Identify mediators of neuronal susceptibility in amyotrophic lateral sclerosis

Despite tremendous efforts over the last two decades, no good amyotrophic lateral sclerosis (ALS) markers exist to identify who is at greater risk to develop ALS, allow early diagnosis, predict the course of disease and support clinical trials. Importantly, the reason why some brain regions are affected in ALS while others are spared is still enigmatic. We hypothesize that mutations appearing early during embryonic development and DNA damage acquired while aging lead to altered regulation of many important biological mechanisms and make motor neurons of the motor cortex and spinal cord more susceptible to degenerate. To test our hypothesis, we will use state-of-the-art technology and informatic approaches to characterize ALS affected and unaffected motor neurons and identify critical genetic and epigenetic variations that drive cell death. Affected and unaffected motor neurons will be compared to one-another as well as to autopsied tissues from pathologically normal individuals. By doing this, we hope to identify potential markers of motor neuron degeneration unique to ALS patients.