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Stephen Strittmatter

Vincent Coates Professor of Neurology and Professor of Neuroscience; Chair, Neuroscience; Director, Kavli Institute for Neuroscience; Director, Cellular Neuroscience, Neurodegeneration and Repair; Director, Memory Disorders Clinic; Director, Yale Alzheimer's Disease Research Center

Contact Information

Stephen Strittmatter, MD, PhD, AB

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Research Summary

Neural Repair and Neuro-Degeneration

Neurological injury frequently interrupts connections while sparing nerve cells. Spinal Cord Injury (SCI) is the epitome of a disconnection syndrome, in which surviving neural tissue fails to function due to lost communication at the level of injury. For the organism to regain function, new pathways must form by growth of cut or surviving nerve fibers. Unfortunately, the growth of axons and the rearrangement of brain circuitry are extremely limited in the adult brain and spinal cord.

We focus on understanding the molecular pathways that limit fiber growth and functional rewiring of neuronal circuits during health and disease. Axonal growth encompasses both neural plasticity and repair. Technically, we utilize CRISPR-based genetic screens, single cell transcriptomic profiling, mutant mice and surgical lesions to model spinal cord injury. These activities support the development of novel therapies now in clinical testing.

In Alzheimer's Disease and several other neurodegenerative conditions, nerve cells are lost over time. Molecular contributors to this pathology have been discovered by genetic methods, but their mechanism of action has remained poorly understood. We have focused on defining the pathophysiological action of Amyloid-beta (Aß) peptide oligomers in Alzheimer's Disease, and on the role of secreted Progranulin in Fronto-Temporal Dementia. For both of these molecules, interaction with the specific receptors on the neuronal surface is crucial. We utilize utilize receptor ligand binding assays, CRISPR-based genetic screens, single cell transcriptomic profiling, mutant mice, histopathology, PET imabehavior and cryo-electron microscope to define these pathways. These novel approaches are being translated to clinical trials.


Research Interests

Alzheimer Disease; Axons; Dementia; Spinal Cord Injuries; Regenerative Medicine; Frontotemporal Dementia

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Selected Publications