Glial cells constitute approximately half of the cells in the human brain. As the largest population of glial cells, astrocytes are crucial for the survival and function of neurons. Defects in astrocyte generation are associated with severe neurological disorders including gliomas, the most common primary brain tumor. The rapid growth of the rodent brain during the early postnatal period is accompanied by a 4-fold increase in blood vessel density, in parallel with a 6- to 8-fold increase in glial cell population, which predominantly contains astrocytes.
So far, little is known about the cellular and molecular mechanisms of astrocyte generation in the postnatal brain. In the short term, we will study the molecular mechanisms that are responsible for the local generation of astrocytes in the postnatal brain.
Formation of Gliovascular Interface
Astrocytic endfeet and brain vasculature form an intricate structure called the gliovascular interface, which is critical for the transport of glucose from the blood to neurons, the regulation of cerebral blood flow, and the maintenance of the blood-brain barrier. Detachment of astrocytic endfeet from the vascular membrane is responsible for brain edema and results in neurodegeneration. Thus, the ability to restore its function after stroke is of the utmost importance for improving functional brain recovery in patients.
Unfortunately, how the gliovascular interface forms and develops is unclear. We will study the cellular and molecular mechanisms for interactions between brain vasculature and astrocytes with genetic manipulation and time-lapse slice or in vivo imaging.
Pericyte Subtypes and Their Interactions with Neurons/Astrocytes
Although pericytes are located along vessels in both the central nervous system and other organs, only the vasculature in the central nervous system is covered by astrocytic endfeet. It remains unclear whether there are subtypes of pericytes in blood vessels, and if so, what their functions are in the brain, and how different subtypes of pericytes interact with glial cells or neurons in the brain.
To answer these questions, we will introduce techniques including electrophysiology and in vivo imaging into the study of brain pericytes. The goal is to isolate pericytes from arteriole, pre-capillary, capillary, post-capillary and venule to characterize the molecular and cellular profile of pericytes from different locations.
Development of New Tools
We believe that new techniques are critical for opening a new field in biomedical research. We are interested in developing new tools in the study of brain development, brain vasculature, and neurovascular/gliovascular interaction in live animals.