Center participates in the NIH ME/CFS Research Roadmap series

The working group of the National Advisory Neurological Disorders and Stroke Council, part of the National Institutes of Health, recommended the development of research priorities for ME/CFS to help move the field towards translational research and clinical trials. The result led to creation of the ME/CFS Research Roadmap Working Group. The Group, co-led by Drs. Lucinda Bateman and Maureen Hanson, produced a series of eight webinars. A complete description of the webinar series can be found on the ME/CFS Research Roadmap website.

Our Center’s mission is to promote research to identify its cause(s), biomarkers, and pathophysiology in order to lead to prevention and effective treatments. With this focus, several Center investigators presented data to support the development of research priorities for ME/CFS. The talks from our Center are included below.

Maureen Hanson presented “ Immune cell-type approaches to identify mechanisms of ME/CFS” during the Immune System webinar. Her talk starts at 1:38:40.

Jessica Maya presented “Investigations and Consequences of Altered Metabolism in ME/CFS Immune Cells” during the Metabolism webinar. Her talk starts at 58:32.

Maureen Hanson presented “Chronic infection in ME/CFS: non-Herpes viruses” during the Chronic Infections webinar. Her talk starts at 1:01:25.

Ludovic Giloteaux presented “Extracellular vesicles” during the Physiology webinar. His talk starts at 3:15:10.

The NIH ME/CFS Center presents lectures at “Advancing ME/CFS Research: Identifying Targets for Intervention and Learning from Long COVID”

NIH held a hybrid online conference on the NIH campus on December 11-12, 2023.  Center personnel attending in person were  Claire McNally, Annie Gardella, David Iu, Jessica Maya, Tien Luyen (“Louis”) Vu, Katherine Glass, Arnaud Germain, Ludovic Giloteaux, Dawei Li, Andrew Grimson, and Maureen Hanson, as well as collaborator Nicholas Hampilos from Weill Cornell Medicine.

Both days of the conference are available online.

Videocast Day 1

Jessica Maya’s presentation “Investigating T cell populations for immune cell dysfunction in ME/CFS” starts at 3:50:10.

Videocast Day 2

Maureen Hanson’s presentation on “ME/CFS and long COVID: similarities and differences” starts at 1:03:00.

Andrew Grimson’s presentation on “Monocyte dysregulation in ME/CFS” starts at 1:37:35.

Nicholas Hampilos’ presentation on “Effect of Physical Exertion on CNS Oxidative Stress and Metabolism in ME/CFS” starts at 2:56:53.

Center trainees participate in the Symposium For Promoting The Advancement Of Research Knowledge In ME/CFS (SPARK ME)

NIH sponsored an early career researchers workshop on December 10, 2023 attended by Cornell graduate students Claire McNally Annie Gardella, and David Iu, postdoctoral associates Jessica Maya and Tien Luyen (“Louis”) Vu, and Research Associates Katherine Glass, Arnaud Germain and Ludovic Giloteaux.  Drs. Glass and Maya helped organize the meeting.

Verbal presentations:

David Iu: Epigenetic Reprogramming of CD8+ T cell Populations Drives Exhaustion in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Tien Luyen Vu: Single-cell transcriptomics of ME/CFS circulating immune system before and after symptom provocation

Poster presentations:

Anne Gardella: Cell-free RNA signatures of myalgic encephalomyelitis/ chronic fatigue syndrome

Ludovic Giloteaux: Extracellular vesicle protein cargo in ME/CFS cases and controls following maximal exercise

Arnaud Germain: Proteomic adjustments following induction of post-exertional malaise

Claire McNally: Investigating the role of iNOS in endothelial dysfunction in ME/CFS

ME/CFS lecture presented at the Viral Infections and Inflammation Workshop in Rockville, Maryland September 6-7, 2023

In an NIH-sponsored workshop featuring studies of long COVID, acute COVID19, HIV/AIDS, viral encephalitis, Epstein-Barr Virus, Ebola virus, Endogenous retroviruses, Maureen Hanson presented a talk entitled “Viruses, Immune Dysfunction, and ME/CFS

All talks can be accessed through the following website after free registration here or on the Academic Medical Education’s YouTube channel. Maureen Hanson’s talk is included below.

Urine metabolomics shows divergent response to exercise between people with ME/CFS and sedentary controls

Graphical abstract by Katie Glass

We have a new study published today that compares metabolite levels in urine of ME/CFS patients and sedentary controls before and after cardiopulmonary exercise testing (CPET).

Katie Glass is lead author of Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients. The study is available online in the International Journal of Molecular Sciences and full text is open access.

