Brain Vascular Heterogeneity

In the vertebrate brain, vascular endothelial cells exhibit heterogeneous structural and functional properties that are critical to mirror the brain’s diverse functions.  Two striking examples of this heterogeneity are the vECs that form the semi-permeable blood-brain barrier (BBB) and those that develop highly permeable fenestral pores (fenestrae). We are very interested in understanding how these heterogeneous brain vascular networks are generated during neural development.  Our current focus is to define the cellular and molecular basis of fenestrated brain vascular development using the choroid plexus as a model system.

Blood-CSF Barrier

The blood-brain barrier (BBB) and blood-cerebrospinal fluid (blood-CSF) barrier are important CNS barriers that protect the brain from potentially harmful toxins, pathogens, and/or substances. The blood-CSF barrier is formed by tight junctions between epithelial cells in the choroid plexus, a small organ in the brain that serves to produce cerebrospinal fluid and remove metabolic wastes from the brain. We are interested in understanding how choroid plexus epithelial cells are assembled to establish the unique barrier integrity and properties, thereby regulating the CNS microenvironment and homeostasis. Developmental understanding of the blood-CSF barrier genesis will help to repair its barrier impairment in structure and function.

CNS Vascular Morphogenesis

In the central nervous system (CNS), blood and lymphatic vasculature develops in very distinct and unique patterns to support diverse CNS function. The CNS parenchyma is highly vascularized, but devoid of lymphatic vasculature. In contrast, both blood and lymphatic vessels are well formed in the meninges, the protective membranes that enclose the brain and spinal cord. Meningeal blood and lymphatic vasculature mediates efficient clearance of CNS metabolic wastes and fluid, as well as neural immune surveillance, thereby maintaining CNS homeostasis and health. We are trying to understand the developmental programs that lead to specific patterning of CNS blood and lymphatic vasculature, specifically focusing on the meninges. A deeper understanding of the mechanisms underlying meningeal angiogenesis and lymphangiogenesis will help to maintain brain health, immunity, and homeostasis.