Development & Maintenance of the BBB

What are the cellular and molecular mechanisms that govern development and maintenance of the BBB?

Lab research photo retina

Vasculature of the developing retina

We are interested in identifying key signaling pathways that regulate formation of the BBB in order to repair BBB function in CNS diseases in which the barrier breaks down.

We have found that the Wnt/beta-catenin pathway plays an important role in regulating both CNS angiogenesis and some properties of the barrier. We have identified a novel inhibitor of this pathway named Apcdd1 that is expressed in CNS endothelial cells when they acquire their barrier properties during development. We are currently investigating the roles of Apcdd1 in CNS angiogenesis and blood-brain barrier development.

We are also interested in understanding how tight junctions between endothelial cells in the CNS develop and mature during BBB formation. We have developed proteomic discovery platforms for: a) identifying novel junctional proteins important for barrier development and function; and b) potential structural modifications of tight junction proteins that underlie CNS diseases exhibiting reduced barrier function.

Related publications

Current projects

Cellular and molecular mechanisms of blood-retina barrier formation and maintenance.

In the Agalliu laboratory, Rishi primarily focuses on the development and maintenance of the blood-retina barrier. In one project, Rishi studies the role of canonical Wnt signaling, specifically the canonical Wnt inhibitor Apcdd1, in these processes. Although canonical Wnt signaling has been shown to regulate barriergenesis in retinal vessels, the precise downstream cellular and molecular mechanisms by which that is achieved is unclear. This study aims to elucidate those unanswered questions, with the ultimate goal of finding novel therapeutic approaches to treat neurovascular disorders.

A second project examines how retinal neuronal activity affects the blood-retina barrier formation. This is one area of neurovascular coupling that has not been explored previously. These studies have the potential to uncover new mechanistic insights into the interdependency of neural and vascular development.