Gliosis was observed hundreds of years ago. It is tightly associated with many neurological diseases, including stroke, traumatic injury, multiple sclerosis (MS), Alzheimer’s Disease (AD), and Amyotrophic Lateral Sclerosis (ALS). In recent years, glial abnormality has been shown to occur before the onset of many neurological diseases, suggesting that glial cells may drive disease progression. Therefore, probing glial cells provides a unique angle in understanding and possibly treating these diseases. We are devoted to understanding the mechanisms underlying oligodendrocyte-associated diseases, including demyelinating diseases like neonatal white matter injury and multiple sclerosis. We have identified a few molecular handles and have established several animal models to address demyelination and remyelination mechanisms. In addition, we are interested in non-canonical oligodendrocyte diseases, including psychiatric disease and AD in which oligodendrocyte-specific genes are mysteriously dysregulated.