MGH Research Scholars Program
The MGH Research Scholars Program was established to support early career researchers with innovative yet unproven ideas that have the potential to transform the future of medicine. Funded 100% through philanthropy, this program gives researchers the freedom and flexibility they need to follow the science wherever it leads. History has shown that brilliant scientists who are given free rein to explore new frontiers make the greatest, often unexpected, advances.
Misreading the Epigenome: Consequences for Immunological Diseases
The immune system acts to defend against harmful invaders without damaging healthy cells. When there is an imbalanced activity of the immune system, however, immune disorders such as autoimmunity or inflammation can result.
Immune disorders have increased dramatically in the past 60 years and are therefore not readily explained by host genetics. Instead, these trends implicate dynamic environmental or epigenetic factors in disease.
Epigenetics enable cells to alter gene expression without modifying the genetic code, and therefore represent potent mechanisms by which cells can respond, transiently or stably, to environmental cues. Dysregulation of epigenetics is a central event in cancer, yet virtually nothing is known how altered epigenetics contributes to immune disorders.
With this proposal, we will investigate the contribution of epigenetics to two prevalent immune disorders: inflammatory bowel disease (IBD) and multiple sclerosis (MS) by focusing on an epigenetic enzyme called SP140. This enzyme has mutations within it that are associated with both IBD and MS.
We recently found that SP140 mutations have profound consequences on the identity and function of immune cells. These studies could change our current understanding of IBD and MS by recognizing altered epigenetics as a driver of immune disease, and also pave the way for new precision-based therapies.