Associate Professor of Biological Sciences
PhD, 1998 California Institute of Technology
|Office:||340F Christopher S. Bond Life Sciences Center|
Signaling and activity of skeletal muscle satellite cells
Research descriptionOur group studies development, regeneration and disease in mammalian skeletal muscle, with a focus on extracellular signaling pathways that modify muscle stem cell behavior. These tissue-specific stem cells (satellite cells) are necessary for muscle regeneration, and follow a characteristic pattern of activity in response to local muscle damage. In uninjured muscle they rest in a quiescent, nonproliferative state between the cell membrane of their host muscle fiber and the basal lamina surrounding it. Unlike the majority of adult stem cells, satellite cells do not have a highly organized ‘niche’ to regulate their proliferation and self-renewal. When they sense muscle damage, satellite cells are activated out of quiescence, upregulate muscle-specific genes, and proliferate to form a pool of replacement myoblasts that will eventually differentiate into new muscle cells to repair or replace muscle tissue that has been lost or damaged. Satellite cells that are not directly in the damaged area can be activated as well and recruited to the site to participate in muscle regeneration. The signaling molecules controlling satellite cell activation, proliferation, migration, differentiation, and self-renewal are produced by the muscle fibers, muscle fibroblasts, inflammatory immune cells, and the satellite cells themselves, and are dynamically expressed in space and time. Our ‘big picture question’ is how satellite cells integrate and respond to extracellular signals in order to rapidly, efficiently, and repeatedly respond to muscle damage or disease.
Recently, our research has centered on satellite cell motility and migration. We are working to identify soluble factors released during muscle damage that would promote satellite cell motility and recruitment; matrix-modifying factors that would allow satellite cells to travel through the extracellular matrix; and guidance factors that would direct satellite cell migration pathways and facilitate self-sorting. We study satellite cells from wildtype and disease models of mouse, dog, and human in culture using timelapse microscopy, immunohistochemistry, and gene expression assays, as well as in vivo models of muscle injury and disease in mouse. We also study satellite cell interactions with nonmuscle cells including neurons, glia, macrophages, and interstitial cells. Potential applications of our work are improving cell transplant therapies for conditions such as Duchenne’s muscular dystrophy; our research is funded by the Muscular Dystrophy Association and the National Institutes of Health.
Bentzinger CF#, von Maltzahn J#, Dumont NA, Stark DA, Wang YX, Nhan K, Frenette J, Cornelison DDW and MA Rudnicki (2014). “Wnt7a enhances myogenic stem cell engraftment by promoting motility and self-renewal.” The Journal of Cell Biology 205:97-111
Lund DK, Mouly V, and Cornelison DDW (2014). MMP-14 is necessary but not sufficient for invasion of three-dimensional collagen by human muscle satellite cells” American Journal of Physiology- Cell Physiology 307:140-149
Hettmer S, Li Z, Billin AN, Barr FG, Cornelison DDW, Ehrlich AR, Guttridge DC, Hayes-Jordan A, Helman LJ, Houghton PJ, Khan J, Langenau DM, Linardic CM, Pal R, Partridge TA, Pavlath GK, Rota R, Schäfer BW, Shipley J, Stillman B, Wexler LH, Wagers AJ and C Keller (2014). “Rhabdomyosarcoma: current challenges and their implications for developing therapies” Cold Spring Harb Perspect Med. a025650
Lund DK and DDW Cornelison (2013). “Enter the Matrix: Shape, Signal, and Superhighway.” FEBS J 280: 2089-99
Chowdhury, A.S.; Paul, A.; Bunyak, F.; Cornelison, D.D.W.; Palaniappan, K., "Semi-automated tracking of muscle satellite cells in brightfield microscopy video," Image Processing (ICIP), 2012 19th IEEE International Conference on , vol., no., pp.2825,2828, Sept. 30 2012-Oct. 3 2012 doi: 10.1109/ICIP.2012.6467487
Farina, N. H., Hausburg, M., Betta, N. D., Pulliam, C., Srivastava, D., Cornelison, D. D. W., & Olwin, B. B. (2012). A role for RNA post-transcriptional regulation in satellite cell activation. Skeletal Muscle 2:21
Stark, D. A., Karvas, R. M., Siege, A. L., & Cornelison, D. D. W. (2011). Eph/ephrin interactions modulate muscle satellite cell motility and patterning. Development, 138(24), 5279-5289.
Alfaro, L. A. S., Dick, S. A., Siegel, A. L., Anonuevo, A. S., McNagny, K. M., Megeney, L. A., Cornelison D. D. W., Rossi, F. M. V. (2011). CD34 promotes satellite cell motility and entry into proliferation to facilitate efficient skeletal muscle regeneration. Stem Cells, 29(12), 2030-2041.
Berg, Z., Beffa, L. R., Cook, D. P., & Cornelison, D. D. W. (2011). Muscle satellite cells from GRMD dystrophic dogs are not phenotypically distinguishable from wild type satellite cells in ex vivo culture. Neuromuscular Disorders, 21(4), 282-290.
Siegel, A. L., Kuhlmann, P. K., & Cornelison, D. D. W. (2011). Muscle satellite cell proliferation and association: New insights from myofiber time-lapse imaging. Skeletal Muscle, 1:7
Pisconti, A., Cornelison, D. D. W., Olguín, H. C., Antwine, T. L., & Olwin, B. B. (2010). Syndecan-3 and notch cooperate in regulating adult myogenesis. Journal of Cell Biology, 190(3), 427-441
Honors & Awards
Selected honors and awards
College of Arts and Sciences Purple Chalk Award for Excellence in Teaching 2011