Glia cells: Glia are cells in the brain that were long thought to be “helpers” that support neurons to perform their functions. Freeman has shown that the most predominant and least-studied glial cell, the star-shaped astrocyte, is essential to the brain’s signaling network and allows for many complex behavioral outputs. His research has shown that neuromodulators, a messenger that regulates a diverse group of neurons, function not only through neurons, but signal through astrocytes as well. Currently, his research explores how neurons and glia cells communicate with one another so the nervous system runs smoothly and how their dysfunction can result in neurological disease.
Axon degeneration: Axons, slender nerve fibers, must remain intact to function, and, in cases of injury or disease, they break. His research team exploited the unique set of genetic tools available in fruit flies to label specific subsets of neurons in the intact animal, cut axons to induce degeneration, and then systematically broke each gene in the fly genome to determine which were required to promote axon destruction. They discovered that when dSarm/Sarm1 was deleted it completely blocked axon degeneration, and went on to show the same was true in mice and human cell lines. Remarkably, Freeman and his colleagues have recently found that blocking the Sarm1 pathway alleviates nearly all pathological effects of traumatic brain injury in mice. Other labs have implicated Sarm1 signaling in peripheral neuropathy. These findings indicate that if researchers can find a way to block the genes that drive degeneration after injury—something Freeman’s lab is currently pursuing—there’s an opportunity to save the nervous system from degeneration in many cases of injury or neurodegenerative disease.