The overall goal of my laboratory is to understand the molecular mechanisms of neuromuscular diseases using in vitro and animal modeling, based on insights from human genetics, to develop novel therapeutic agents. We are particularly interested in inherited neuropathy (Charcot-Marie-Tooth disease), and amyotrophic lateral sclerosis (ALS). The molecular pathways defined by genes mutated in hereditary neuromuscular diseases provide insight into molecular pathogenesis, and are potential candidates for therapeutic manipulation. To investigate mechanisms of motor neuron disease/ALS we are exploring the role of mutations in both the repeat expansion in the C9orf72 gene, and point mutations in the TARDBP gene, using human induced pluripotent stem cell (iPSC)-derived motor neurons and mouse models. To investigate Charcot-Marie-Tooth disease we are studying (i) the mechanism of mutations in the Mitofusin 2 gene in axonal CMT, and (ii) the use of iPSC-derived Schwann cells from patients with CMT type 1A (the most common genetic form) to both model the disease in vitro, and for use in potential transplantation therapy in humans.
Robert H. Baloh, MD, PhD