RESEARCH PROGRAM 2

miR-23b’s role in repairing damaged endothelium

The blood-brain barrier (BBB) plays a critical role in safeguarding the homeostasis of the brain’s microenvironment. The barrier is formed by brain endothelial cells (BECs), which are sealed by specialized tight junctions (TJs) and exhibit minimal caveolar-mediated transport (transcytosis), thus preventing the passage of hydrophilic molecules between blood and brain. We recently made the following advances: 1) developed a safe and efficient reprogramming strategy using RNA modulation of cells and 2) performed a novel anti-microRNA (miR) screen in BECs and showed that anti-miR-23b significantly enhances BEC function by enhancing both expression of TJ proteins and formation of a paracellular endothelial barrier. We’re in the process of optimizing protocols to successfully differentiate iPSCs into BECs with mature BBB properties, by taking advantage of the unique properties of anti-miR-23b alone or in the combination with other RNAs. We are exploring the mechanisms by which miR-23b regulates angiogenic and barrier properties of BECs in vitro and will test the ability of anti-miR-23b to prevent or repair the injured BBB in models for neurological disorders (stroke and Alzheimer’s disease), by using a novel gene therapy approach.

miR-128 degrades full-length L1 RNA