Marcus Buggert

Marcus Buggert

Forskarassistent | Docent

Human T-cellsimmunitet mot evolverande virus och cancer

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E-postadress: marcus.buggert@ki.se
Telefon: +46852481008
Besöksadress: Alfred Nobels allé 8, plan 7, 14152 Huddinge
Postadress: H7 Medicin, Huddinge, H7 CIM Buggert, 171 77 Stockholm
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Om mig

  • Docent och forskargruppsledare vid Karolinska Institutet. Forskningen fokuserar på human adaptiv immunitet vid virusinfektioner och cancer, med särskilt fokus på antigenspecifika T-celler. Genom att studera immunsvar i både blod och vävnader syftar vår forskning till att förstå hur faktorer som lokalisation, ålder, genetik och sjukdom påverkar skyddande respektive dysfunktionell immunitet. Dessa insikter används för att utveckla förbättrade vacciner, immunterapier och strategier för framtida pandemier.

Forskningsbeskrivning

  • Vår forskning

    Vår forskargrupp fokuserar på att öka förståelsen för human cellmedierad immunitet, särskilt hur minnes-T-celler känner igen och eliminerar snabbt föränderliga virusinfektioner och cancer. Dessa patogener och maligna celler kan mutera snabbt och därigenom undvika immunförsvarets antikroppssvar. T-celler har dock en unik förmåga att korsreagera mot sådana förändringar och kan därmed ge ett robust skydd.

    Vi är särskilt intresserade av CD8+ T-celler, som är avgörande för kontroll av de flesta evolverande virusinfektioner och spelar en central roll i moderna cancerterapier. Genom att studera hur dessa celler anpassar sig till snabba förändringar i sjukdomar strävar vi efter att utveckla mer effektiva vacciner och immunterapier.


    Studier av humana minnes-T-celler

    Vår forskargrupp bedriver både grundläggande och translationella studier av humana minnes-T-celler.

    I vår grundforskning undersöker vi heterogenitet, virusspecificitet och funktion hos minnes-T-celler i olika vävnader, med hjälp av en etablerad human organdonatorkohort (IHOPE) samt mer specifika vävnadskohorter. Vi studerar också hur dessa celler kontrollerar tumörer och virusinfektioner såsom HIV, SARS-CoV-2 och influensa, både i vävnader och i blod.

    Vi utvecklar även organoidmodeller för att studera och förstå aktivering och differentiering av minnes-T-celler vid bekämpning av virusinfektioner och tumörer. Vidare använder vi CRISPR-Cas9-baserade knockout-studier för att undersöka hur specifika molekyler påverkar T-cellers funktion. Våra studier utnyttjar också unika tvärsnitts-, longitudinella och vaccinkohorter för att analysera hur faktorer som ålder, genetik och samsjuklighet påverkar både cirkulerande och vävnadsresiderande antivirala minnes-T-celler.

    I vår translationella forskning utvecklar vi avancerade diagnostiska metoder för att analysera T-cellers specificitet och funktion inom precisionsmedicin. Vi deltar även i flera vaccinprövningar för att undersöka hur mRNA-vacciner inducerar funktionella T-cellsvar mot evolverande virus och cancer i individanpassade sammanhang. Dessutom använder vi avancerade teknologier för att utveckla mRNA-baserade terapier och nästa generations CAR-T-cellsbehandlingar, anpassade för att möta utmaningar kopplade till snabbt föränderliga virus, cancer och andra sjukdomar.

    Teknologier och metoder

    Vår forskargrupp använder en bred uppsättning avancerade teknologier för att studera funktioner hos humana minnes-T-celler. Vi har tillgång till multiparametriska flödescytometrar, inklusive både spektrala (upp till 45 parametrar) och konventionella (upp till 30 parametrar) FACS-instrument och sortersystem. Detta möjliggör avancerade single-cell-analyser på proteinnivå.

    Vår laboratorieinfrastruktur inkluderar även 10X Genomics-system, PCR-instrument, bioanalyzers och annan nödvändig utrustning, vilket gör det möjligt att genomföra analyser såsom single-cell RNA-seq, ATAC-seq, CITE-seq, TCR-seq och tetramer-barcoding internt. Vi utvecklar och använder också organoidmodeller från olika vävnader för att efterlikna immunologiska processer i fysiologiskt relevanta miljöer.

    Dessutom har vi utrustning för CRISPR-Cas9-baserade knock-in- och knockout-studier. Vår grupp har även tillgång till högkapacitetssekvensering (t.ex. NovaSeq) och bioinformatisk expertis, vilket ytterligare stärker våra analytiska möjligheter. Tillsammans möjliggör detta omfattande studier av T-cellsbiologi i både hälsa och sjukdom.

