Dr. Peter Merrifield
Associate Professor and Associate Scientist, Child Health Research Institute
Ph.D. University of Western Ontario
Office: 428 Medical Sciences Building
Skeletal muscle development, or myogenesis, represents an ideal model system for studying cellular processes such as cell migration, cell signaling, cell cycle regulation and cell differentiation. Understanding myogenesis is extremely important, since myoD -/-, myf5 -/- deficient mice which lack normal muscle development die at birth, and mutant mice lacking muscle specific stem cells (or satellite cells) cannot regenerate muscle in response to injury. The objective of my current research program is to elucidate the cell signaling and epigenetic mechanisms which commit muscle precursor cell to specific myogenic lineages and the role of specific myogenic lineages in the development and regeneration of different muscle fibre types. Specifically, I am using several different rodent models (ex. normal and GFP-expressing nude rats, normal and Pax 7 -/- KO mice) to explore six major themes, including:
1) the epigenetic mechanisms involved with myogenic lineage specification
2) the role of embryonic signaling molecules (such as Shh, Wnts and BMPs) in programming muscle precursor cells into either fast or slow myogenic lineages
3) the ability of over-expression of fibre type specific genes (such as calcineurin, Sox6 and Six1/eyal) to dictate the fibre type of muscle satellite cells
4) the importance of p38 signaling in determining myogenic lineage specification
5) the ability of slow fibres derived from embryonic myoblasts to remodel to fast fibres in response to thyroid hormone and
6) the ability of slow-lineage specified muscle satellite cells, engineered to constitutively express Connexin 43 (Cx43), to become functionally integrated in vivo following direct injection into adult rat myocardium.
The experimental approaches used to pursue these objectives will include cell culture/transduction, cell injection/immunolocalization, immunoprecipitation/western blot analysis, RT/real time PCR and microarray analysis. Discovering the molecular basis for these signaling and epigenetic mechanisms will improve our understanding of how normal and diseased muscle adapt, regenerate and age.
Wisenberg, G., Lekx, K., Zabel, P., Kong, H., Mann, R., Zeman, P., Datta, S., Culshaw, C., Merrifield, P.A., Bureau, Y., Wells, G., Sykes, J. and Prato, F. (2009). Cell Tracking and Therapy Evaluation of Bone Marrow Monocytes and Stromal Cells Using SPECT and CMR in a Canine Model of Myocardial Infection. J. Cardiovasc. Magn. Reson. 11(1): 11-21.
Blackwood, K., Sabondjian, E., Goldhawk, D.E., Kovacs, M., Wisenberg, G., Merrifield, P.A., Prato, F.S., DeMoore, J.M., and Stodilka, R.Z.(2007). "Towards Image Guided Stem Cell Therapy" in Stem Cell Applications in Disease; Nova Publishing, Hauppauge, N.Y.
Jin, Y, Kong, H., Stodilka, R., Wells, R.G., Zabel, P, Merrifield, P.A., Sykes, J. and Prato, F.S. (2005). Determining the minimum number of detectable cardiac-transplanted 111I tropolone-labelled bone-marrow derived mesenchymal stem cells by SPECT. Phys. Med. Biol. 7(50): 4445-4455.
Conway, K., Pin, C., Kiernan, J.A. and Merrifield, P.A. (2004). The E Protein HEB is preferentially expressed in Developing Muscle. Differentiation 72: 327-340.
Pin, C., Hrycyshyn, A., Rogers, K., Rushlow, W. and Merrifield, P.A. (2002). Embryonic and fetal rat myoblasts form different muscle fibre types in an ectopic in vivo environment. Devel. Dynam. 224 (3): 253-266.
Merrifield, P.A. and Atkinson, B.G. (2000). Phylogenetic diversity of myosin expression in muscle. Micro. Res. Tech. 50: 425-429.
Gauthier, F.V., Merrifield, P.A. and Atkinson, G.G. (2000). Postembryonic expression of the myosin heavy chain genes in the limb, tail and heart muscles of metamorphosing amphibian tadpoles. Micro. Res. Tech. 50: 458-472.