# Probing the Pathophysiology of ME/CFS through Proteomics and Metabolomics

> **NIH NIH U54** · CORNELL UNIVERSITY · 2020 · $387,435

## Abstract

PROJECT SUMMARY: CLINICAL PROJECT 2: PROBING THE PATHOPHYSIOLOGY OF ME/CFS
The underlying reason for the profound fatigue, pain, cognitive difficulties, and the peculiar response to
physical effort of ME/CFS patients, is not understood. One reason that many ME/CFS patients are unable to
work is that their maximal ability to produce energy, measured by cardiopulmonary exercise testing (CPET), is
extremely low. For many ME/CFS patients an increase in physical or mental activity results in an increase in
symptoms termed post-exertional malaise. Prior work by Cornell Center investigators found that most
ME/CFS patients who undergo CPET cannot reproduce, a day later, one or more objective measures such as
oxygen consumption at maximal threshold intensities, and/or exhibit abnormalities in blood pressure and/or
heart rate response. The cause of post-exertional malaise, like the cause of ME/CFS, is not understood,
although it is one of the most debilitating symptoms of ME/CFS sufferers.
 Our central hypothesis is that the study of postexertional malaise provides an exciting opportunity to
obtain new insights into the etiology of ME/CFS. We will obtain samples from patients at several different time
points, prior to an exercise challenge, when they are experiencing their usual levels of symptoms, and at a time
of heightened symptoms, post exercise, enabling deeper insight into abnormal biological functioning
associated with the disease. By analyzing, in conjunction with physiological data, metabolites, circulating
inflammatory molecules, and extracellular vesicle (EV) cargo in blood samples from before and after
exercise sessions, we aim to uncover markers and mechanisms of post-exertional malaise in ME/CFS. Our
broad survey of possible molecular responses to exercise will include inflammatory proteins and immunogenic
mitochondrial DNA (mtDNA) fragments, targeted and untargeted metabolomics of blood serum, and a detailed
proteomic and metabolomic characterization of EVs. EVs are released into the circulation during exercise and
could therefore contain biomarkers or contain cargo that plays an active role in mediating the abnormal
response to physical activity in ME/CFS. EVs cargo includes signaling proteins, lipids, hormones, and RNAs
that can influence the growth, metabolic activity, and gene expression in target cells with which they fuse.
 We expect that the metabolomic analyses of serum and EVs have particularly high potential to detect
ME/CFS-specific changes in the response to exercise, because the metabolome integrates downstream
effects from almost any physiological pathway. Therefore, in addition to conventional targeted metabolomics,
we will introduce untargeted metabolomic analyses as a powerful approach toward discovery of new or
unexpected ME/CFS-associated changes in primary metabolism or the production of signaling molecules such
as hormones, prostaglandins, or neurotransmitters. As a primary outcome of this study, we expect to provide
com...

## Key facts

- **NIH application ID:** 10003412
- **Project number:** 5U54NS105541-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** MAUREEN REBECCA HANSON
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,435
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003412

## Citation

> US National Institutes of Health, RePORTER application 10003412, Probing the Pathophysiology of ME/CFS through Proteomics and Metabolomics (5U54NS105541-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10003412. Licensed CC0.

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