    Samarbeten

    Vår forskargrupp är verksam i den dynamiska forskningsmiljön vid Center for Infectious Medicine (CIM) i ANA Futura vid Karolinska Institutet. Vi arbetar nära andra forskargrupper inom CIM och samarbetar med kliniker vid Karolinska Universitetssjukhuset för att få tillgång till värdefulla patientprover. Vi har även omfattande samarbeten med forskare vid Karolinska Institutet och SciLifeLab i Sverige, samt med ledande forskare inom vårt fält vid universitet världen över.

Artiklar

Alla övriga publikationer

Forskningsbidrag

  • Swedish Research Council
    1 January 2026 - 31 December 2028
    Double-negative αβ T cells (DNTαβ) are an underexplored subset of human T cells lacking CD4 and CD8 co-receptors. While extensively studied in mouse models, findings on their functional plasticity and role in tumor immunity may not fully translate to humans. Human DNTαβ cells exhibit substantial heterogeneity, but their developmental origins, antigen specificity, and functional relevance remain unclear.This project aims to systematically map human DNTαβ diversity, establish their developmental hierarchy, and determine their role in metastatic gastric cancer (GC). A combination of unique human sample collections and a novel in vitro expansion system enables us to study DNTαβ with unprecedented resolution. Using single-cell RNA and TCR sequencing, advanced flow cytometry, and functional assays, we will define the mechanisms driving DNTαβ activation, differentiation, and tumor reactivity.Our findings will clarify whether DNTαβ functionally overlap with conventional αβ T cells or represent a distinct immune subset. We will establish their antigen specificity, molecular drivers of activation, and potential interactions with the tumor microenvironment. Additionally, we will assess their prognostic value in cancer patients and explore whether specific DNTαβ subsets could be harnessed for cell-based immunotherapy or biomarker discovery.
  • Swedish Research Council
    1 December 2025 - 30 November 2028
    CCHFV is one of the most lethal tick-borne viruses, with high mortality and rapid geographic expansion driven by climate change. Despite its classification by the WHO as a priority pathogen, vaccine development is hampered by limited understanding of protective immune mechanisms, particularly T cell responses. This project aims to close that gap by uncovering how adaptive immunity,with focus to T cells , shapes protection during natural infection and vaccination. Leveraging one of the world’s largest longitudinal biobanks of CCHFV patients, in combination with cutting-edge animal models and advanced single-cell technologies, we will define the phenotype, function, and antigen-specificity of virus-specific T cells. Our dual focus is: (i) elucidating T cell dynamics in human infection, and (ii) mapping protective T cell responses in vaccine recipients. Preliminary data suggest T cells, rather than neutralizing antibodies, play a central role in controlling disease. Our integrated approach combines systemic and tissue-level immunoprofiling, functional assays, and peptide epitope mapping to identify immune correlates of protection. This cross-sectoral collaboration unites academia, hospitals, and public agencies to accelerate the development of next-generation vaccines that position immunity where it matters most—at the site of viral entry. The project will redefine vaccine strategies and enhance pandemic preparedness for this neglected but growing global threat.
  • Swedish Research Council
    1 December 2025 - 30 November 2028
    Influenza viruses remain among the greatest and most dynamic global health threats. While seasonal vaccines offer transient protection, they often fail against emerging strains like H5N1 and H7N9. T cells, particularly CD8+ T cells, provide a critical layer of cross-protective immunity by targeting conserved internal viral proteins. However, major gaps remain in understanding how well CD8+ T cells cross-recognize these emerging subtypes, especially within tissues where early immune control is critical. We hypothesize that aging profoundly alters the maintenance, tissue distribution, and recall capacity of conserved influenza-specific CD8+ T cell immunity, contributing to differential vulnerability to seasonal and emerging viruses. To test this, we will leverage unparalleled human resources, including cross-sectional and longitudinal cohorts, organ donor tissues, and ex vivo lymphoid organoid models. First, we will identify conserved CD8+ T cell targets across major influenza subtypes and map their specificity and cross-reactivity in young and elderly individuals. Second, we will dissect how aging impacts the quality and tissue distribution of conserved influenza-specific CD8+T cell immunity. Third, we will interrogate functional recall responses in young and old tissue-derived lymphoid organoid models. Together, this work will build a comprehensive framework for understanding the cross-reactive nature of cellular immunity against influenza across the human lifespan.
  • Swedish Research Council
    1 January 2025 - 31 December 2026
