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Neurological injury frequently interrupts connections while sparing nerve cells themselves. Spinal cord injury (SCI) is the epitome of a disconnection syndrome, in which surviving neural tissue fails to function due to lost communication above and below 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 circuity 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 chronic in vivo imaging of neuronal connections, genetic alteration of mice, and induction of surgical lesions resembling clinical SCI and stroke. In particular, we have found that the Nogo Receptor (NgR1) pathway mediating myelin inhibition of axonal growth plays a role in titrating anatomical plasticity in the adults CNS.
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 receptor ligand binding assays, expression cloning, electrophysiology, mouse genetics, and mouse behavior to study these pathways.
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NATURE COMMUNICATIONSno. 1 (2024)
Nature Communicationsno. 1 (2024): 1-23
bioRxiv : the preprint server for biology (2023)
Alzheimer's research & therapyno. 1 (2023): 1-25
medRxiv (Cold Spring Harbor Laboratory) (2023)
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Le Zhang, Chuan Hua He,Sarah Coffey, Dominic Yin,I-Uen Hsu,Chang Su,Yixuan Ye,Chi Zhang,Joshua Spurrier,LaShae Nicholson,Carla V Rothlin,Sourav Ghosh,
medRxiv : the preprint server for health sciences (2023)
Elisa M Howard,Stephen M Strittmatter
Current opinion in neurologyno. 6 (2023): 516-522
Bridget Shafit-Zagardo,Simone Sidoli,James E. Goldman,Juwen C. DuBois,John R. Corboy,Stephen M. Strittmatter,Hillary Guzik,Ukuemi Edema,Anita G. Arackal,Yair M. Botbol, Emilio Merheb, Rashed M. Nagra,
Cellsno. 13 (2023): 1734-1734
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