2017 Awardees
Investigators Susan Bellis, PhD, and Laurie Harrington, PhD, were selected for funding by the MS Research Acceleration Fund for the 2017-2018 cycle. Their 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) involves the infiltration of the central nervous system (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 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 an 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.
2016 Awardees
Two Faculty Projects Selected for Funding through the Multiple Sclerosis Center Research Acceleration Fund
Casey Weaver, MD and Hongwei Qin, PhD were selected to receive 2016-2017 funding for research projects identifying new therapeutic targets for the treatment of MS. Dr. Qin's project will examine the function of protein kinaseCK2 in CD4+ T cells and autoimmune disease, while Dr. Weaver's project will focus on novel therapeutics to expand Interleukin-10 producing T cells in the treatment of Multiple Sclerosis.
Dr. Qin’s research aims to establish a novel regulatory role for CK2 in Th17 and Treg cell differentiation during EAE, and will provide preclinical evidence to establish CK2 as a potential new target for treatment of MS, particularly in patients with Th17 cell-dominated primary or secondary progressive MS. MS, an autoimmune disease of the brain and spinal cord that affects a growing percentage of the US population, is the leading cause of neurological disabilities in young adults. Although many therapies are available for MS, they are only partially effective, and none prevent progression of disease. The goal of the proposed studies is to elucidate the molecular mechanisms governing the differentiation of Th17 and Treg cells in the context of Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS, which will lead to target key signals that drive inflammation in MS/EAE. Results from these studies will identify new neuro-protective therapeutic targets for the treatment of MS patients.
Dr. Weaver’s research will perform pre-clinical studies in an MS model of two novel antibodies that act to differentially accelerate the expansion of two distinct populations of IL-10–producing T cells. As humanized versions of these antibodies are already being developed in clinical trials for other indications, these studies will test the potential for re-purposing these antibodies for therapeutic use in MS. Findings from these studies should provide new insights into mechanisms that restrain CNS inflammation in MS, and will allow for definitive analyses of the therapeutic potential of expanding IL-10-producing T cells as a new therapeutic approach in inflammatory disorders, including MS.
The UAB Multiple Sclerosis Center awards funding for up to four 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.