Assistant Professor, Department of Cellular and Molecular Medicine, Senior Scientist Ottawa Hospital Research Institute
Work: (613) 737-8899 ext. 70339
In the Dilworth Lab, our research is focused on how muscle stem cells work to regenerate muscle tissue and how the environment they live in can influence their ability to repair muscle damage. This capacity to regenerate is necessary to replace, grow and repair our skeletal muscle throughout our lives. When something goes wrong with the function of these stem cells (called satellite cells), muscle tissue wastes away, which is the case for people suffering from muscular dystrophies. And as we age, maintaining muscle mass becomes increasingly difficult, also a result of changes in the effectiveness of our satellite cells. We are trying to address both of these areas by exploring how these stem cells respond to epigenetic influences, and how we can modify the muscle environment in which these satellite cells live to improve their regenerative function.
The idea behind epigenetics is that the hardwired DNA blueprint in our cells can be influenced by the environment to shape our body's destiny. Indeed, how our muscles are used (active versus sedentary) and nourished will make a difference in how our DNA blueprint is utilized within the stem cells. We are particularly interested in how epigenetic influences can change the way our DNA is packaged within the cell, a process that greatly controls access to specific genes within our hardwired genetic code. Different cells in the body need access to different parts of our DNA. This DNA access is critical for cells to be healthy and work properly as it allows the proper genes for a specific cell type to be turned on.
We are continually expanding our understanding of the genes necessary to maintain muscle stem cells in a healthy, functional state. The goal of the Dilworth Lab is to understand why the genes that maintain stem cells in a healthy state sometimes get turned off and how we can use epigenetics to turn these genes back on, so our satellite cells can function properly and effectively throughout our lifetime.
M. Brand, K. Nakka, J. Zhu, and F.J. Dilworth. Polycomb/Trithorax Antagonism: Cellular Memory in Stem Cell Fate and Function. Cell Stem Cell 4: 518-533, 2019.
H. Faralli, C. Wang, A. Benyoucef, S. Sebastian, L. Zhuang, A. Chu, C. Palii, C. Liu, B. Camellato, M. Brand, K. Ge, and F.J. Dilworth. H3K27-demethylase activity of UTX/KDM6A is essential for skeletal muscle regeneration. Journal of Clinical Investigation 126: 1555-1565, 2016.
K. Singh, M. Cassano, E. Planet, S.Sebastian, S.M. Jang, G. Sohi, J. Choi, H.D. Youn, F.J. Dilworth*, and D. Trono*. KAP1 functions as a phosphorylation-inducible activator of MyoD function during skeletal muscle differentiation. Genes & Dev 29: 513-525, 2015. *Co-corresponding authors
S. Sebastian, H. Faralli, Z. Yao, P. Rakopoulos, C. Palii, Y. Cao, K. Singh, Q-C. Liu, A. Chu, A. Aziz, M. Brand, S.J. Tapscott, and F.J. Dilworth. Tissue-specific splicing of a ubiquitously expressed transcription factor is essential for muscle differentiation. Genes & Dev 27: 1247-1259, 2013.
Q-C. Liu, X. Zha, H. Faralli, H. Yin, C. Louis-Jeune, E. Perdiguero, E. Pranckeviciene, P. Munoz-Canoves, M. Rudnicki, M. Brand, C. Perez-Iratxeta, and F.J. Dilworth. Comparative expression profiling identifies differential roles for Myogenin and p38a MAPK signaling in myogenesis. J Mol Cell Biol. 4 : 386-397, 2012.
S. Seenundun, S. Rampalli, Q-C. Liu, A. Aziz, C. Palii, S.H. Hong, A. Blais, M. Brand, K. Ge, F.J. Dilworth. UTX-mediated demethylation of H3K27me3 at muscle-specific genes during myogenesis. EMBO Journal 29: 1401-1411, 2010.
S. Rampalli, L. Li, E. Mak, K. Ge, M. Brand, S.J. Tapscott, and F.J. Dilworth. p38 MAPK signaling pathway regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation. Nature Struct Mol Biol 14: 1150-1156, 2007.