Guthrie Research Lab
Kathleen Guthrie, Ph.D., is Professor, Department of Biomedical Science, Schmidt College of Medicine and Assistant Director of Education, FAU Brain Institute. Dr. Guthrie's research program focuses on neurodegenerative diseases and injuries that damage the adult brain, lead to loss of neurons, and ultimately some neural functions. Lost neurons cannot be replaced, though the possibility of using neural stem cells to accomplish this has received wide attention.
The Guthrie lab focuses on the brain's olfactory system, which has the unique ability to continuously replace neurons, both peripherally and centrally, under normal conditions, and following injury. Unlike most of the adult brain, the system maintains intrinsic neural stem cells that continuously generate new neurons throughout life. These newborn neurons replace those that are gradually eliminated by normal programmed cell death, resulting in adaptive circuit remodeling as the new neurons integrate and form synaptic connections.
By using the adult mammalian olfactory system as a model, we seek to study how these stem cell-derived brain neurons develop, what factors and conditions regulate their survival and functional integration, and how they are impacted by injury, neurodegenerative disease, or genetic mutations that cause neurodevelopmental disorders. Angelman Syndrome (AS) is a devastating genetic disorder on the autism spectrum characterized by intellectual impairment and seizures. The AS mutation eliminates neuronal expression of the ubiquitin ligase Ube3a. The role of this enzyme in normal neuron development, and the pathogenesis caused by its loss, is not well understood.
Using genetic mouse models, gene transfer into CNS stem cells, imaging techniques, 3D neuron structural analyses and behavioral assays, our current work tracks the development of new, adult-born neurons in the AS brain to determine what abnormalities arise, when these occur during the maturation/integration process, and how sensory function is impacted.