Neurons are extremely specialized cells. They can generate intense electrical activity, maintain highly complex morphologies, and survive our entire lifetimes. Moreover, neurons are incredibly diverse, exhibiting a wide range of activity states, shapes, and sizes. These specializations confer different needs and liabilities to neurons, which they must address by adapting their molecular pathways to maintain homeostasis. When these pathways are perturbed, cell death may ensue. Differential neuronal death is a hallmark of neurodegenerative disease, but the mechanisms underlying this remain unresolved. Our long-term goal is to define neuronal adaptations in metabolism and signaling and understand how they contribute to disease.
We seek to address three major questions:
(1) What are the metabolic needs and vulnerabilities of neurons across the brain?
(2) How are core signaling and metabolic pathways remodeled to support different neuronal classes?
(3) Why do some neurons die in neurodegeneration while others live?
We will systematically address these questions with a multidisciplinary approach spanning molecular biology, biochemistry, neurobiology, and animal behavior. Knowledge from this research will have broad implications for our understanding of neuronal function in health and disease.
