John Charles McDermott
Full Professor, Department of Biology
Lay Research Summary
Dr. McDermott’s lab specifically focuses on the mechanisms that cause a simple cell to become more specialized. This work is primarily undertaken using cardiac, skeletal and smooth muscle cells and neurons as model systems and is aimed at understanding the role of specialized proteins which bi ...read morend to DNA in orchestrating gene expression which is specific to particular types of tissue. Research interested concern the basic regulatory mechanisms involved in muscle cellular differentiation. This work is primarily undertaken using muscle cells as a model system and is aimed at understanding the role of transcription factors in orchestrating muscle-specific differentiation. read less
Scientific Research Summary
Dr. McDermott’s interests lie with the orchestration of transcription during development of striated muscle. These studies involve a proteome level analysis of transcriptional regulatory proteins to determine how signal transduction pathways control their activity. The genesis of this work was ...read more in identifying DNA binding proteins that are involved in transcriptional regulation during muscle development. Subsequent work explored the mechanisms by which these factors regulate cellular gene expression and differentiation. A main focus of our work has been the molecular cloning and characterization of a family of transcription factors (four genes, labeled MEF2A-D) that regulate the expression of many cardiac, smooth and skeletal muscle specific genes via the myocyte enhancer factor 2 (MEF2) cis- element. Based on their structural similarity, these genes belong to the MADS superfamily of DNA binding proteins that are involved in cell fate specification in many organisms ranging from yeasts to humans. Since the identification of the MEF2 gene family, further studies have been undertaken to assess the biological role of these genes during cardiac and skeletal muscle differentiation as well as in a variety of post-natal contexts such as cardiac hypertrophy and muscle regeneration. It is well known that various intracellular signaling pathways potently regulate cell differentiation by targeting nuclear transcription factors. Moreover, muscle differentiation is extremely sensitive to the action of various growth factors. Therefore, our aim is to delineate the growth factor-activated signaling pathways that specifically converge on and modulate key transcriptional regulators such as MEF2 proteins during myogenesis. We are currently dissecting the effects of kinase mediated phosphorylation of MEF2 protein in order to fully understand how it serves as a nuclear sensor of growth factor -activated signaling pathways. In this regard we have reported a key role of the p38 MAP kinase pathway in targeting MEF2 in the somites during embryogenesis. Included in this post translational analysis of MEF2 function is the identification of MEF2 interacting proteins using state of the art tools in Mass Spectrometry. Studies are also ongoing to determine the contribution of other transcriptional regulators such as the Fra2 subunit of the AP-1 complex and the Smad7 protein to the myogenic program in cardiac and skeletal muscle cells. This work is supported by the Canadian Institutes for Health Research (CIHR), the Natural Sciences and Engineering Research Council (NSERC) of Canada and the Heart and Stroke Foundation of Canada (HSF). read less
Cross-talk between glycogen synthase kinase 3β (GSK3β) and p38MAPK regulates myocyte enhancer factor 2 (MEF2) activity in skeletal and cardiac muscle.
Journal: J Mol Cell Cardiol.
Suppression of a MEF2-KLF6 Survival Pathway by PKA Signaling Promotes Apoptosis in Embryonic Hippocampal Neurons.
High-Resolution Protein Interaction Map of the Drosophila melanogaster p38 Mitogen-Activated Protein Kinases Reveals Limited Functional Redundancy.
Journal: Mol Cell Biol.
A novel RhoA/ROCK- CPI-17 -MEF2C signaling pathway regulates vascular smooth muscle cell gene expression.
Journal: J Biol Chem.
A method for the direct identification of differentiating muscle cells by a fluorescent mitochondrial dye.
Journal: PLoS One.
Honours & Awards
The Canadian Institutes of Health Research (CIHR) Grant
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