Glial and Epithelial Cells
Glia compose half of all brain cells. Strikingly, almost the entire surface of intracerebral vascular cells are covered by specialized astrocytic processes called endfeet. Endfeet play roles in ensuring blood-brain barrier integrity, forming a paravascular pathway for cerebrospinal fluid flux, and in controlling arteriolar diameter and blood flow. The exact contributions of astrocytes to blood flow control are a point of controversy - it has long been known that astrocytic endfeet can exhibit calcium elevations in response to neuronal activity, but whether these cause constriction or dilations of blood vessels, and whether these occur on a timescale appropriate for neurovascular coupling and functional hyperemia are points of debate. Thus, we are interested in determining the precise contributions of astrocytic signaling to brain blood flow control at the level of the capillaries and arterioles.
Choroid Plexus, Epithelial, and Ependymal Cell Function
The ventricular system is vitally important to overall brain health. Here, cerebrospinal fluid is produced (approximately 600 milliliters per day in humans), which then circulates through the ventricular system, over the brains surface, and then into the brain through the recently discovered glymphatic system. Cerebrospinal fluid plays many important roles – it provides a fluid cushion for the brain, sets the resting ionic concentrations which dictate neuronal function, and plays a critical role in ‘cleaning’ the brain to ensure ongoing healthy function. The ventricular choroid plexus, composed of cuboidal epithelial cells, is responsible for cerebrospinal production.
The ventricles are also lined by specialized glia called ependymal cells, a subgroup of which possess motile cilia. The beating of these cilia aids fluid convection through the ventricles and prevents unstirred layers from forming which would disrupt ionic concentrations.
Despite these essential roles, little is known of the contributions of ion channels, GPCRs and calcium signaling to choroid plexus function, or of the mechanisms through which ciliary beating is controlled, and how these processes are impacted by disease. We are thus investigating the ion channels and G-protein coupled receptors that regulate ciliary beat frequency, how neuronal activity influences ciliary beating, and how ciliary function is disrupted in dementia. We are also interrogating the mechanisms and roles of calcium signaling in choroid plexus function.
You can read more about these interests and the types of experiments we do by clicking on the images below.
We are actively seeking graduate students and postdocs. If you are interested in learning more about our research and potentially joining us, please get in touch!