Return to list Beth Stevens, PhD

Investigator

Beth Stevens, PhD

Title

Assistant Professor of Neurology, Harvard Medical School
Assistant in Neurology, Boston Children’s Hospital

Department

Neurology

Address

Boston Children's Hospital
Center for Life Sciences Rm 12257
Boston, MA 02115

Phone

617-919-2979

Email

beth.stevens@childrens.harvard.edu

URL

http://www.childrenshospital.org/researchers/beth-stevens

Biography

Beth Stevens is interested in interactions between the two fundamental cell types of the nervous system, neurons and glia. Her laboratory seeks to understand how neuron-glia communication facilitates the formation, elimination and plasticity of synapses—the points of communication between neurons—during both healthy development and disease.

They focus on the role of neuron-glia and neural-immune interactions in the patterning of neural circuits. Her lab and their collaborators have identified an unexpected role for glia and components of the innate immune system in synaptic pruning. They found that astrocytes induce neuronal expression of complement C1q, the initiating protein of the classical complement cascade (which tags unwanted cells and debris for elimination in the immune system). C1q and downstream complement proteins target synapses and are required for synapse elimination in the developing visual system. Importantly, they found that C1q becomes aberrantly upregulated and is relocalized to synapses in the early stages of glaucoma, suggesting that a similar elimination mechanism may be in place during both healthy central-nervous-system (CNS) development and neurodegenerative diseases.

Their ongoing studies are directed toward defining the cellular and molecular mechanisms underlying synapse elimination during health and disease, with emphasis on the role of complement in this process. In addition to their interest in CNS neurodegenerative diseases, they are currently collaborating with other laboratories to further probe the potential link between complement proteins and synapse loss in the pathogenesis of epilepsy and neurodevelopmental disorders.

One current goal is to understand how synapses in the CNS are selectively targeted for elimination. Why does one synapse get eliminated while a nearby synapse stays intact? Our recent findings suggest that microglia—the immune cells of the CNS—may play an important role in the elimination process.

They are also interested in identifying the activity-dependent and molecular cues that regulate expression of complement proteins in the developing and diseased brain, and in determining the specific synaptic sites at which these proteins act. How might glial-derived signals impact other developmental processes, such as synaptogenesis and the myelination of axons? They employ a combination of live imaging, molecular, biochemical and neuroanatomical approaches to address these and other mechanistic questions.

Research
R01 NS071008
R01 NS092578