Contact information
Marcin Pekalski
MRes PhD
Principal Scientist
Immunology, host microbiota interactions, immunotherapy, immune genetics, immune repertoire, data scientist, metagenomics, immune aging
After completing an MRes in Molecular Biology at Jagiellonian University and doctoral studies in Immunology at the University of Newcastle, I moved to the University of Cambridge to take up a Senior Research Associate position.
I am currently based at the Department of Peadiatrics, Wellcome Centre for Human Genetics, University of Oxford where I investigate genetic and environmental determinants of autoimmunity, link them with immune system function and develop T1D immunotherapies. This has led to a number of insights into T cell biology and two mechanistic trials using IL-2 as an intervention.
After discovering antimicrobial receptors on recent thymic emigrants in neonates and adults, I hypothesised peripheral Treg induction to commensal mimotopes as the regulatory mechanism, entangled with thymic Tregs, conferring tolerance to human epitopes. I am particularly interested in linking the causal role of microbial dysbiosis, an environmental trigger of T1D, with host genetics (HLA class II, INS, PTPN22 and IL-2 pathway) and the immune repertoire (TCRs) against commensal mimotopes, in the aetiology of T1D*.
I am currently designing mechanistic microbiome intervention studies and author of the SINT1A trial at GPPAD and lead for microbiome research at PTChA. In this way, I am applying my experience in prevention strategies including dietary interventions to eradicate diseases linked with microbiome pathologies, in particular T1D, generating insights into the biology of the host-microbial interaction.
Key words: host-microbial interaction, autoimmunity, immunology, T cells, RTEs, Tregs, synbiotic, immunotherapy, HLA class II, TCR, IL-2, holobiont, dysbiosis, mimotope, mimicry, dietary fiber;
Major disease focus: Type 1 Diabetes (T1D), Multiple Sclerosis (MS);
Scientific Board member of Polish Society of Autoimmune Diseases: http://ptcha.pl/en/
Citation - Google Scholar: https://scholar.google.com/citations?user=85gPSaAAAAAJ&hl=en
https://www.well.ox.ac.uk/news/new-avenue-in-microbial-defence-in-newborn-children
Current Project Lead:
Peripheral tolerance to insulin is encoded by mimicry in the microbiome
https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1.full
and
HLA-DQβ57, anti-insulin T cells and insulin mimicry in autoimmune diabetes
https://www.medrxiv.org/content/10.1101/2022.05.11.22274678v1
Recent publications
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Low-dose IL-2 reduces IL-21+ T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes
Journal article
Zhang J-Y. et al, (2022), Nature Communications, 13
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Thymocyte regulatory variant alters transcription factor binding and protects from type 1 diabetes in infants.
Journal article
Sandholm N. et al, (2022), Scientific reports, 12
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Supplementation with Bifidobacterium longum subspecies infantis EVC001 for mitigation of type 1 diabetes autoimmunity: the GPPAD-SINT1A randomised controlled trial protocol.
Journal article
Ziegler A-G. et al, (2021), BMJ open, 11
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Chronic Immune Activation in Systemic Lupus Erythematosus and the Autoimmune PTPN22 Trp620 Risk Allele Drive the Expansion of FOXP3+ Regulatory T Cells and PD-1 Expression
Journal article
Ferreira RC. et al, (2019), Frontiers in Immunology, 10
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A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease
Journal article
Peterson LB. et al, (2018), Journal of Autoimmunity, 95, 1 - 14
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The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in patients with type 1 diabetes
Journal article
Seelig E. et al, (2018), JCI Insight, 3
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Cells with Treg-specific FOXP3 demethylation but low CD25 are prevalent in autoimmunity
Journal article
Ferreira RC. et al, (2017), Journal of Autoimmunity, 84, 75 - 86
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Macropinocytic entry of isolated mitochondria in epidermal growth factor-activated human osteosarcoma cells
Journal article
Patel D. et al, (2017), Scientific Reports, 7
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Capturing the systemic immune signature of a norovirus infection: an n-of-1 case study within a clinical trial
Journal article
Cutler AJ. et al, (2017), Wellcome Open Research, 2, 28 - 28
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Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2
Journal article
Pekalski ML. et al, (2017), JCI Insight, 2
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Capturing the systemic immune signature of a norovirus infection: an n-of-1 case study within a clinical trial
Journal article
Cutler AJ. et al, (2017), Wellcome Open Research, 2, 28 - 28
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Human IL-6R hi TIGIT − CD4 + CD127 low CD25 + T cells display potent in vitro suppressive capacity and a distinct Th17 profile
Journal article
Ferreira RC. et al, (2017), Clinical Immunology, 179, 25 - 39
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In-depth immunophenotyping data of IL-6R on the human peripheral regulatory T cell (Treg) compartment
Journal article
Ferreira RC. et al, (2017), Data in Brief, 12, 676 - 691
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Capturing the systemic immune signature of a norovirus infection: an n-of-1 case study within a clinical trial
Journal article
Cutler AJ. et al, (2017), Wellcome Open Research, 2, 28 - 28
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A rareIL2RAhaplotype identifies SNP rs61839660 as causal for autoimmunity
Journal article
Rainbow DB. et al, (2017)
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Capturing the systemic immune signature of a norovirus infection: an n-of-1 case study within a clinical trial.
