Investigators, Dr. Susan Bellis, PhD and Dr. Laurie Harrington, PhD were selected for funding by MS Research Accleration Fund for 2017-2018 cycle. The project, ST6Gal-I Regulation of CNS Inflammation, aims to shed new light on the role of glycans in influencing autoimmunity and to provide novel targets for new MS therapies.
Multiple Sclerosis (MS), a debilitating autoimmune inflammatory disease of the central nervous system (CNS), involves the infiltration of the CNS by immune cells, including T cells and macrophages. While an extensive amount of research has been devoted to understanding the events that drive MS, the role of cell surface sugars (“glycans”) has been largely ignored. Most of the proteins on the cell surface responsible for regulating immune cell behavior are decorated with glycans. These glycans can change the shape and function of proteins, which can subsequently adjust the actions of the cells. Studies from involved UAB researchers have shown that a specific glycan called sialic acid alters the function of important proteins that control cell survival. The protein that adds this sialic acid, ST6Gal-I, has been associated with MS in Genome Wide Association Studies.
The central hypothesis of this study is that ST6Gal-I modifies cell surface proteins on T cells and macrophages, prolonging their survival. In turn, the persistence of these immune cells causes greater CNS damage, exacerbating MS. To decipher the role of ST6Gal-I in different immune cell populations during MS, the Harrington and Bellis laboratories will use the animal model of this disease in which the levels of ST6Gal-1 are tightly controlled. From these studies, they will determine if increased levels of ST6Gal-1 on macrophages and T cells enhances disease severity, as well as if loss of ST6Gal-1 in these cells reduces and/or inhibits disease.
The UAB Multiple Sclerosis Center awards funding for up to 4 research projects per year to exceptional UAB scientists in support of novel research in the field of MS. These awards, made possible through generous philanthropic giving, advance promising MS research and undergird high-risk/high-reward projects with the potential to discover new treatments with disease-modifying impact. Awards will ultimately create preliminary data that will support more permanent funding through Federal agencies and/or non-profit entities. The second funding cycle began in February 2017.