Research Faculty

Address
630 West 168th Street,
P&S 12-510B
New York, NY 10032

Phone: 646-379-1812
Fax: 212-342-9096

rn95@cumc.columbia.edu
Education and Training
Ph.D., Harvard University, Cambridge, MA
B. S., Cornell University, Ithaca, NY

Affiliation
Taub Institute
Russell Nicholls, Ph.D.
Assistant Professor of Pathology and Cell Biology
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.
Selected Publications

Hue C.D., Cho F.S., Cao S., Nicholls R.E., Vogel E.W., Sibindi C., Arancio O., Bass C.R., Meaney D.F., and Morrison B., (2015) Time Course and Size of Blood-Brain Barrier Opening in a Mouse Model of Blast-Induced Traumatic Brain Injury. Neurotrauma (in press)

Teich A.F., Nicholls R.E., Puzzo D., Fiorito J., Purgatorio R., Fa M., Arancio O. (2015) Synaptic Therapy in Alzheimer’s Disease: A CREB-centric Approach. Neurotherapeutics 12:29-41.

Thualt S.J., Malleret G., Constantinople C.M., Nicholls R.E., Chen I., Zhu J., Panteleyev A., Vronskaya S., Nolan M.F., Bruno R., Seigelbaum S.A., Kandel E.R. (2013) Prefrontal Cortex HCN1 Channels Enable Intrinsic Persistent Neural Firing and Executive Memory Function. J Neurosci 33:13583-99.

Nicholls R.E., Alarcon J.M., Malleret G., Carroll R.C., Grody M., Vronskaya S., and Kandel E.R. (2008) Transgenic mice lacking NMDAR-dependent LTD exhibit deficits in behavioral flexibility. Neuron 58: 104-17.

Bailey C.P., Nicholls R.E., Zhang X-L., Muller W., Kandel E.R., and Stanton P.K. (2008) Gαi2 inhibition of adenylate cyclase regulates presynaptic activity and unmasks cGMP-dependent long-term depression at Schaffer collateral-CA1 hippocampal synapses. Learning and Memory 15: 261-270.

Nicholls R.E., Zhang X-L., Bailey, C.P., Conklin B.R., Kandel E.R., and Stanton P.K. (2006) mGluR2 acts through inhibitory Gα subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses. Proc. Nat. Acad. Sci. USA 103: 6380-6385.

Committees , Council, and Professional Society Memberships

Society for Neuroscience

top
 
 
Contact the Pathology Webmaster at PathWebMaster@columbia.edu