Amelia E. Hufford, 2013 Wagner Prize Recipient

Amelia E. Hufford
Ph.D. in Microbiology,  May 2013
Ravichandran Lab

“Phosphatidylserine recognition receptors: promoters of muscle development and apoptotic cell engulfment”

In the laboratory of Dr. Kodi Ravichandran, Amelia’s thesis research focused on understanding the role of the phosphatidylserine (PtdSer) receptor, BAI1, and apoptotic cells in muscle development and repair. Myoblasts are muscle progenitor cells that must fuse with one another during muscle development to form multinuclear myofibers. Amelia demonstrated that BAI1 expression in myoblasts positively regulates myoblast fusion, which is dependent on the activation of the ELMO/Dock180/Rac signaling pathway. In vivo, myofibers from Bai1-/- mice are smaller than wild-type littermates, and muscle regeneration after injury was also impaired in Bai1-/- mice, highlighting a role for BAI1 in mammalian myogenesis. Amelia further observed that during myoblast fusion, a fraction of myoblasts undergo apoptosis and expose PtdSer, an established ligand for BAI1. Moreover, she determined that blocking apoptosis potently impairs fusion, and adding back apoptotic myoblasts restores fusion. Finally, primary human myoblasts could be induced to form myotubes by adding apoptotic myoblasts, even under normal growth conditions. Together, these findings identify BAI1 and apoptotic cells as novel promoters of myoblast fusion, with significant implications for muscle development and repair.