Retrotransposon Reactivation in Neurodegenerative Disease
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that causes complete paralysis and eventual death from the rapid and progressive loss of motor neurons. While a number of inherited mutations have been identified as causing ALS, the vast majority of patients have no known causal mutation or family history of disease. My lab has recently partnered with the NYGC ALS Consortium to undertake a large-scale integrated analysis of molecular alterations in ALS patients. The scale of this dataset allowed for a clean separation of ALS patients into a small set of distinct subtypes. One of these ALS subtypes involves the reactivation of endogenous retrotransposons, viral-like genomic parasites that normally lay dormant in the genome. This proposed study will develop novel machine learning software to systematically identify the genetic factors and molecular mechanisms that lead to motor neuron cell death, with a particular focus on retrotransposon reactivation.