The mechanisms regulating motor neuron cell death in amyotrophic lateral sclerosis (ALS) and other motor neuron diseases are unknown. However, since the year 2000 many genetic mutations that cause ALS and cellular pathways that contribute to the disease process have been discovered and characterized in model systems of ALS. A challenge of using model systems to discover and study the pathways believed to be relevant to the human disease stems from uncertainty about how accurately the models reflect the human disease. Drugs that were effective in rodent models of ALS have failed in human clinical trials. Our laboratory is at the forefront of using human patient samples to discover biochemical alterations that occur early in the disease process that reflect the underlying pathology of the disease and of using cell culture-based systems to further explore the pathways that we know are affected in ALS patients. We hope to translate these findings into improved drug therapies for ALS patients.
We have used unbiased proteomic technologies to discover proteins and pathways that are altered early in ALS patients, and we are examining how these proteins and pathways modulate motor neuron cell death in various in vitro model systems. We strive to reconcile the findings obtained from our model systems with the findings in patient samples. A number of our research projects involve collaborations between scientists and clinicians at medical research centers throughout the United States.