    Current HIV cure trials primarily focus on people living with HIV (PLWH) who started antiretroviral therapy (ART) during the primary infection stage, as they are known to have smaller HIV reservoirs. However, there is a substantial knowledge gap regarding the size of the HIV reservoir in majority of PLWH. Our study aims to address this gap by exploring the size of the HIV reservoir through comprehensive clinical, immunological, and virological assessments, and by developing an algorithm to predict HIV reservoir size.To achieve this, the CHART-C study will include 200 PLWH on long-term successful ART, with a substudy examining the HIV reservoir in the central nervous system of 20 participants. We will use advanced assays such as IPDA, CADseq method, and quantification of HIV-specific humoral/cellular responses. Machine learning techniques will be employed to develop an algorithm to identify individuals with the smallest HIV reservoirs.The outcome of this study will be a clinical algorithm designed to select individuals with the smallest HIV reservoirs, thereby optimizing the inclusion criteria for future HIV cure trials and enhancing the potential for therapeutic success. Additionally, we will prepare for an analytical treatment interruption  HIV cure trial using two long-acting broadly neutralizing antibodies. The CHART-C trial aims to make a significant contribution to global HIV cure strategies and position Swedish HIV research at the forefront of this critical field.
  • Swedish Research Council
    1 December 2023 - 30 November 2026
    Our goal is: (i) To perform a longitudinal assessment of adaptive immune responses in SARS-CoV-2 mRNA vaccinated immunocompromised patient groups and healthy controls. The rational for the studies is that many of the studied patient groups have an increased risk of developing severe COVID-19 upon SARS-CoV-2 infection. Hence, information on vaccine-induced immune status in real-time in the studied patient groups is important. It serves to provide necessary advice on protective measurements needed to be taken as well as for detemining the need for prophylactic treatment, and upon SARS-CoV-2 infection, need for immediate treatment. (ii) To perform a deep assessment of adaptive immune responses in SARS-CoV-2 mRNA vaccinated immunocompromised patients and healthy controls. The rational for the studies is that it is currently unknown to what extent multiple SARS-CoV-2 mRNA vaccine doses may over time affect qualitative aspects of the adpative immune response generated. The latter informtion may impact future vaccine design and/or vaccination strategies. (iii) To undertake long-term capacity building for very rapidly being able to assess prevailing immunity in SARS-CoV-2 mRNA vaccinated patient groups and healthy controls in the event of an emerging new SARS-CoV-2 variant-of-concern outbreak. The rational being that new emerging variants may escape parts of current vaccine-induced immunity. This may be particular harmful for several of the presently studied patient groups.
  • Swedish Cancer Society
    1 January 2023
    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Sweden. Over the past decade, more targeted therapies that inhibit tumor growth have improved the prognosis of patients with the disease. However, CLL remains incurable, with many patients eventually developing treatment resistance. Many patients also suffer from other complications, such as infectious diseases - this has not least been witnessed in recent years with high mortality in covid-19 in CLL patients. Taken together, this underscores the need to understand why our immune system is unable to eradicate leukemia cells and control various pathogens in patients with CLL. The body's T cells are essential in controlling and eliminating many infections and malignancies. New findings in the CLL field indicate that many T cells put on their 'brakes' by upregulating inhibitory receptors, such as PD-1, and consequently become dysfunctional. This process is known as T cell exhaustion and has been described by us and others for T cells in both malignancies and chronic viral infections. The underlying causes of increased T-cell exhaustion in CLL are currently unknown, but could probably be a contributing factor to T-cells being unable to knock out leukemia cells or potentially control various pathogens. Through a collaboration with leading researchers and clinicians in oncology, hematology and immunology, we want to understand how memory T cells recognize pathogens and leukemia cells in CLL patients. We also want to understand if we can reverse this process and generate more effective immunotherapies.
  • Swedish Research Council
    1 January 2023 - 31 December 2027
    CD8+ T cells are critical to generate immunity to most viral infections. Studies of human blood have been instrumental to advance our understanding of how CD8+ T cells function and can control different viruses. However, most of CD8+ T cells are not found in the blood, but mainly in tissues. This fact, together with the notion that humans respond very differently to the same virus, force a re-evaluation of how different factors, such as genetics and localization, affect antiviral CD8+ T cell differentiation and functions across tissues and blood. We will first use single-cell techniques on unique organ donor samples to establish a reference map of where virus-specific CD8+ T cell clones are preferentially located in the human body (aim 1). Through innovative live-attenuated yellow fever virus vaccination protocols, we will next track how virus-specific CD8+ T cells develop in draining vs. non-draining lymph nodes compared to the blood (aim 2). Using the same vaccine platform, we will finally assess the impact of genetics on circulating memory CD8+ T cell differentiation through studies on monozygotic twins (aim 3). This ambitious, but technically feasible project, will establish a framework for many future immunological studies in the field of antiviral immunity and inform the development of more effective vaccine platforms and immune therapies against future viral threats.
  • Swedish Research Council
    1 January 2023 - 31 December 2027
