Our Research

The O’Neil Lab’s focus is on understanding how the structure of protein aggregates affect the cellular outcomes of neurodegenerative disease.

Neurodegenerative diseases are unique in that they each affect a specific class of neuron. To access these highly specialized cell types, we use human induced pluripotent stem cells (iPSCs) differentiated into the desired neuron type to model disease.

Another unique aspect of neurodegeneration is that almost all of these diseases have not only cell specificity, but also a protein aggregate phenotype. As examples, in Alzheimer’s disease amyloid beta aggregation causes the hallmark plaques in patient’s brains while aggregating alpha synuclein causes the formation of Lewey Bodies seen in Parkinson’s disease.

The lab is currently interested in understanding how the aggregation of superoxide dismutase (SOD1) is involved in the death of motor neurons as seen in ALS.  We will be harnessing the power of ALS-patient iPSCs which harbor SOD1 mutations to: define the parameters under which SOD1 aggregates in the cell, biochemically characterize the SOD1 aggregates themselves, and elucidate how aggregation leads to motor neuron death.