Taub Institute: Genomics Core
AN NIA-FUNDED ALZHEIMER'S DISEASE RESEARCH CENTER

 

Columbia University
Medical Center
Neurological Institute

710 West 168th Street, 3rd floor
(212) 305-1818


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About Us

Taub Faculty


 Russell Nicholls, PhD

Russell Nicholls, PhD

Assistant Professor of Pathology & Cell Biology

Email: rn95@cumc.columbia.edu
Tel: 646-379-1812

Research Summary:

I am interested in the molecular mechanisms that regulate neuronal activity and how dysregulation of these mechanisms leads to nervous system dysfunction and disease including Alzheimer's disease, neurodegeneration resulting from traumatic brain injury, and the autism spectrum disorder, fragile X syndrome. To pursue these topics, I utilize a multidisciplinary approach involving behavioral, electrophysiological, molecular, and biochemical approaches in genetically modified mouse models and cultured cells.

One area of my current research focuses on understanding the role of protein phosphatase 2A in Alzheimer’s disease and related forms of neurodegeneration. Using genetically modified mice that target PP2A regulation, I found that promoting demethylation of the PP2A protein increases the sensitivity of mice to electrophysiological and cognitive impairments caused by beta-amyloid and tau protein, suggesting that impaired PP2A signaling could contribute to the development of Alzheimer's disease by enhancing the pathological response to beta-amyloid and tau. Conversely, I found that promoting PP2A methylation protects animals from beta-amyloid and tau-induced impairments, identifying this pathway as a potential therapeutic avenue for the prevention or treatment of Alzheimer's disease. In ongoing experiments I am pursuing the therapeutic potential of this pathway and seeking to understand the molecular basis for the effect of PP2A signaling on beta-amyloid and tau sensitivity.

A second area of research focuses on the role of the retinoic acid receptor-gamma (RXRγ) protein in group I metabotropic receptor signaling and its potential involvement in molecular pathways contributing to fragile X syndrome. I found that loss of RXRγ reduced group I metabotropic receptor signaling suggesting a molecular basis for the interaction between these two pathways that may be important for coordinating their roles in homeostatic and activity-dependent synaptic plasticity. Since hyperactive group I metabotropic receptor signaling is thought to contribute to fragile X syndrome, these data also suggest that RXRγ may represent a novel therapeutic target for this disorder. Experiments are currently underway to test the potential of RXRγ as a therapeutic target for fragile X syndrome and to further understand the molecular basis of the interaction between these two pathways.

Education and Training:

PhD: Harvard University, Cambridge, MA
BS: Cornell University, Ithaca, NY




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