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.

K. Nakka, S. Hachmer, Z. Mokhtari, R. Kovac, H. Bandukwala, C. Bernard, Y. Li, G. Xie, C. Liu, M. Fahalli, L. Megeney, J. Gondin, B. Chazaud, M. Brand, X. Zha, K. Ge, and F.J. Dilworth. JMJD3 activated hyaluronan synthesis drives muscle regeneration in an inflammatory environment. Science 377: 666-669, 2022.

D. Robinson, M. Ritso, G. Nelson, Z. Mokhtari, K. Nakka, H. Bandukwala, S. Goldman, P. Park, R. Mounier, B. Chazaud, M. Brand, M. Rudnicki, K. Adelman, F.J. Dilworth. Negative elongation factor regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation. Dev Cell 56: 1014-1029, 2021.

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.

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.

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.