SHIH LAB
About the lab
Our research focuses on the small blood vessels that delivery oxygen and nutrients to the brain. In the adult human brain, an estimated 200-400 miles of vasculature delivers blood to 100 billion neurons. This immensely complex task can go awry during human disease. When we are young, genetic and environmental factors can compromise the normal development of brain vasculature. These changes may affect brain function later in life. As we age, leakage and blockage of small vessels can contribute to Alzheimer’s disease and related dementias.
Our goal is to understand the fundamental mechanisms that control brain vascular function, and to unveil new strategies and therapeutic options for improving cerebrovascular health in brain diseases across the lifespan.
IN VIVO BRAIN VASCULAR IMAGING
Visualizing the plumbing of the brain
To study how blood vessels in the brain grow, degrade, and respond to injury, we use rodent models and advanced imaging approaches (multi-photon microscopy) to study the movement of blood cells in the living brain. To gain access to the brain, we create cranial windows that replace the bone with glass. Then, dyes are introduced to the blood stream label the plasma like "fluorescent angiograms".
Dissecting the control of blood flow in
brain capillaries
A variety of cell types cell types line the walls of cerebral blood vessels. These cells serve different roles in the regulation of brain vascular function. Our lab has heavily studied brain pericytes, a type of mural cell cell lining capillaries, involved in controlling vessel diameter, blood-brain barrier integrity, and angiogenesis. To study pericytes, we couple our in vivo imaging techniques with genetic, optical and chemical-based approaches to modify and manipulate pericytes so that their roles in brain physiology and pathophysiology can be better understood.
The birth of brain capillaries
As neuronal circuitry important for sensory and motor control develop postnatally, so do the vascular networks that supply nutrients. To study how this process is orchestrated, multi-photon imaging can be used in early life stages. This has revealed critical steps in the formation of vascular networks that are essential to blood flow delivery in adulthood. However, these steps may be derailed with perinatal complications, such as apnea of prematurity and intermittent brain hypoxia. Our ongoing work seeks to understand how vascular networks develop in vivo, and the lasting consequences of developmental issues that affect vascular growth.
