Joey Nichols
Program: Molecular Genetics and Genomics
Current advisor: Jeffrey Milbrandt, MD, PhD
Undergraduate university: Gonzaga University
Research summary
SARM1, a TIR domain-containing protein, is a metabolic sensor that triggers axon degeneration when the NAD+:NMN ratio drops too low. This sensor is typically kept in the ‘off’ position in healthy neurons due to a high NAD+:NMN ratio, but when this ratio drops, SARM1 undergoes a conformational change and the TIR domain hydrolyzes NAD+, rapidly depleting the cell of energy and triggering axon degeneration. This activity has positioned SARM1 as the ‘central executioner’ of axon degeneration following axonal injury (i.e. axotomy).
Much of the axon degeneration in humans is not due to axonal injury and is instead the result of cumulative insults due to aging, chronic disease, and chronic inflammation. I hypothesize that SARM1 is involved in axon degeneration observed in aging phenotypes and that inflammatory pathways interact with SARM1 to cause disease.
Graduate publications