Among gene mutations that cause axonal forms of Charcot-Marie-Tooth disease are multiple aminoacyl-tRNA synthetase genes. We are investigating mechanisms by which these mutations cause axonal dysfunction, combining molecular dynamic modeling of effects of mutations on enzyme structure with functional studies of motor and sensory neurons differentiated from human induced pluripotent stem cells bearing CMT-associated mutations.
- Investigators: Alec Smith, Mark Bothwell, Matt Childers