    CD8+ T cells are critical to generate immunity to most viral infections. Studies of human blood have been instrumental to advance our understanding of how CD8+ T cells function and can control different viruses. However, most of CD8+ T cells are not found in the blood, but mainly in tissues. This fact, together with the notion that humans respond very differently to viral infections, force a re-evaluation of how different factors, such as genetics and localization, affect antiviral CD8+ T cell differentiation and functions across tissues and blood. We will first use single-cell techniques on unique organ donor samples to establish a reference map of where virus-specific CD8+ T cell clones are preferentially located in the human body (aim 1). Through innovative live-attenuated yellow fever virus vaccination protocols, we will next track how virus-specific CD8+ T cells develop in draining vs. non-draining lymph nodes compared to the blood (aim 2). Using the same vaccine platform, we will finally assess the impact of genetics on circulating memory CD8+ T cell differentiation through studies on monozygotic twins (aim 3). This ambitious, but technically feasible project, will establish a framework for many future immunological studies in the field of antiviral immunity and inform the development of more effective vaccine platforms and immune therapies against future viral threats.
  • Swedish Research Council
    1 January 2023 - 31 December 2025
  • Swedish Research Council
    1 December 2022 - 31 December 2026
    Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease COVID-19. During the two years since the virus and the disease was first discovered, COVID-19 has by mid-March 2022 caused at least 480 million infections and 6.2 million deaths world-wide. The pandemic hit unevenly across the world population, with characteristics such as age, male sex, underlying conditions, and host genetics influencing the risk of developing severe disease. Interestingly, available data suggests that East African countries such as Uganda have been relatively less affected in terms of severe COVID-19 disease and mortality compared to many western countries, despite very limited and delayed vaccine availability. In this proposal, we hypothesize that pre-existing T cell immunity to coronaviruses gained before the pandemic may influence these patterns of susceptibility to severe COVID-19. To address this possibility, we will utilize the Ugandan arm of the RV329 African Cohort Study (AFRICOS), which has a retrospective longitudinal set of cryopreserved samples covering pre-pandemic and pandemic time-points. This cohort will also allow us to address the impact of HIV-1 infection on the characteristics of pre-existing immunity. We anticipate that the proposed experiments, together with the comprehensive clinical data collected in the AFRICOS study, will significantly enhance our understanding of the role of pre-existing T cell immunity to protect from severe COVID-19.
  • Swedish Research Council
    1 December 2022 - 30 November 2025
  • Deutsche Forschungsgemeinschaft
    1 January 2022 - 31 December 2024
  • Swedish Research Council
    1 December 2021 - 30 November 2024
  • Swedish Research Council
    1 December 2021 - 30 November 2025
  • Swedish Research Council
    1 June 2021 - 31 May 2025
  • Swedish Heart-Lung Foundation
    1 January 2021 - 31 December 2021
  • Swedish Research Council
    1 January 2021 - 31 December 2023
  • Swedish Research Council
    1 August 2020 - 31 December 2020
  • Swedish Cancer Society
    1 January 2020
    'Immune checkpoint blockade' (ICB) of inhibitory receptors (such as PD-1) has revolutionized cancer treatment. These therapies block the brakes of the immune system (inhibitory receptors) and thereby lead to better recognition of tumor cells for killer T cells. In particular, anti-PD-1 therapy can induce long-term remission and even 'cure' metastatic disease for multiple malignancies. However, far from all patients undergoing anti-PD-1 immunotherapy respond to treatment. This emphasizes the importance of understanding the underlying immunological mechanisms in order to improve ICB therapy in future forms of treatment. In this project, we will study the types of killer T cells that respond to anti-PD-1 immunotherapy and where these cells are located. Our preliminary studies suggest that we can identify persistent and functional killer T cells that express PD-1 in lymph nodes. Through mechanistic studies on animal models that can be translated directly to humans after collecting clinical samples from malignant melanoma and liver cancer, we want to understand whether persistent PD-1 + killer-T cells in draining lymph nodes or tumors are the source of an effective response to anti-PD- 1 immunotherapy. The new generation of immunotherapies has changed the landscape for various cancers. However, a sustainable immune response is limited to a small subset of cancer patients. By identifying which killer T cells respond to this new generation of cancer treatments, we will not only identify a reliable predictive biomarker but also gain insight into how such cells can be further used as targets in combination with PD-1 inhibitors, to extend immunotherapy to more tumor types and a larger population of patients.
  • Swedish Research Council
    1 January 2019 - 31 December 2022
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Anställningar

  • Forskarassistent, Medicin, Huddinge, Karolinska Institutet, 2018-2026

Examina och utbildning

  • Docent, Immunologi, Karolinska Institutet, 2021
  • Medicine Doktorsexamen, Institutionen för laboratoriemedicin, Karolinska Institutet, 2014

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