In many tissues, wound healing and regeneration depends on stem cells to replace the lost or damaged cells. In injured skeletal muscle, a dedicated muscle stem cell population gives rise to new muscle myofibers after an acute injury. In chronic diseases, however, muscle regeneration fails and healthy muscle is gradually replaced with fibrotic scar and fat tissue, a process called fatty fibrosis. This fatty fibrosis of muscle is a prominent feature of chronic muscle diseases such as Duchenne muscular dystrophy (DMD), sarcopenia (age-related loss of skeletal muscle and strength), obesity and diabetes. There are no cures for DMD and no specific therapies for either DMD or sarcopenia.
Coordinating cell-cell interactions is critical for regenerating complex tissues after injury or disease. Primary cilia are small, immotile, microtubule-based cell projections and have evolved to receive and interpret extracellular cues. Cilia play a crucial role in intercellular communication during development and defects in cilia lead to embryonic lethality in both mice and humans. While cilia are present on the majority of cells in our body, there’s little known about how they function or participate in the repair of adult tissues.
It was recently discovered that cilia coordinate muscle repair by controlling the communication between the muscle stem cell population and its support cells. The Kopinke Lab is now building on this work by investigating how ciliary signaling coordinates cellular communication between stem cells and their niche, to understand how cilia-based communication goes awry in disease and to identify novel pharmacological tools to combat cilia-associated diseases such as fatty fibrosis.
- Hilgendorf, K.I., Johnson, C.T., Mezger, A., Rice, S.L., Norris, A.M., Demeter, J., Greenleaf, W.J., Reiter, J.F., Kopinke, D*., Jackson, P.K., 2019. Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis. Cell 179, 1289-1305 e1221. *co-corresponding author
- Wang, M., Law, M.E., Davis, B.J., Yaaghubi, E., Ghilardi, A.F., Ferreira, R.B., Chiang, C.-W., Guryanova, O.A., Kopinke, D., Heldermon, C.D., Castellano, R.K., Law, B.K., 2019. Mechanistic Elucidation of the Antitumor Properties of a Novel Death Receptor 5 Activator. Cell Death Discovery, doi/10.1101/700906. Accepted.
- Kopinke D, Roberson EC, Reiter JF. Ciliary Hedgehog Signaling Restricts Injury-Induced Adipogenesis. Cell. 2017;170(2):340-51 e12. doi: 10.1016/j.cell.2017.06.035.
- Veniaminova NA, Vagnozzi AN, Kopinke D, Do TT, Murtaugh LC, Maillard I, Dlugosz AA, Reiter JF, Wong SY. Keratin 79 identifies a novel population of migratory epithelial cells that initiates hair canal morphogenesis and regeneration. Development. 2013;140(24):4870-80. doi: 10.1242/dev.101725.
- Kopinke D, Brailsford M, Pan FC, Magnuson MA, Wright CV, Murtaugh LC. Ongoing Notch signaling maintains phenotypic fidelity in the adult exocrine pancreas. Dev Biol. 2012;362(1):57-64. doi: 10.1016/j.ydbio.2011.11.010.
- Kopinke D, Brailsford M, Shea JE, Leavitt R, Scaife CL, Murtaugh LC. Lineage tracing reveals the dynamic contribution of Hes1+ cells to the developing and adult pancreas. Development. 2011;138(3):431-41. doi: 10.1242/dev.053843.
- Wang X, Kopinke D, Lin J, McPherson AD, Duncan RN, Otsuna H, Moro E, Hoshijima K, Grunwald DJ, Argenton F, Chien CB, Murtaugh LC, Dorsky RI. Wnt signaling regulates postembryonic hypothalamic progenitor differentiation. Dev Cell. 2012;23(3):624-36. doi: 10.1016/j.devcel.2012.07.012.
- Kopinke D, Murtaugh LC. Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreas. BMC Dev Biol. 2010;10:38. doi: 10.1186/1471-213X-10-38.