Lu Lab

Myelination in the CNS by oligodendrocytes is critical for normal neuronal function. Failure of myelin regeneration causes demyelinating diseases such as multiple sclerosis, which affect 2 millions people worldwide. We are exploring the roles of histone deacetylases (HDACs), chromatin remodeling factors such as Brg1 complexes, and non-coding RNAs such as microRNAs in the control of myelination and remyelination in the CNS and PNS. We are also investigating the small molecules that regulate the activity of chromatin remodeling enzymes in controlling myelination and myelin repair.

Chromatin remodeling control of CNS myelination.

We are utilizing single cell expression profiling approaches to identify the genetic programs regulating progenitor/stem cell differentiation potentials for oligodendrocyte formation. We seek to determine mechanisms controlling oligodendrocyte precursor (OPC) proliferation and differentiation after acute and chronic demyelinating injury.

Oligodendrocytes generated from progenitor cells.

We are dissecting the signaling pathways and transcriptional mechanisms that mediate the formation of brain tumors including glioma and medulloblastoma, the most common malignant brain tumor in children. In addition, we seek to identify tumor initiating cells and signaling molecules that control tumor cell growth and proliferation.

Medulloblastoma formation in the mouse cerebellum.

Schwann cells are responsible for myelination in the PNS. Myelin defects are associated with neurodegenerative diseases including inherited peripheral neuropathies. Abnormal development of Schwann cell precursors contributes to the formation of peripheral nerve tumors including neurofibroma and Schwannoma. Schwann cell development and myelination are actively studied to identify the underlying mechanisms that lead to peripheral neuropathies and peripheral nerve tumors.