Position title: Professor
Phone: (608) 262-1016
Ph.D. in Pharmacology, University of Washington-Seattle
The overall goal of our research is to investigate the cellular and molecular mechanisms regulating microglial phenotype and function as they contribute to neural pathology and recovery in chronic neuroinflammatory disorders. We have particular interest in understanding how microglial reprogramming during fetal development impacts CNS development and neuroimmune activities later in life. Our observations of respiratory and behavioral deficits in male offspring of mothers exposed to a model of gestational sleep disordered breathing, and the involvement of microglia in these deficiencies, indicates that intercellular communication with microglia is essential for health CNS function, and has immense clinical significance given the growing incidence of mothers with sleep disordered breathing during pregnancy and the negative outcomes on their offspring during development. Our recent evidence implicates a critical role for epigenetic processes (e.g. histone demethylation and microRNAs) in the mechanisms employed by intermittent hypoxia, a hallmark of maternal sleep disordered breathing, on microglial gene priming and reprogramming during fetal development. We utilize RNA-Seq, ChIP-Seq and 10X Genomics approaches to study the mechanisms whereby microglia contribute to sexual dimorphisms in behavioral and neuroplasticity outcomes, and the roles they play in regulating neuronal spine morphology and neuroplasticity in different CNS regions. We have developed powerful and novel flow cytometry and cell sorting tools with which to study specific microglial phenotypic populations in vivo, from which nucleic acids (DNA, mRNA and miRNAs) can be isolated for subsequent transcriptional regulation studies and Next-Gen sequencing approaches. These investigations are complemented by biochemical signaling studies in primary cultures, electrophysiological approaches to assess neuroplasticity in situ, and rodent behavioral assays to test cognitive function.
Microglia, sexual dimorphism, signal transduction, fetal programming, gene transcription