Fellowship will fund research into myelin sheath repair in MS
UMass PhD student to use award to study role of microglia in remyelination
A PhD student at the UMass Chan Medical School will use funding from a newly awarded fellowship to advance his research into the mechanisms used by cells to repair myelin, the protective sheath around nerve cells that’s damaged in multiple sclerosis (MS) and other demyelinating conditions.
The ongoing research by new fellow Jacob Stillman may open new therapeutic avenues to boost myelin repair, or remyelination, which may help to slow or even reverse the progression of these disorders.
Stillman is the recipient of a Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship, which is given to promising doctoral candidates, according to a university press release. The award will provide up to five years of support to Stillman for his dissertation research.
The fellowship funding is from the National Institutes of Health’s National Institute of Neurological Disorders and Stroke.
Stillman is pursuing his doctoral studies in the lab of Dorothy Schafer, PhD, an associate professor of neurobiology at the Massachusetts school, who says that her student is already advancing the field of myelin sheath repair.
PhD candidate’s work already shows promise in myelin sheath repair
MS is marked by inflammatory damage and loss of the myelin sheath — called demyelination — in the brain and spinal cord. When myelin is damaged, nerve cells cannot send electrical signals as effectively, which causes neurological problems that give rise to MS symptoms.
As myelin is damaged, the resulting debris must be cleared to make room for new myelin. This cleanup process is usually done by microglia, the resident immune cells in the brain.
However, remyelination is not very efficient in MS due to ongoing inflammation. Further, it tends to worsen with age. Stillman’s work has shown that microglia may actually prevent remyelination from occurring.
“During demyelination, brain resident innate immune cells called microglia eat myelin debris and dying cells to clear lesions for remyelination,” Stillman said.
“As people get older, or the disease switches into a progressive phase, demyelinated lesions aren’t able to remyelinate efficiently. We found that as microglia eat myelin debris, this can trigger antiviral signaling pathways and harm the ability of the central nervous system to remyelinate,” he added.
Microglia in the brain eat cell debris, which normally reduces inflammation and promotes regeneration, but Jacob’s work shows for the first time that overeating cell debris in the diseased brain can cause the opposite.
In his research, Stillman is focusing on a family of protein receptors called toll-like receptors (TLRs), which play a critical role in activating a large variety of immune cells, including microglia.
Specifically, he will be investigating TLRs in endosomes, or sac-like structures inside cells used by some viruses for cellular entry and transport.
According to Schafer, this work “offers a completely new target for therapeutic intervention.”
“Microglia in the brain eat cell debris, which normally reduces inflammation and promotes regeneration, but Jacob’s work shows for the first time that overeating cell debris in the diseased brain can cause the opposite,” Schafer said.
Stillman is working to become a specialist in brain and spinal cord immunology and hopes to establish himself as a professor in the future. The student from New York says his interest in science started at “a very young age.”
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