Oligodendrocytes, the myelinating cells of the central nervous system, have extraordinary demands for oxygen, nutrients, and metabolic substrates to support the production of myelin proteins and proteolipids, as well as to provide trophic support to axons. These requirements suggest that establishing a functional cerebrovascular network—which ensures adequate blood supply and oxygenation—is a critical regulatory step in white matter myelination. Importantly, this vascular–metabolic dependency is also central to successful oligodendrocyte regeneration and remyelination, a process that is impaired in multiple sclerosis (MS) where inflammatory injury, altered cerebral perfusion, and vascular dysfunction can limit the ability of oligodendrocyte progenitors to differentiate and repair damaged myelin. Consequently, white matter dysfunction and myelination deficits are increasingly implicated not only in neonatal brain injury and neurodevelopmental disorders with vascular pathology, but also in chronic demyelinating diseases such as MS, where both injury and insufficient vascular support contribute to remyelination failure.

 

The Chavali Lab is interested in understanding the cellular and molecular mechanisms that regulate oligodendroglial and cerebrovascular development, and in applying these insights to better understand white matter injury in premature birth, congenital heart disease (CHD), multiple sclerosis (MS), and leukodystrophies. We employ a wide range of genetic and injury models to mimic the pathophysiology of these conditions and aim to address the following questions:

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• How do disruptions in cerebral blood flow and/or oxygen delivery influence myelin synthesis and white matter function?

• What roles do oligodendroglial–endothelial cell interactions play during myelination and remyelination?

• How does impaired development of oligodendroglial precursor cells in neonatal brain injury affect the formation and function of neuronal circuitry?