Johns Hopkins School of Medicine

Disease modeling of peripheral neuropathies with human pluripotent stem cells

Human induced pluripotent stem cells (hiPSCs) now provide unprecedented opportunities for cell replacement approaches, disease modeling and drug discovery in patient-specific manner. In particular, Lee lab is focusing on neural crest lineage (including peripheral neurons, Schwann cells, melanocytes) and skeletal muscle tissue, in terms of their fate determination processes as well as relevant genetic disorders.

Previously, Lee group studied a human genetic disorder (Familial Dysautonomia, FD) with hiPSCs, and found that FD-specific neural crest cells have low levels of genes needed to make autonomous neurons—the ones needed for the “fight-or-flight” response. Moving forward, as an effort to discover novel drugs, they performed high throughput screening with a compound library using FD patient-derived neural crest cells. Further they recently established a direct conversion methodology, turning patient fibroblasts into ‘induced neural crest (iNC)’ that also exhibit disease-related phenotypes just as the FD-hiPSC-derived neural crest. In addition, currently they study the fate determination processes of other neural crest lineages, including nociceptive neurons, pruriceptive neurons, sympathetic neurons and Schwann cells.

Now Lee group is extending their research interest to neural crest’s neighboring cells, somite. Using multiple genetic reporter system, they identified sufficient cues for directing hiPSCs into somite stage, followed by skeletal muscle lineages. This novel approach can straightforwardly apply to muscular dystrophies (e.g., Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy), resulting in expandable myoblasts in patient-specific manner.