but not mitochondrial oxidation in rat and human skeletal muscle. J Physiol 582:393-405, 2007
Grad Students and Post-Doctoral Fellows