Projects
Visualizing the plumbing of the brain
To investigate how brain blood vessels grow, degrade, and respond to injury, we use rodent models paired with advanced imaging techniques (multi-photon microscopy), to visualize blood cell movement in the living brain. Our approach involves creating cranial windows, where a small section of skull is replaced with glass to provide direct optical access to the brain. By introducing dyes into the bloodstream, we label the plasma and generate "fluorescent angiograms," offering detailed insights into vascular dynamics and structure.
Dissecting the control of blood flow in
brain capillaries
ACerebral blood vessels are lined by a variety of cell types, each playing a unique role in regulating vascular function. Our lab focuses extensively on brain pericytes, a type of mural cell that lines capillaries and plays key roles in controlling vessel diameter, maintaining blood-brain barrier integrity, and driving angiogenesis. To study these critical cells, we combine in vivo imaging with advanced genetic, optical, and chemical tools to manipulate pericytes. This integrative approach allows us to uncover their roles in brain physiology and pathophysiology, paving the way for deeper insights into vascular function. Funded by NIH R01 AG062738.
The birth of brain capillaries
As neuronal circuits for sensorimotor function mature postnatally, the vascular networks supplying these circuits also undergo critical development. Using multi-photon imaging during early life stages, our work has uncovered key steps in the formation of these networks, which are vital for ensuring proper blood delivery. However, this intricate process can be disrupted by perinatal complications such as apnea of prematurity and intermittent brain hypoxia. Our ongoing research aims to unravel how vascular networks develop in vivo and to explore the long-term consequences of disruptions in vascular growth during early development.
Pericyte G-protein coupled receptors and modulation of capillary perfusion
Capillary constriction in the brain is a hallmark of neurodegenerative diseases, leading to impaired cerebral blood flow. G-protein coupled receptors (GPCRs), such as thromboxane A2 and endothelin-1 receptors, are powerful mediators of pericyte contraction and play a critical role in this process. Our ongoing research employs CNS pericyte-specific genetic manipulations to uncover how GPCRs regulate capillary blood flow under normal conditions and in models of cerebral small vessel disease. Additionally, we are developing novel mouse models of cerebral hypoperfusion by leveraging chemogenetic tools to precisely control brain capillary perfusion. Funded by NIH R01 AG081840 and R61 NS137365.
Brain Drain: In vivo imaging of capillaries and venules at the gray-white matter interface
The cerebral white matter is highly vulnerable to damage during aging and dementia, yet the mechanisms driving its loss remain poorly understood. To address this, we employ advanced deep multi-photon imaging in live mice to investigate how age-related impairments in venular drainage contribute to the degeneration of cerebral white matter and adjacent gray matter. This research aims to establish a novel experimental framework for exploring the causes of small vessel pathology and evaluating potential therapeutic interventions in mouse models of dementia.
Funded by NIH RF1 AG077731.
