The main focus of my research is the question how pluripotent stem cell technology can be harnessed to understand the function and dysfunction of neural circuits which control motor behaviour, and how stem cell-derived tissue can be used to regenerate neuromuscular circuits in adult mammalian animal models and, ultimately, in human patients. To this end, my group embarked on projects aimed at:
i) Assembling neuromuscular circuits from stem cell-derived, defined cell populations to study normal development and degenerative disease processes such as Amyotrophic Lateral Sclerosis (ALS) in vitro.
ii) Restoring muscle function affected by neuromuscular disease with a new type of stem cell-based optogenetic pacemaker device.
2) ALS as a neurodevelopmental disorder
ALS is a neurological disease which leads to loss of nerve muscle-connectivity, degeneration of motor neurons and, as a result, muscle paralysis. Most patients die within 3-5 years of diagnosis, and currently, there is no effective treatment for ALS. Though patients typically show clinical symptoms as adults, emerging evidence suggests that initial abnormalities in synapse homeostasis and cell signalling occur much earlier during embryonic and/or postnatal development. This suggests that understanding the abnormal development of motor circuits may help understand the disease mechanism and may contribute to future therapies. My group and our collaborators are studying such early event in the cellular pathology of ALS. Our main experimental tool is a model of neuromuscular circuits, assembled in vitro from normal and patient-derived induced pluripotent stem cells.