Research and Funding
Join our research! We want your blood.
Are you a person with ME/CFS, Long COVID or a healthy control? If yes, and if you can come to our lab at UMass Chan Medical School, Worcester, MA, you can join in our studies.
Selin Lab's novel research findings
- Selin and Gil's research findings show clear similarities in the dysregulation of the immune system in three neuroinflammatory diseases: ME/CFS, Long COVID and multiple sclerosis.
- They show these three diseases have unique findings in patients' blood that do not present in healthy people.
- The unique abnormal findings are:
- An increase in the usually rare CD4+/CD8+ (double positive) T-cells
- Increased CD4:CD8 T-cell ratio
- Evidence of CD8 T-cell exhaustion, which leads to poor control of persistent viruses, like EBV, CMV, VZV and HHV6
- An inappropriate immune response to EBV. And, in the case of ME/CFS and Long COVID, an inappropriate immune response to additional persistent viruses as well.
Funding
To date, Dr. Selin has received 12 NIH grant awards, totaling $20 million funded to UMass Chan. Five of those grant awards were part of large highly-prestigious collaborative research projects, which altogether brought $78 million to UMass Chan.
Selin Lab's most recent funders
The Selin Lab thanks its many private donors, from the small donations to the large ones. They all help. If you wish to donate, see here:
In addition to our private donors, our most recent funders are listed below.
Patient-Led Research Collaborative – collaborative research project with HiFiBiO Therapeutics and the Selin Lab (2024).
"Immune repertoire profiling of Long COVID and ME/CFS patients” – Dr. Roshan Kumar, HiFiBiO Therapeutics; and Dr. Liisa Selin and Dr. Anna Gil, University of Massachusetts Chan Medical School. "Multiple lines of evidence point to underlying immune abnormalities in patients with infection-associated chronic illnesses such as Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, how these abnormalities relate to disease symptoms and mechanisms is unclear. In some instances, autoimmunity may underlie chronic illness, while in other cases viral reactivation or persistence may be the primary culprit, and the two may interact so that initial antiviral responses elicit prolonged autoimmune reactions. Defining the targets recognized by immune responses is critical for identification of patient subgroups with distinct underlying disease mechanisms and will enable precision treatment with immunomodulatory or antiviral therapy. In this project, novel single-cell profiling technologies will be applied through the DIS® platform to characterize immune repertoires and identify targets of B and T cell responses in ME/CFS and Long COVID patients. By identifying autoantigens and viral targets of these immune responses, there will be insight into underlying disease mechanisms defining patient subgroups that can be translated into diagnostic biomarkers and therapeutic interventions.”
Patient-Led Research Collaborative (2023)
“Altered T cell responses in Long COVID (PASC) and ME/CFS” – Dr. Liisa Selin and Dr. Anna Gil, University of Massachusetts Chan Medical School. "Based on earlier research, this project hypothesizes that the common theme in Long COVID and ME/CFS is an aberrant response to an immunological trigger like infection that results in a permanently dysregulated immune system as a result of CD8 T cell exhaustion. This project will do a deep dive into the T cells of Long COVID and ME/CFS patients, looking for exhausted and activated subsets, and will additionally look at reactivated herpesviruses in relation to these findings."
National Institutes of Health NIAID (2021)
The National Institutes of Health (NIH) announced a grant awarded to the Selin Lab for their work on ME/CFS. The RO1 grant (AI159314) of $2.5 million is administered by NIH's National Institute of Allergy and Infectious Diseases (NIAID). The grant, titled “Altered T cell Responses in ME/CFS” allows the researchers to examine the role of aberrant T cell responses in the immunopathogenesis of ME/CFS patients. Link to MassME press release on this grant.
NIH ROI (AI159314), Written by Anna Gil and Liisa Selin: "ALTERED T CELL RESPONSES IN ME/CFS." Narrative: This proposal will examine ME/CFS from the perspective that an aberrant response to an immunological trigger like infection results in a dysregulated immune system that is partially immunosuppressed due to CD8 T cell exhaustion. These studies will identify potential biomarkers and mechanisms driving the immunopathogenesis of ME/CFS leading to future therapies. Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder affecting numerous organ systems and biological processes. Published data seems to suggest that ME/CFS may be preceded by infection, and the chronic manifestation of illness may represent an altered host response to infection, or an inability to resolve inflammation. Previous studies focused on perturbation in cytokines and metabolism have also shown that CD8 T responses are decreased in ME/CFS. In preliminary studies we examined the frequency, functional and phenotypic status of CD8 T cells to determine whether they were altered in chronic ME/CFS donors as compared to healthy donors. We observed an increased CD4:CD8 ratio, altered expression of exhaustion/activation markers like CTLA4 and 2B4 on CD8 T cells, and decreased production of IFNg, TNFa and CD107a/b upregulation following PMA stimulation, all suggesting CD8 T cell exhaustion. This was associated with a, perhaps compensatory increased frequency of activated CD4+CD8+ T cells in the ME/CFS donors as compared to healthy controls. Notably, a subset of the CD8 and the CD4+CD8+ T cell populations were spontaneously producing atypical cytokines, subdividing ME/CFS donors into two subsets: type 1 had an increased frequency of FoxP3+helios+ Treg-like cells producing IL9 (female donors); type 2 had FoxP3+helios- cells producing IL17 (male donors). When we examined the T-cell receptor (TCR) repertoire of the CD4+CD8+ T cell population we found evidence of antigen driven clonal expansions to an unknown antigen at this time, whether it will be a viral or auto-antigen. We hypothesize that the common theme in ME/CFS is an aberrant response to an immunological trigger like infection, which results in a permanently dysregulated immune system as a result of CD8 T cell exhaustion. These studies will identify potential biomarkers and mechanisms driving the immunopathogenesis of ME/CFS leading to future therapies. We will explore this hypothesis in the following Aims. Aim 1 we will examine altered CD8 and CD4+CD8+ T-cell responses in ME/CFS: 1) we will determine if the level of CD8 T cell exhaustion varies with ME/CFS type 1 (female) and Type 2 (male) response and with the severity of ME/CFS symptoms using a larger ME/CFS cohort; 2) we will examine EBV antigen-specific responses in ME/CFS donors to determine if a common persistent virus response is altered by the immunosuppressive state of CD8 T cell exhaustion and further contributing to the disease state of ME/CFS; 3) microarray analyses will be done on sorted activated T cell subsets to assist in understanding the alterations in the functionality of the exhausted and activated CD8 and CD4+CD8+ T cell subsets in ME/CFS donors. In Aim 2 we will examine TCR repertoire of CD8 and CD4+CD8+ T-cell subsets for evidence of antigen driven clonal expansion. Defining the characteristics of the activated clonally expanded CD8 and CD4+CD8+ T cells would be a major step in the field potentially leading to the identification a specific infectious or auto-antigen response that could be the main driver of CD8 T cell exhaustion and the immunological basis of ME/CFS.
Ramsay Award (2020)
“Altered T cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)”Principal Investigators: Liisa Selin MD PhD, Anna Gil PhD, University of Massachusetts Medical School.