The Colton Lab has focused on the function of the immune response in the initiation and progression of brain disease. It is now known that the brain is not “immune privileged”, and Colton’s early studies on microglia (the brain macrophage) have been seminal to the field. By using multiple experimental approaches, Dr. Colton now clearly demonstrates that the brain’s immune activity both depends upon and alters the supply of available metabolites within the enclosed confines of the brain’s unique compartments. This is critical to a prolonged disease state such as Alzheimer’s disease (AD) that initiates long-lasting abnormal cellular and tissue metabolic changes within the brain’s enclosed environment. As a result, neurons, microglia and astrocytes are required to adapt to damage or disruption, resulting in changed brain functional outcomes. Perhaps similarly to harboring a parasite, the brain learns to live with the chronic immune disruption that is AD. However, this adaptation is costly to overall brain metabolism and to the maintenance of normal functions.

To understand the impact of brain disease, Dr. Colton has taken an integrated approach, incorporating regional brain pathology with cellular changes using multiple techniques. These range from brain pathology to cellular microscopy to gene and protein analyses. Colton’s primary experimental question currently involves understanding how the AD disease process impacts the brain’s environment by altering metabolism of neurons. Her work has now discovered a novel and critical mitochondrial protein that is disrupted in AD neurons. Radical S-Adenosyl domain 1 (RSAD1) is highly overexpressed in human AD and alters methionine usage in the brain.

Currently, the Colton lab has generated RSAD1 negative and RSAD overexpressing mouse strains, thus providing critical tools to discover the impact on RSAD1 on neuronal and mitochondrial metabolism in the presence of amyloid and phospho tau.