The Colton lab has focused on inflammation in the brain, a core response of the immune system, for more than 25 years. Inflammation is the body's major defense mechanism against injury and "invaders" such as bacteria or virus. Our lab studies the innate immune response in the brain and its role in neurodegeneration.
The innate immune response has been viewed as the first line of tissue defense and uses highly pleiotropic cells of hematogenous origin known as macrophages. In the brain, resident macrophages are termed microglia. These cells detect disease-related signals, migrate to injury sites, kill invaders, and orchestrate repair.
That a single cell type can perform these complex functions is amazing. However, years of evolution have hard wired responses into the innate immune system cells. Tissue macrophages contain a complement of membrane and cytosolic receptors that enable a cellular response to a broad range of pathogens including bacteria, virus, parasites, and fungus. Interactions between highly conserved pathogen domains and receptors initiate downstream signaling events that culminate in activation of macrophages.
Genes induced during this process institute a pro-inflammatory phase of macrophage activation that typically results in the expression of acute phase proteins (TNFa, IL1 and IL6), chemokines, proteases and redox proteins that aid in tissue defense. But the "killing" phase of the innate immune response is only half of the story...
Microglia are also involved in repair and reconstruction of the tissue after injury and produce anti-inflammatory factors as well as proteins used in building new tissue. Because of their important role in inflammation, microglia contribute to both acute and chronic neuroinflammatory diseases of the brain and spinal cord. We are particularly interested in understanding how microglia contribute to Alzheimer's disease.
Our lab projects include studying the role of apolipoprotein E in inflammation and why the presence of an APOE4 gene makes Alzheimer's disease worse, particularly in women. We are also using our knowledge on microglia to develop more useful mouse models of AD that will allow us to examine the mechanisms that underlie the disease process and help to find new and better therapeutics. An exciting new mouse model has just been created that shows all aspects of AD pathology with disease progression to tau pathology and neuronal loss. This model is proving to be useful in studies on drug treatments of AD.