BLOOD BRAIN BARRIER

Evidence of blood-brain barrier (BBB) disruption has been implicated in psychosis but is not well understood. The BBB maintains neural homeostasis by regulating cellular and molecular trafficking between the bloodstream and brain parenchyma. Brain microvascular endothelial cells (BMECs) are an integral component of the BBB. They line blood vessels, forming a monolayer that intereacts with neurons, microglia, pericytes, astrocytes, and the extracellular matrix to make up the neurovascular unit.  We utilize patient-specific BMECs, generated from induced pluripotent stem cells (iPSCs), to uncover potential BMEC deficits and to understand the etiopathology of BBB disruption in psychosis.

Paracellular proteins, transporters, and transcellular proteins in BMECs regulate molecular and cellular trafficking between the bloodstream and the brain parenchyma.
Our lab is interested in specific proteins expressed in BMEC tight junctions, including: 
ML27 CLN5 BMEC-ABx.jpg

Claudin-5 (CLDN5)

CLDN5 is an integral component of the BBB and one of many genes deleted in 22q11 deletion syndrome, which increases the risk of vascular abnormalities and schizophrenia. 
ML27 ZO1 BMEC-ABx.jpg

Tight Junction Protein-1 (TJP1)

One of the zonula occludens family members, TJP1 maintains intercellular transduction and cell-to-cell adhesion that limit paracellular trafficking.
OCLN BMEC+ABx.jpg

Occludin (OCLN)

OCLN plays a regulatory role in paracellular transport and interacts with CLDN and TJP proteins to form the tight junction complex.

Current brain microvascular endothelial cells derivation technique provides an efficient way to obtain high-throughput population of purified iPSC-derived BMECs that express relevant tight junction proteins.
BBB.png
Below: Differentiation scheme of human induced pluripotent stem cells (hiPSCs) to BMECs.
hiPSC-derived BMECs scheme.png
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Peripheral & Neural Inflammation