Dori Schafer earned her Bachelor’s degree in Neuroscience and Behaviour from Mount Holyoke College in 2001. She attended graduate school at the University of Connecticut Health Center in Matthew Rasband’s lab where she used rodent models to study neuron-glia interactions regulating assembly and maintenance of functional, polarized domains along the axon, nodes of Ranvier and axon initial segments. Upon completion of her PhD in 2008, she began her postdoctoral training in the laboratory of Beth Stevens at Boston Children’s Hospital. While in the Stevens lab (2008-2014), she studied the role of microglia, the resident CNS myeloid-derived cell, in mammalian synapse development and plasticity. She was hired in 2015 as a tenure-track Assistant Professor in the Department of Neurobiology at The University of Massachusetts Medical School. Her laboratory utilizes a combination of molecular biology and high resolution static and live imaging to understand how neurons and glia communicate with one another to regulating synapse development and plasticity.
Microglia-Synapse Interactions Regulating Neural Circuit Development, Plasticity, and Dysfunction. The nervous and immune systems are comprised of vastly different cell types long thought to perform separable and distinct physiological functions. Unexpectedly, these seemingly disparate systems are, in fact, working in concert. At the center are microglia, the resident central nervous system (CNS) macrophages, which were recently identified by us and others as key regulators of synapse number in the developing brain. Specifically, we identified that microglia regulate the elimination of excess synaptic connections that form in the developing rodent visual system by engulfing a subset of less active synapses. These results have changed how we think about microglia function (~5-10% of brain cells) and the importance is emphasized in devastating neuropsychiatric disorders (e.g. autism and schizophrenia) as well as neurodegenerative diseases (Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, etc.) where to few or too many synaptic connections coupled with abnormally reactive microglia are characteristic features and, perhaps, causative in disease. The overall goal of my research is to achieve a deep understanding of how microglia regulate synapse development, maintenance, and plasticity in the healthy brain and determine whether these mechanisms are dysregulated in disorders of the nervous system. The primary disorders we are currently focused on include autism, schizophrenia, ALS, and multiple sclerosis. We are now focused on the following main questions:
1) How do microglia respond on a cellular and molecular level to changes in neural activity and sensory experience ?
2) Are microglial necessary for remodeling of neural circuits in response to changes in sensory experience?
3) Do microglia regulate abnormal synaptic connectivity in neurological disease?
To address these questions, the lab has developed novel strategies to image glia-synaptic circuit interactions by high resolution static imaging as well as 2-photon in vivo live imaging in behaving mice. In addition, we have implemented cutting-edge molecular genetic techniques to dissect microglia-specific mechanisms underlying synapse development, plasticity, and function.
For more information please visit our website: https://www.schaferlabumms.com