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Sackler School of Graduate Biomedical Sciences

Michele Jacob

Professor of Neuroscience
Michele Jacob

Michele Jacob

Professor of Neuroscience

Office phone: 617-636-2429
Campus: Boston
Office: Stearns 327
Laboratory: 
Arnold 305
Education: 
BS, Biology, City College of New York
PhD, Cell Biology, Yale University
Postdoctoral Training, Columbia University; University of California, San Diego
Research synopsis: 

Autism spectrum disorders (ASD) and intellectual disabilities (ID) are highly prevalent developmental brain disorders. Knowledge of the underlying pathophysiological changes is essential for developing therapeutic strategies. Emerging evidence from human genetic studies suggests that several of the risk genes for ASD, ID, and seizures (pediatric epileptic encephalopathies) converge on the adenomatous polyposis coli protein (APC), β-catenin (β-cat), canonical Wnt signaling pathway. However, direct tests that malfunction of this pathway can cause these disorders, and knowledge of the underlying mechanisms, are largely lacking. To address this important question, we have generated several novel mutant mouse lines with gain- or loss- of function in this pathway in neurons of the brain. We are determining the pathophysiological changes on behavioral, molecular, synaptic, and circuit levels. Additionally, we are using pharmacological approaches to test novel molecular targets with potential to ameliorate ID, ASD and seizures and thereby advance the design of effective therapeutic interventions.

Our studies have identified APC as a key regulator of excitatory synaptic maturation and plasticity in both peripheral and central neurons. APC’s synaptic functions were undefined prior to our work. Our current findings are identifying additional new roles for APC and β-cat in synaptic plasticity required for learning and memory formation. Our results are providing critical insights into molecular etiologies that cause learning impairments of different severities, autism-like behaviors and chronic seizures.

Lab members: