If interested in a position please contact Dr. Landreth.
As a geneticist deeply fascinated with the brain and neuroscience I am interested in the genetic developmental disorders that affect cognition and behavior in humans. I use mouse models of human disorders, such as the 16p11del mouse model of Autism, to elucidate basic mechanisms of brain development and how their disregulation leads to aberrant brain function. Specifically, I am interested in cortical progenitor cells and the signals that regulate their spatial and temporal proliferation and how this precisely orchestrated developmental process contributes to pathogenesis when it is not executed properly.
One of the pathways genetically implicated in brain development is the MAP Kinase Pathway, with ERK1 and ERKs being the final effector kinases. The ERKs are involved in cell proliferation, differentiation, as well as learning and memory. Neuro-cardio-facial cutaneous (NCFC) syndromes and some genetic forms of Autism arise from mutations in the elements of the Map Kinase Pathway and are associated with cognitive impairment and psychiatric disease. All of the above are caused by early perturbations in CNS development. Since ERK activity is highly present in the developing brain I have been working on elucidating of precise mechanisms by which ERKs regulate brain development and how congenital mutations that alter ERK signaling disrupts cortical development resulting in disease.
My most recent studies concentrate on pharmacological rescue of aberrant ERK signaling in mouse models of genetic disorders such as autism.
My research interests are macrophage and microglia biology and neuroinflammation in the context of aging and Alzheimer’s Disease. My research has included work on the mechanism of action of the RXR agonist, bexarotene, in a mouse model of Alzheimer’s disease (APP/PS1). My publication in the Journal of Neuroimmune Pharmacology in 2015 showed that ABCA1-mediated lipidation of ApoE was necessary for the clearance of soluble amyloid beta from the hippocampus of APP/PS1 mice. My current work is investigating the effects of microglial elimination following treatment with a CSF1R antagonist on amyloid pathology, neuronal loss, and cognitive ability in the 5xfAD mouse model. Ongoing and future projects concern the dynamic influence of amyloid beta on neuronal circuits involved with neuropsychiatric deficits in young (pre-plaque-depositing) APP/PS1 mice.