Vascular Physiology
Capillary networks and have traditionally been viewed as passive sites for gas and nutrient exchange and waste removal. However, considering the vast area of the brain capillaries, which constitute ~90% of all vessels in the entire vascular landscape, the potential of these microvessels to serve sensory and signaling functions comes into sharp focus. Notably, their high density and close proximity to neurons ideally position capillaries to act as sensors of local signals from surrounding neurons and glia. Critically, a wide range of neurological disorders, including ischemic and hemorrhagic small vessel diseases, dementia, migraine, and age-related cognitive decline, exhibit deficits in cerebral blood flow. The enormity of the coverage area of brain capillaries, comprising pericytes and endothelial cells, can be more fully appreciated by direct visualization (see images below).
The brain vasculature can respond to neuronal and glial signals and regulate blood flow through the activation of various receptors and ion channels. However, our understanding of the repertoire of ion channels in pericytes and capillary endothelial cells and the properties governing the propagation and amplification of signals between these cells remains incomplete. This gap in our knowledge obscures our overall understanding of blood flow regulation in the brain and how diseases may affect blood flow and brain health, thus representing a fruitful research area for many years to come.
Areas of Research
Mechanisms of microvascular function/dysfunction in the meninges
Sensing and signaling roles of vascular ion channels in health and small vessel disease
Integrative Physiological Approach
Single-cell electrophysiology and calcium imaging.
Studying isolated native cells provides a detailed understanding of signaling that occurs in distinct brain vascular cell types, such as pericytes, endothelial cells, and smooth muscle cells.
Observations of vascular reactivity, membrane potential, and calcium signaling using intact tissues.
Using isolated intact vessels from various tissues, we can evaluate mechanisms of constriction and dilation in a stringently controlled environment. We also utilize the pressurized retina technique (above) to examine vascular responses in an intact CNS environment while maintaining control over intravascular pressure.
Integrating mechanistic observations in vivo.
The lab utilizes sophisticated genetic models and imaging techniques to probe mechanisms of blood flow delivery and vascular homeostasis in anesthetized, awake, and freely behaving animals. Some examples of this include functional ultrasound imaging of whole brain blood delivery (above) and two-photon imaging (below)
The lab utilizes patch clamp electrophysiology, high resolution/speed confocal and fluorescent imaging, intracellular voltage recordings, functional ultrasound, and two-photon imaging in cortical and retinal tissue. Pictures and descriptions of the equipment are coming soon (still building most of them)!