Immune Dsyregulation in Classical Monocytes and Platelets
The project is based on discoveries our Center made previously, in which we identified classical monocytes, a component of the innate immune system, as the circulating immune cells that show that strongest dysregulation in gene expression in ME/CFS. Because post-exertional malaise (PEM) is a hallmark symptom of ME/CFS, we also looked for changes in gene expression across the immune system that might correlate with PEM; this approach revealed that PEM results in a distinctive change in platelets when we compared their transcriptomes before and after a strenuous exercise challenge. Thus, going forward, our major goals are to comprehensively investigate monocyte and platelet abnormalities in ME/CFS.
To examine monocytes in ME/CFS, we will take two complementary approaches. First, we will use multiomic approaches to comprehensively determine the gene regulatory changes in monocytes in ME/CFS. One possible result from these experiments will be the identification of the key drivers of monocyte dysregulation in ME/CFS. Second, we will perform assays to test whether ME/CFS results in alterations in the ability of monocytes to migrate and differentiate into macrophages, a critical function of monocytes. These assays are motivated by our current data, which suggests that monocytes in ME/CFS are aberrantly primed to enter tissues, which is a normal function of monocytes but may be inappropriately active in ME/CFS. The project led by Dr. Cosgrove will examine this possibility by directly investigating macrophages in muscle, and we will work together to examine links between monocyte alterations in the circulation and the possible consequences in tissue.
We will also work with Dr. Hanson to ask whether there are alterations to the platelet-derived extracellular vesicles in ME/CFS, complementing our analysis of platelets themselves.
The project will be led by Dr. Andrew Grimson, an Associate Professor at Cornell Univ. in collaboration with Dr. Dawei Li, an Associate Professor at Florida Atlantic Univ. Dr. Grimson’s lab will use a combination of genomic and functional assays to investigate components of the immune system in ME/CFS, working closely with Dr. Li, a computational biologist. The genomics assays will be performed in partnership with Dr. Grenier, who leads our Research Core component of the Center.