Associate Professor, Department of Human Anatomy and Cell Science
Scientist, Children’s Hospital Research Institute of Manitoba
The basis of my research is to investigate the regulation of the myocardin family of transcription coactivators, and the two downstream related transcription factors, myocyte enhancer factor-2 (MEF2), and serum response factor (SRF), that are activated by the myocardins.
Both MEF2 and SRF are enriched in muscle tissue, and genetic deletion of these transcription factors causes severe developmental abnormalities of the musculoskeletal and cardiovascular systems; as well as, a resistance to certain cardiac disorders. MEF2 and SRF also play a critical role in post-natal remodelling of skeletal, cardiac, and vascular smooth muscle.
In skeletal muscle MEF2 responds to multiple calcium-mediated signals to promote an oxidative phenotype and improves muscle insulin sensitivity; whereas in cardiac muscle, MEF2 and SRF play critical roles in physiological cardiac hypertrophy in response to exercise training, and pathological remodelling of the heart during the progression to heart failure.
Finally, in vascular smooth muscle, MEF2 and SRF modulate the cellular phenotype between contractile and proliferation, a process that underlies vascular diseases, such as atherosclerosis and restenosis following angioplasty.
561 John Buhler Research Center