In the Howell lab, we apply genetics and genomics approaches to identify fundamental processes involved in the initiation and early propagation of age-related neurodegenerative diseases, focusing on Alzheimer's disease, non-Alzheimer's dementia and glaucoma. Understanding these processes provides the greatest opportunity of therapeutic intervention. We are particularly interested in the role of non-neuronal cells including astrocytes, monocyte-derived cells (such as microglia), endothelial cells and pericytes.
In previous work, I applied novel genomics and bioinformatics strategies to identify new molecular stages of glaucoma that preceded morphological changes. Genetic knockout and/or pharmaceutical approaches showed that targeting the complement cascade and endothelin system significantly lessened glaucomatous neurodegeneration in mice. Our work with glaucoma continues in collaboration with Dr. Simon John, and we are also now applying similar genetics and genomics strategies to understand initiating and early stages of Alzheimer's disease, vascular dementia and other dementias. A major aim is to combine knowledge from human genetic studies with the strengths of mouse genetics to develop new and improved mouse models for dementias and make them readily available to scientific community.