McGaugh Distinguished Seminar Series

Tuesday, March 31st, 2026 at 11:00am

The seminar will be In-Person.

Dr. Stephen M. Strittmatter

Vincent Coates Professor 
Departments of Neurology and Neuroscience, Yale School of Medicine

Cellular and Molecular Mechanisms of Protein Aggregate-Induced Damage in Neurodegeneration

Bio:

Throughout his career, Dr. Strittmatter has repeatedly moved from foundational work in neuroscience to understanding neurological conditions and subsequently to clinical trials. Dr. Strittmatter has a long-standing interest in ligand–receptor interactions and signal transduction in translational neuroscience. He developed expertise in the biochemistry of neuronal receptors during MD/PhD training with Solomon Snyder at Johns Hopkins. He pursued Neurology residency training at Massachusetts General Hospital under the guidance of John B. Martin, Raymond Adams, and C. Miller Fischer. His clinical practice included an early focus on Movement Disorders working with John Growdin and Kenneth Marek. More recently, he founded the Yale Memory Disorders Clinic leading 7 neurologists plus support personnel.
    After Residency training, he developed an interest in the molecular biology of axon growth during a Fellowship with Mark Fishman. In his own laboratory at Yale, the mechanisms of axon guidance were the first focus, and insights into the molecular mechanisms of Semaphorin action during brain development were revealed. This led to an interest in the molecular pathways that inhibit fiber growth and functional rewiring of healthy and damaged adult brain. His work included the identification of Nogo and its receptor NgR1. This pathway was shown to play a role in limiting recovery after spinal cord injury and stroke. Focus now is the study of brain plasticity and its modulation by NgR1 and by injury as well as unbiased discovery of pathways. Technically, he utilizes genome-wide shRNA and CRISPR screening, chronic in vivo imaging of neuronal connections, genetic alteration of mice and induction of surgical lesions resembling clinical trauma and stroke, as well as clinical trial testing. 
    Over the last decade, Dr. Strittmatter has also focused on pathophysiological ligand–receptor pairs in the degenerative dementias, primarily Alzheimer’s disease (AD). The contribution of particular ligands to these pathologies had been identified by genetic methods, but their mechanism of action remained poorly understood. Dr. Strittmatter has focused on defining the pathophysiological action of Amyloid-beta (Aβ) peptide oligomers in AD, and on the role of secreted Progranulin in Fronto-Temporal Lobar Degeneration. For both of these molecules, interaction with the specific receptors on the neuronal surface is crucial. His investigations have led to the identification of PrP C and Sortilin as sites for Aß and PGRN, respectively. He has defined a molecular pathway from Aßo through PrP C to mGluR5 and Fyn/Pyk2 kinases leading to synaptic dysfunction in AD models. His laboratory utilizes receptor ligand binding assays, expression cloning, electrophysiology, genetics, single cell RNAseq, mouse behavior, fMRI, PET imaging and clinical trials to study these pathways. 
    Dr. Strittmatter is deeply committed to training and mentoring of developing scientists focused on Neural Repair and Neurodegeneration, with a particular emphasis on creating a supportive research environment. He leads a T32 institutional training grant. Within his own laboratory, Dr. Strittmatter has served as primary mentor at Yale for 45 postdoctoral fellows and 37 graduate students conducting thesis research. Of these, fully 26 have already gone on to full time faculty positions including Alyson Fournier, Fenghua Hu, Haakon Nygaard and William Cafferty.