Primary Department Affiliation: Cell, Developmental and Integrative Biology
Primary Research Area: Ion Channels and Synaptic Function
Neurodevelopment and Developmental Disabilities
Neurodegeneration and Neurodegenerative Disorders
Neurotransmitter and Neurotrophin Receptors and Cell Signaling
The focus of my research is to enhance our understanding of the role of astrocytes in brain and spinal cord function. Astrocytes are the most numerous cells in the central nervous system yet the role of astrocytes in neurodevelopmental disorders and injury, particularly pediatric injury, is highly understudied.
My work focuses on two essential functions of astrocytes; buffering of extracellular K+ and glutamate. These functions are thought to be largely mediated by two astrocytic proteins, Kir4.1, an inwardly rectifying potassium channel and excitatory amino acid transporter, GLT-1. These two proteins function to dampen neuronal excitability. Following injury, persistent alterations in the biophysical properties of astrocytes hinder their ability to perform these basic altruistic functions. The resulting dysregulation of extracellular K+ and glutamate are associated with increased neuronal excitability and changes in synaptic physiology and plasticity in the adult. In the developing central nervous system, loss of these functions may profoundly impact neuronal development. Surprisingly, little is known regarding the regulation of either protein in the normal developing brain, following injury or during abnormal development.
Our current research projects span from understanding how Kir4.1 and GLT-1 transcription and translation are being regulated during normal development, to how each is maintained in the adult brain and understanding changes in this regulation in pathological conditions. We are particularly interested in how reduced extracellular K+ and glutamate regulation in the immature brain impacts neuronal development. To do this work requires a multitude of techniques. To study protein expression we employ functional assays such as electrophysiology and glutamate uptake assays, in addition to protein biochemistry. Confocal and wide field fluorescent microscopy is used to visualize and localize protein in brain slices and in cultured cells. Quantitative PCR is used to examine transcript levels and we are currently implementing epigenetic techniques to investigate mechanisms of transcriptional regulation. To perform these experiments we utilize tissue derived from several animal models, primary astrocyte and neuron cultures and human autopsy and surgical resection tissue.