Katie Glass

As shown in the graphical abstract above and explained in the video abstract below, we found a large number of metabolites at increased concentrations in the urine of controls 24 hours after CPET compared to baseline.  However, we did not find significant changes in levels of any metabolites in the urine of ME/CFS patients after CPET.

When we looked at which metabolites were changing differently in ME/CFS patients and controls after exercise, we found the most compounds in the amino acid and lipid metabolic superpathways.

Overall, our data suggests that the metabolisms of sedentary controls undergo major changes that allow them to recover from exertion, while ME/CFS patients fail to make similar adaptive responses. This dysfunctional metabolic excretion could be contributing to exercise intolerance in ME/CFS patients.

Check out the paper to see many more results, including individual compounds that are significantly different between patients and controls and altered correlations between urine and plasma metabolites.

Video abstract by Katie Glass

Fatty Acid Oxidation in ME/CFS Immune Cell Populations

A new publication from the Center on fatty acid oxidation in immune cells has appeared today. Jessica Maya is the lead author of Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome published in the International Journal of Molecular Sciences.

As discussed in the paper, there is more evidence for abnormal immunometabolism in ME/CFS. Maya utilized her expertise in flow cytometry and Seahorse flux analysis to demonstrate this dysfunction. She isolated natural killer (NK), helper T (CD4), and cytotoxic T (CD8) cell populations from both healthy donors and people with ME/CFS. These immune cell populations were studied in their circulating state and after stimulation. The stimulation process aims to mimic an immune response. Maya’s findings showed that all three of the cell types have an increased use of fats to power their activities when compared to healthy donors. Her results show that ME/CFS immune cells have a greater reliance on fats for energy when they are stimulated. Overall, these findings support the presence of an altered metabolic state in certain immune cells in individuals with ME/CFS.

Maya outlines these findings in her graphical and video abstracts inserted below.

Graphical abstract by Jessica Maya
Video abstract by Jessica Maya

A commentary by Andrew Grimson about the single-cell RNA-seq preprint from his lab

When we started this project, our goal was to ask which components of the immune system are most altered in ME/CFS (and which are not). If we could answer this question, we hoped that it would give us a clear path towards understanding some of the molecular underpinnings of ME/CFS, which is likely to be an essential step towards therapies. We used a technique called single-cell RNA sequencing to answer this question, an approach that looks at the genes expressed in thousands of individual cells from each ME/CFS individual (and control). When we look at the data (which in aggregate contains about 0.5 million immune cells found in peripheral blood, sampled from 30 ME/CFS individuals and 28 controls), the strongest signal of dysregulation is found in classical monocytes, a type of innate immune cell with diverse roles. There are three fundamental observations we can make about monocytes in ME/CFS. First, within individuals with ME/CFS, the proportion of monocytes that are dysregulated is variable, with a mixture of relatively normal cells and those that are altered. Second, comparing between individuals, the proportion of altered monocytes is also variable, with individuals with a higher fraction of altered monocytes tending to have more serious cases of ME/CFS. Third, by looking at the genes mis-expressed in altered monocytes, we can find patterns that suggest what might be different about the biology of the altered monocytes. In essence, what we see is that monocytes in individuals with ME/CFS appear to be triggered to migrate to tissues, where they become macrophages. This migration and differentiation pathway is a normal function of monocytes – we think the pathway is more active in ME/CFS, and this increased activity could contribute to many of the symptoms of ME/CFS. This work sets up lots of questions that motivate our work now – where are the monocytes going in ME/CFS individuals, what is causing them to be dysregulated, and ultimately, can we reverse this dysregulation?
Continue reading “A commentary by Andrew Grimson about the single-cell RNA-seq preprint from his lab”

CDC SEC call on Immune Dysfunction in ME/CFS

On September 23, 2020, a CDC ME/CFS Stakeholder Engagement and Communication (SEC) call took place, featuring a presentation by Dr. Maureen Hanson, ENID Center Director, on “Immune Dysfunction in ME/CFS”. Dr. Elizabeth Unger, Branch Chief of CDC’s Chronic Viral Diseases Branch, provided CDC programmatic updates. The SEC call transcript, audio, and presentation slides are now available on the CDC’s website. Direct links to specific content, including Hanson’s slideshow presentation, are below.

Listen to the audio recording.

Read the transcript.

View Dr. Hanson’s presentation.

Maureen Hanson presents at Cornell COVID-19 Summit 2020

On November 4-5, 2020, Cornell University and Weill Cornell Medicine held a COVID-19 Summit to exchange information about research into the disease ongoing at both institutions. Dr. Maureen Hanson presented a “flash” talk with three slides to introduce Cornell COVID-19 researchers to the similarity between long-haul COVID-19 and ME/CFS. Content from Hanson’s talk is below.

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