Research Areas

The Rowitch Lab works on breakthrough research projects that have yielded insights in the following domains.

In the NIH PO1 program project that Rowitch directed, we identified widespread neuronal migration in the human neonatal brain and the impact of hypoxia on developing oligodendrocytes and neurons as a means to identify mechanisms that underlie cerebral palsy and intellectual disability. In collaboration with the Alvarez-Buylla lab, we showed a novel population of late-migrating neurons in the human neonatal forebrain. The “medial migratory stream” is a derivative of the rostral migratory stream, which appeared to feed the ventromedial prefrontal cortex.

While MS is classically understood as an autoimmune disease responsive to immunomodulatory therapies, progressive MS remains refractory to current treatments, highlighting the critical need to understand the fundamental neurodegenerative processes underlying this phase. Rowitch identified roles for the Wnt pathway in the regulation of oligodendrocyte differentiation during development and white matter repair. In studies using single nuclei RNA Seq of human brain samples from MS patients, spatial transcriptomic (‘LaST’) and animal studies, Rowitch established that upper cortical layer CUX2+ neurons are selectively vulnerable to DNA damage in MS and also during chemotoxic and developmental stress.

Rowitch and colleagues identified that bHLH proteins Olig1 and Olig2 genes are essential regulators of oligodendrocyte specification from restricted progenitor domains in the ventral neural tube. He demonstrated that morphogen-driven embryonic CNS patterning generates multiple functionally distinct glial populations with region-restricted identities and that cross-antagonistic interactions between Olig2 and SCL regulate early oligodendrocyte versus astrocyte cell fate specification, helping to explain macroglial diversity. Using fate mapping and genetic analysis, Rowitch demonstrated that region-restricted astrocyte progenitors are instructed by developmental cues to support regionally distinct neural circuits, such as ventral horn astrocytes expressing Sema3a, which is required for the survival and optimal function of fast alpha spinal motor neurons and peak strength.

First described over 150 years ago and affecting approximately 50 million people globally, the causes of cerebral palsy remain poorly understood. Rowitch has defined key mechanisms of OPC maturation arrest that fundamentally limit remyelination capacity and contribute to permanent neurological deficit. He defined key mechanisms linking hypoxia-inducible pathways, angiogenesis, Wnt signaling and oligodendrocyte precursor (OPC) differentiation in neonatal white matter injury. In collaboration with pathologist Hannah Kinney, he identified OPC maturation arrest as a key pathological feature and demonstrated that Wnt pathway activation serves as a critical regulator of OPC differentiation. Recent genetic studies intriguingly reveal that CTNNB1, encoding β-catenin, is among the most common lesions found in genetic forms of cerebral palsy.

Rowitch led a first-in-human clinical trial of a neural stem cell transplant for Pelizaeus-Merzbacher disease (PMD), a rare, X-linked genetic disorder affecting the central nervous system, causing abnormal myelin development in the brain and spinal cord.