Journal article
Cutler AJ. et al, (2017), Wellcome open research, 2
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In-depth immunophenotyping data of IL-6R on the human peripheral regulatory T cell (Treg) compartment
Journal article
Ferreira RC. et al, (2017), DATA IN BRIEF, 12, 676 - 691
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Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial
Journal article
Todd JA. et al, (2016), PLOS Medicine, 13, e1002139 - e1002139
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Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs
Journal article
Gammage PA. et al, (2016), Nucleic Acids Research, 44, 7804 - 7816
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Standardizing Flow Cytometry Immunophenotyping Analysis from the Human ImmunoPhenotyping Consortium
Journal article
Finak G. et al, (2016), Scientific Reports, 6
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Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study
Journal article
Truman LA. et al, (2015), BMJ Open, 5, e009799 - e009799
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Epigenetic analysis of regulatory T cells using multiplex bisulfite sequencing
Journal article
Rainbow DB. et al, (2015), European Journal of Immunology, 45, 3200 - 3203
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Dissection of a Complex Disease Susceptibility Region Using a Bayesian Stochastic Search Approach to Fine Mapping
Journal article
Wallace C. et al, (2015), PLOS Genetics, 11, e1005272 - e1005272
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Widespread seasonal gene expression reveals annual differences in human immunity and physiology
Journal article
Dopico XC. et al, (2015), Nature Communications, 6
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IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients
Journal article
Ferreira RC. et al, (2015), Diabetologia, 58, 781 - 790
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Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells
Journal article
Bell CJM. et al, (2015), Journal of Autoimmunity, 56, 66 - 80
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Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes
Journal article
Thompson WS. et al, (2014), Clinical and Experimental Immunology, 177, 571 - 585
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Investigation of Soluble and Transmembrane CTLA-4 Isoforms in Serum and Microvesicles
Journal article
Esposito L. et al, (2014), The Journal of Immunology, 193, 889 - 900
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A Type I Interferon Transcriptional Signature Precedes Autoimmunity in Children Genetically at Risk for Type 1 Diabetes
Journal article
Ferreira RC. et al, (2014), Diabetes, 63, 2538 - 2550
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Functional IL6R 358Ala Allele Impairs Classical IL-6 Receptor Signaling and Influences Risk of Diverse Inflammatory Diseases
Journal article
Ferreira RC. et al, (2013), PLoS Genetics, 9, e1003444 - e1003444
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Postthymic Expansion in Human CD4 Naive T Cells Defined by Expression of Functional High-Affinity IL-2 Receptors
Journal article
Pekalski ML. et al, (2013), The Journal of Immunology, 190, 2554 - 2566
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Type 1 Diabetes-Associated IL2RA Variation Lowers IL-2 Signaling and Contributes to Diminished CD4+CD25+ Regulatory T Cell Function
Journal article
Garg G. et al, (2012), The Journal of Immunology, 188, 4644 - 4653
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CD25 expression defines novel subsets of naive human CD4+T cells
Conference paper
Pekalski ML. et al, (2011), IMMUNOLOGY, 135, 142 - 142
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Reduced Expression of IFIH1 Is Protective for Type 1 Diabetes
Journal article
Downes K. et al, (2010), PLoS ONE, 5, e12646 - e12646