What We Do

The CfS for ME/CFS is designed to rapidly adapt to the insights and opportunities that are continuously emerging in the field of ME/CFS research. Accordingly, we are a center without walls—we recruit new investigators nationally and internationally based on their commitment and expertise rather than their institutional affiliation.

Our funding during the first two years of the Collaborative Center Program will be used to mine the rich data and sample sets established with the support of the NIH, the Hutchins Family Foundation, and the Microbe Discovery Project. This work is inspired by discoveries in our laboratory and others pointing to the importance of the microbiome, the virome, and the fungome as determinants of health. We will look for immune responses that may persist long after an infectious agent has either been cleared from the body or become dormant, and for autoantibodies. We will also profile metabolites in plasma and gene expression in white blood cells.

Clinical research studies will connect with the laboratory studies. We will examine the impact of physical activity on the microbiome, the metabolome, and the transcriptome for clues to understanding the basis of persistent fatigue, cognitive dysfunction, and other symptoms after exercise. We will design a mobile app and mine existing datasets for insights into clinical features, comorbidities, and sub-types that could refine laboratory analyses and enhance care.

We are hoping to find additional resources for epigenetic studies that could explain how genes are turned on or off in response to exercise. Clinical trials are not part of our current mandate. However, we are aware of the urgency and need for progress in clinical care. Each of our projects has been prioritized for its potential to lead to solutions for ME/CFS through the development of animal models of ME/CFS or clinical trials of antibiotics, pre- and probiotics, antifungals, antivirals, or immunomodulatory treatments.

Learn more information about each of the three main projects supported by the NIH award below.

Project 1: Microbiology and ME/CFS

The project will explore the role of infection and immunity in ME/CFS. Many ME/CFS patients report a prodrome consistent with infection and/or inflammation. Up to 40% of patients are reported to respond to intravenous infusions of the Toll-like receptor 3 agonist, Ampligen, a double-stranded RNA analogue proposed to inhibit viral replication. Others report responses to antiviral drugs specific for herpesviruses, pre- and probiotics or fecal transplantation, or monoclonal antibodies that deplete B cells. This project will use sequence-based methods for detection and characterization of bacteria, viruses, and fungi, using blood, oral, and fecal samples from ME/CFS cases and controls. We hypothesize that at least some ME/CFS patients have an infectious trigger for their disease, and that failures to implicate infectious agents reflect inadequate sampling and/or inappropriate assays. This project has the potential to lead to the development of animal models based and to identify patients with ME/CFS who may benefit from antiviral, antibiotic, or probiotic interventions.

Project 2: Molecular Signatures for ME/CFS Sub-types

The laboratory project is a comprehensive project to understand the metabolic and transcriptional perturbations that occur in ME/CFS. Transcriptional studies in ME/CFS performed on circulating leukocytes have indicated a combination of immune cell dysfunction and altered metabolic properties, but have generally been performed on limited numbers of individuals using less advanced transcriptional profiling. Published metabolomic studies in ME/CFS have consistently revealed evidence for abnormalities, with evidence for disturbances in lipid metabolism and neurotransmitter-related pathways in particular. We will explore lipid and neurotransmitter metabolism abnormalities, in particular, those involving complex lipids and tryptophan metabolites.

We will then study the peripheral blood mononuclear cell (PBMC) of the same individuals with ME/CFS, seeking any transcriptional patterns. Our approach uses single cell transcriptomic reference data in combination with a published analytical algorithm to measure the proportions of cell subtypes in PBMC from RNA-seq data. This allows a gene expression change in PBMC to be attributed to either a change in cell subtype proportion, or to a genuine alteration in expression of a gene. This allows, for the first time, two distinct but individually interesting biological events to be distinguished – the cell subtype and transcriptional alterations associated with ME/CFS.

Project 3: Clinical Correlates and Diagnostics in ME/CFS

This project will lay the foundation for resolving diagnostic and prognostic uncertainty, distinguishing sub-types, enabling insights into pathogenesis, and facilitating management of illness. We will establish a translational research hub based on the CfS for ME/CFS clinical network. The network will be fully committed to the NINDS Common Data Elements project and to collection of survey data and biological samples needed for rigorous clinical research. We will also work alongside representatives from the ME/CFS community and clinicians to design a mobile app, myME/CFS, to help patients and physicians acquire valuable longitudinal data and personally and clinically manage the illness. Aggregated data from the app may yield insights into triggers that initiate or exacerbate disease, including links between infection and disease in a subset of patients. Finally, we will mine existing databases to identify clinical sub-types that differ in presentation, course, comorbidities, family medical history, or other features. Finally, we will assess the clinical utility of a simple office-based test for autonomic dysfunction, the Lean Test. We will also assess the impact of the Lean Test and an Exercise Tolerance Test on plasma metabolomics and PBMC transcriptomics.

CfS for ME/CFS Publications

ME/CFS and long COVID share similar symptoms and biological abnormalities

Different risk factors distinguish myalgic encephalomyelitis/chronic fatigue syndrome from severe fatigue

Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls

Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

A new clinical challenge: supporting patients coping with the long-term effects of COVID-19

Insights from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome (Komaroff Review)

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (Komaroff Review)

Will COVID-19 Lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS (Komaroff Review)

Can the light of immunometabolism cut through "brain fog"?

Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome

Generating the blood exposome database using a comprehensive text mining and database fusion approach

Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome

 

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