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My laboratory is interested in understanding the molecular mechanisms of muscle development with the long-term view of using stem cells to replace damaged muscle. Embryonic stem cells or embryonal carcinoma cells can be induced to differentiate into cardiac and skeletal muscle. However, this process is not very efficient and only a minority of the cells differentiates down a given developmental pathway. In order to enhance the extent of differentiation into muscle, it is essential to identify the network of transcription factors that specify different types of muscle and to understand how signaling pathways control the expression and function of the individual transcription factors in the network. A solid grasp of the fundamental mechanisms involved in muscle development will be essential in designing future therapies based on adult or embryonic stem cells for restoring cardiac sufficiency or replacing muscle in patients with muscle atrophy.
Canadian Institutes of Health Research Operating Grants:
- The molecular biology of muscle development
- The molecular basis of cardiac muscle development
- US Muscular Dystrophy Association
- Molecular approaches to enhance myogenesis in human embryonic stem cells
- Al Madhoun AS, Voronova A, Ryan T, Zakariyah A, McIntire C, Gibson L, Shelton M, Ruel M, Skerjanc IS. Testosterone enhances cardiomyogenesis in stem cells and recruits the androgen receptor to the MEF2C and HCN4 genes. J Mol Cell Cardiol. 2013 Jul;60:164-71. doi: 10.1016/j.yjmcc.2013.04.003. Epub 2013 Apr 15.
- D. Kuraitis, D. Ebadi, P. Zhang, E. Rizzuto, B. Vulesevic, D.T. Padavan, A. Al Madhoun, K.A. McEwan, T. Sofrenovic, K. Nicholson, S.C. Whitman, T.G. Mesana, I.S. Skerjanc, A. Musarò, M. Ruel, and E.J. Suuronen, Injected matrix stimulates myogenesis and regeneration of mouse skeletal muscle after ischemic injury, European Cells and Materials, 24:175 (2012).
- Voronova, A., Al Madhoun, A., Fischer, A., Shelton, M., Karamboulas, C., and Skerjanc, I.S.* Gli2 and MEF2C activate each other’s expression and function synergistically during cardiomyogenesis in vitro. Nucleic Acids Research, 40(8):3329-3347 (2012).
- Kennedy, K.A.M., Sandiford, S.D.E., Skerjanc, I.S., and Li, S. S-C. Reactive oxygen species and the neuronal fate. Cell. Mol. Life Sci. Jan;69(2):215-21 (2012).
- Dawson, J., Schussler, O., Al Madhoun, A., Menard, C., Ruel, M., and Skerjanc, I.S.* Collagen (+RGD and –RGD) scaffolds support cardiomyogenesis after aggregation of mouse embryonic stem cells. In Vitro Cell Dev Biol Anim. Oct;47(9):653-64 (2011).
- Ryan T, Liu J, Chu A, Wang L, Blais A, Skerjanc IS*, Retinoic Acid Enhances Skeletal Myogenesis in Human Embryonic Stem Cells by Expanding the Premyogenic Progenitor Population, Stem Cell Rev, 2011 Jul 7. [Epub ahead of print]
- Ashraf Said Al-Madhoun, Virja Mehta, Grace Li, Daniel Figeys, Nadine Wiper-Bergeron, and Ilona S. Skerjanc*, Skeletal myosin light chain kinase regulates skeletal myogenesis by phosphorylation of MEF2C, EMBO J., May 10;30(12):2477-89 (2011).
- Anastassia Voronova, Anna Fischer, Tammy Porter, Ashraf Al Madhoun, and Ilona S. Skerjanc*. Ascl1/Mash1 is a novel target of Gli2 during Gli2-induced neurogenesis in P19 EC cells, Plos One, Apr 29;6(4):e19174 (2011).
- Avdic V, Zhang P, Lanouette S, Voronova A, Skerjanc I, Couture JF*. Fine-tuning the stimulation of MLL1 methyltransferase activity by a histone H3-based peptide mimetic. FASEB J. 25 (3):960-7 (2011).
- Gianakopoulos PJ, Mehta V, Voronova A, Cao Y, Yao Z, Coutu J, Wang X, Waddington ML, Tapscott SJ, Skerjanc IS*. MyoD directly upregulates premyogenic mesoderm factors during induction of skeletal myogenesis in stem cells. J Biol Chem. Jan 28;286(4):2517-25 (2011).
- Kennedy, K.A.M, Ostrakhovitch, E.A., Sandiford, S.D.E., Dayarathna, T, Xie. X., Waese, E.Y.L., Chang,W.Y., Feng, Q., Skerjanc, I.S., Stanford, W.L. and Li, S.S.C. *, Mammalian Numb Interacting Protein1/Dual Oxidase Maturation Factor1 directs neuronal fate in stem cells, J Biol Chem, June 4; 285(23):17974-85 (2010).
- Savage, J., Voronova, A., Mehta, V., Sendi-Mukasa, F., and Skerjanc, I.S.*, Canonical Wnt signaling regulates Foxc1/2 expression in P19 cells, Differentiation, Jan;79(1):31-40 (2010).
- Dawson, J.E., Boisvenue, S., Skerjanc, I.S.* 1, and Griffith, M.1, A P19 cardiac cell line as a model for evaluating cardiac tissue engineering biomaterials, Open Tissue Engineering and Regenerative Medicine Journal, 2: 53-62 (2009).1Authors contributed equally. Read article (1.24 MB)
- Kennedy, K.A.M., Porter, T. , Mehta, V., Price, F. , Ryan, S., Karamboulas, C., Savage, J., Drysdale, T., Bennett, S. and Skerjanc, I.S.*, Bone Morphogenetic Protein 4 and Retinoic Acid function antagonistically in regulating cardiac and skeletal muscle development, BMC Biol. Oct 8;7(1):67 (2009).
- Gianakopoulos, P. and Skerjanc, I.S.*, Cross-talk between Hedgehog and Bone Morphogenetic Proteins occurs during Cardiomyogenesis in P19 cells, In Vitro Cellular & Developmental Biology – Animal, 2009 Oct;45(9):566-72 (338 KB). :566-72 (2009). .
- Savage, J., Conley, A.J., Blais, A. and Skerjanc, I.S.*, Sox15 regulates pre-skeletal mesoderm formation in P19 cells, Stem Cells, 27(6):1231-43 (1.37 MB) (2009).
- Abu-Farha, M, Lambert, J.P., Al-Madhoun, A.S., Elisma, F., Skerjanc, I.S., and Figeys, D., A combined proteomic and genomic approach to characterize SMYD2, a histone lysine methyltransferase, Canadian-Society of Biochemistry Molecular and Cellular-Biology, Biochemistry and Cell Biology, 87(1) 369-370A (2009).
- Mitchell L, Lambert JP, Gerdes M, Al-Madhoun AS, Skerjanc IS, Figeys D, Baetz K.* Functional dissection of the NuA4 histone acetyltransferase reveals its role as a genetic hub and that Eaf1 is essential for complex integrity, Mol Cell Biol. 28 (7):2244-56 (715 KB) (2008).
- Abu-Farha M, Lambert JP, Al-Madhoun AS, Elisma F, Skerjanc IS, Figeys D.* The tale of two domains: Proteomic and genomic analysis of SMYD2, a new histone methyltransferase. Mol Cell Proteomics, 7(3):560-72 (589 KB) (2008).