BLRD Research Career Scientist Award Application

Abstract The main focus of our scholarly work has been conducting laboratory-based research into aging-relevant neurodegenerative diseases with a particular focus on neurodegenerative diseases impacting Veterans’ health. We have established a group of interdisciplinary researchers to identify genes and pathways involved in aging-related neurodegenerative disease for the purpose of developing small-molecule neuroprotective agents for neurodegenerative diseases impacting Veterans’ health. In particular our group investigates the molecular targets for intervention against tau and TDP-43 neurotoxicity in neurons. For this approach we employ a variety of model systems including transgenic C. elegans, transgenic rodent, and human cellular models of protein aggregation. These models are used to uncover genes playing a conserved role in neurotoxicity. We anticipate that work in model systems may provide insight into mechanisms of neurodegeneration in human disease. We can thus use these findings to formulate hypotheses of neurotoxicity and develop neuroprotective strategies accordingly. Our ultimate goal is to validate neuroprotective strategies using mammalian systems to de- risk future development of therapeutic approaches for conditions impacting Veteran’s health with a particular focus on Alzheimer’s disease and ALS (a service connected condition).