My laboratory is investigating three fundamental issues in the biology of the mammalian blood-brain barrier (BBB): 1) the mechanisms governing development and maintenance of the barrier; 2) how structural components of the BBB are affected in diseases of the brain and spinal cord where barrier function is impaired; and 3) the role of Wnt/beta-catenin signaling in repairing the damaged BBB in CNS diseases.
Endothelial cells that line the blood vessels of the mammalian central nervous system (CNS) form a unique, tight barrier that maintains the homeostasis necessary for neuronal and glial function, and protects the CNS from pathological agents and immune cell invasion. Barrier properties of CNS endothelial cells (ECs) are mediated by three distinct cell biological mechanisms: a) extremely tight junctions that prevent diffusion of small molecules between endothelial cells (paracellular pathway); b) very few endocytotic vesicles (caveolae) that transcytose slowly and thereby reduce transport of large molecules across the brain endothelium (transcellular pathway); and c) transporters that shuttle only selected molecules between the blood and the brain (Figure 1). This barrier breaks down during CNS insults such as stroke, or in CNS autoimmune disorders such as multiple sclerosis (MS)…. Continue Reading →