Susan Ackerman's pioneering investigation of neurodegeneration draws on her training in classical genetics, molecular biology, and behavior. Ackerman is exploiting the power of mouse genetics to provide a whole new view of the molecular and genetic mechanisms of neurodegeneration, such as that underlying Alzheimer's disease, Parkinson's disease, and motor neuron disease.

Taking advantage of the tremendous diversity of mutant mice available at the Jackson Laboratory where she works, Ackerman begins her studies by identifying mutant mice with interesting neurological phenotypes. She then works to identify the mutated genes responsible for those phenotypes, and has used this strategy to reveal several genes with critical roles in neuron protection and destruction in the aging central nervous system. Using the tools of cell and molecular biology and her knowledge of neuroanatomy, Ackerman probes deeper, yielding a clearer picture of how the products of those genes contribute to the development and maintenance of a healthy nervous system.

In one of her first major accomplishments, Ackerman demonstrated that a mutation in a gene called Unc5c is responsible for defects in the development of the cerebellum—the part of the brain responsible for motor control. Through further experiments, she revealed that in a developing embryo, Unc5c orchestrates the construction of boundaries within the cerebellum, and also guides axon development in the corticospinal tract—a massive bundle of approximately 1 million axons descending from the brain.

More recently, her work on a mutant mouse called harlequin has provided a new genetic model of neurodegeneration due to oxidative stress. The harlequin mouse experiences progressive loss of muscle control and vision due to death of neurons in the cerebellum and the retina. Harlequin mice have a mutation in the apoptosis-inducing factor (Aif) gene, which produces a protein that regulates levels of free radicals in certain neurons in the brain and retina. The Aif gene was thought to play a role in cell death, but Ackerman's work demonstrated that it is needed for neuron survival. She is now exploring the role of the Aif gene in development of different neurons and is pairing the harlequin mutation with mutations in other oxidative stress pathways.