Dr. Glass’ project focuses on how inflammation in the body reshapes brain immune responses and contributes to Alzheimer’s disease (AD). Although genetic studies have implicated microglia and other brain-resident immune cells in AD, increasing evidence suggests that signals originating outside the brain—including cytokines, microbial products, and immune mediators—can have lasting effects on brain immunity.
Prior work from this lab demonstrated that peripheral inflammatory stimuli, such as lipopolysaccharide (LPS), rapidly activate endothelial cells and Border-associated macrophages (BAMs) at the brain’s boundaries. These cells then transmit signals to microglia and other brain cells, leading to both immediate inflammatory responses and longer-term functional changes, a process often referred to as innate immune memory.
The team will determine whether endothelial cells and BAMs are required to sense peripheral LPS by selectively deleting or restoring key receptors and measuring downstream changes in inflammatory and spatial gene expression. They will define how LPS induces persistent epigenetic changes in microglia that may contribute to long-term immune reprogramming. Finally, they will compare how different immune stimuli, such as tuberculosis (BCG) vaccination, which has been shown to reduce AD risk, and LPS exposure, induce distinct long-lasting transcriptional and epigenetic states in microglia to understand whether aspects of immune training could be therapeutically harnessed.
In collaboration with partners of the Neuroimmune Consortium, the Glass lab will integrate epigenetic, spatial, and functional datasets to define how peripheral inflammatory signals reshape the brain’s immune landscape and contribute to Alzheimer’s vulnerability.
