Attributions

High Throughput Discovery of Blood-Brain Barrier Functional Components

Ethan Lippmann, PhD Vanderbilt University

Co-Principal Investigators

Laura Dugan, MD Vanderbilt University Medical Center

Summary

In patients with Alzheimer's disease (AD) and dementia, the blood vessels of the brain become leaky, which worsens symptoms like memory loss. We are trying to identify why these blood vessels become leaky. If we understand the cause of this leakage, we can potentially target it with new drugs to improve patient outcomes. 

Project Details

The goal of our project is to better understand how the blood vessels in the brain form the blood-brain barrier (BBB), which normally protects the brain from toxic substances but becomes leaky in diseases like Alzheimer’s and dementia. In the first portion of the project, we are using a cell line that mimics BBB function and systematically removing every human gene to test their effects on barrier properties. The most promising “hits” from this screen are to be re-tested in human BBB cells that we produce in the lab. Finally, we are confirming that these genes are lost in mice whose BBB has been disrupted, thus demonstrating their functional importance.

Our proposal is the first to merge genome editing technology with explorations of BBB function. Furthermore, we are able to generate an unlimited quantity of human BBB using induced pluripotent stem cells (iPSC, a stem cells technology that grows cells from tissue samples from living adults). Together, these techniques will allow us to unravel the mysteries of BBB function to understand why the blood vessels in the brain start to leak and how this contributes to serious brain diseases. Once our study is complete, we will use this information to hunt for new drugs that manipulate these new targets and prevent BBB leakiness. These drugs may provide new treatment options for Alzheimer’s and dementia.