Assistant Professor, Meinig School of Biomedical Engineering
Muscle stem cells (also called satellite cells) reside in defined microenvironmental compartments in skeletal muscle tissue and are essential for its homeostasis and regeneration throughout adulthood. After muscle damage, muscle stem cells (MuSCs) divide through self-renewal, yielding progeny that both retain a Pax7-expressing stem-cell phenotype and also differentiate into myogenic progenitor cells (myoblasts), which further commit and fuse to repair myofibers. In aging and inherited muscular dystrophies, MuSC contributions to muscle repair are defective, owning to an altered regulation of self-renewal fate outcomes resulting in aberrant differentiation and premature senescence. We have recently identified that aging-related MuSC dysfunction is due in part to a heterogeneous and cell-autonomous activation of the p38 MAPK pathway and devised an ex vivo strategy, based on mechano-sensitive signaling, to rejuvenate aged MuSCs. In this talk, I will discuss recent and on-going efforts to dissect the MuSC cell-fate regulatory networks using systems-level gene expression and phosphoprotein network models. We have employed single-cell mass cytometry and RNA-sequencing to provide a refined set of molecular definitions to the muscle stem and progenitor cell functional hierarchy and discovered dysfunctional MuSC subpopulations that are increasing observed in advanced aging. Based on these insights, we have designed combinatorial biomaterial-based microenvironments to engineer the selective expansion of transplantable MuSCs, and have resolved biomanufacturing approaches for autologous muscle cell therapies at the clinical scale.
Benjamin D. Cosgrove is an Assistant Professor in the Meinig School of Biomedical Engineering at Cornell University in Ithaca, NY, where he directs the Laboratory of Regenerative Systems Biology. His research group develops and implements systems biology and biomaterials engineering approaches to study how cell–cell communication and signal transduction networks regulate stem and progenitor cell function in skeletal muscle regeneration, and how these processes become dysfunctional in aging and muscular dystrophies. Dr. Cosgrove earned a Bachelor’s in Biomedical Engineering at the University of Minnesota, a Ph.D. in Bioengineering at the Massachusetts Institute of Technology under the supervision of Dr. Douglas Lauffenburger and Dr. Linda Griffith, and completed a postdoctoral fellowship at the Stanford University School of Medicine with Dr. Helen Blau. His research has been supported by a Whitaker Foundation Graduate Research Fellowship, a Stanford Molecular Imaging Scholars Fellowship, and NIH K99/R00 Pathway-to-Independence Award. He has been recognized by a Biomedical Engineering Society (BMES) Graduate Research Award (2008), a Rising Star Award from the Cellular and Molecular Bioengineering Special Interest Group of BMES (2015), and a Young Innovator of Cellular and Molecular Bioengineering Award (2017).