Niklas Björkström group - Human tissue-resident NK cells

Natural killer (NK) cells

Moreover, we have an interest in the role of natural killer (NK) cells in the pathogenesis of liver diseases such as primary sclerosing cholangitis, steatohepatitis (NASH), and hepatitis virus infections (HBV, HCV, HDV). These diseases strongly predispose for tumor development in the human liver and we are also performing tumorimmunological studies evaluating the capacity of NK cells to recognize hepatocellular carcinoma and cholagiocarcinoma. Outside the liver, we also have an interest in NK-cell function during hemorrhagic fever virus infections.

Our studies include phenotypic and functional assessments of NK cells with a focus on differentiation, education, and functional and transcriptional regulation. We work with high-dimensional 22-parameter flow cytometry, CyTOF, microscopy techniques, and new tools for visualization and analysis of highly complex flow cytometry data including SPADE, SNE, and Citrus.

Current funding

• ERC Starting Grant (2021-2025)
• VR Establishment Grant (Ponzetta, 2021-2024)
• VR Establishment Grant (Ivarsson, 2021-2024)
• VR Establishment Grant (Cornillet, 2021-2024)
• NovoNordisk Foundation Ascending Investigator Grant (2022-2026)
• Swedish Cancer Foundation (2021-2023)
• VR Clinical Scientist grant (2019-2024)
• Swedish Foundation for Strategic Research – Future Research Leader Grant (2017-2021)
• Wallenberg Academy Fellow Grant (2017-2021)
• CIMED Young Investigator Grant (2017-2021)
• Stockholm County Council ALF-funding (2017-2022)

Past funding (2011-2020)

• Swedish Cancer Society (2018-2020)
• Swedish Cancer Society (2015-2017)
• Swedish Research Council Young Investigator Grant (2015-2018)
• Swedish Society for Medical Research (2015-2018)
• NovoNordisk Foundation Young Excellence Project (2015-2019)
• Karolinska Institutet CSTP-grant (2015-2018)
• Cancer Research Foundations of Radiumhemmet (2014-2018)
• Karolinska Institutet KID-grant (2014-2017)
• Karolinska Institutet Assistant Professor Tenure Track Grant (2014-2017)
• Wallströms Foundation
• Magtarm-fonden
• Julins Foundation
• Swedish Society of Medicine
• Bengt Ihre Foundation
• Nanna Svartz Foundation
• Magnus Bergwalls Foundation
• OE och Edla Johanssons Foundation
• Åke Olsson Foundation
• Groschinsky Foundation
• Jaenssons Foundation
• Hedlunds Foundation
• Åke Wibergs Foundation

Group leader

Niklas Björkström's research focuses on human tissue-resident NK cells with a particular emphasis on uterine and liver NK cells.

Niklas received his M.D. and Ph.D. degrees from Karolinska Institutet in 2011. He completed postdoctoral training at the National Institutes of Health in Bethesda, Maryland, USA. Niklas established an independent laboratory at the Center for Infectious Medicine (CIM) in 2013. He is Associate Professor at Karolinska Institutet since 2016. 

In his spare time, Niklas enjoys fly fishing and playing golf.

Group members

Ruth Baumgartner received her MD from the Medical University of Vienna in 2019 and is currently a resident in oncology at Karolinska University Hospital.

Her PhD aims at improving the outcome of patients with cancer in the liver. The clinical part of her studies focuses on a serious complication after liver surgery, post-hepatectomy liver failure. In the Niklas Björkström group, she studies the impact of the tumour immune microenvironment on clinical outcome in cholangiocarcinoma and colorectal cancer liver metastases.

In her spare time, Ruth enjoys hiking and skiing in the Alps, travelling and exploring nature or reading a good book.

Martin Cornillet is focusing on the development of Mass Cytometry to analyse immune cells, particularly NK-cell phenotype and function in different contexts relating to liver physiology/pathophysiology.

He finished his PhD in 2014 that concerned the study of specific autoantibodies in Rheumatoid arthritis (Toulouse, France).

In his spare time, Martin likes cooking, practicing sports like karate, tennis and football. He is also interested in art and music discovering.

Lena Berglin is specialized within the field of immunohistochemistry and quantitative image analysis, techniques that she assists other group members with, as well as collaborators outside the group.

Lena obtained her PhD from Karolinska Institutet in 2015. During her research studies, her main focus was to try to understand how the immune system contributes to the pathogenesis of primary sclerosing cholangitis (PSC) and bile duct cancer.

In her spare time, Lena likes spending time in the countryside, cooking and reading crime novels.

Martin is leading the team Human uterine immune cells in endometrium and pregnancy within the Niklas Björkström group.

Martin received his PhD from KI in 2014 and then focused on the development of human fetal natural killer (NK) cells. He then received a Wenner-Gren postdoctoral fellowship and used this to conduct postdoctoral studies at University of Cambridge, UK. There he developed his interest for uterine immunology and in 2017 he returned to CIM to establish this line of research.

Since 2018 he is an Assistant Professor and in 2020, he was awarded a startup grant from Swedish Research Council (Vetenskapsrådet) to further study uterine immunology.

When Martin is not working, he enjoys spending time with his two daughters, to go for a run and to sample new food and drinks.

Iva Filipovic pursues her research interests in studying the roles of tissue-resident NK cells in the context of uterine and liver microenvironments in homeostasis and pathology.

Iva completed her MSc in Immunology at Imperial College London where she studied NK cell development. She then went on to complete a PhD at the University of Cambridge in the field of reproductive immunology, with a particular focus on phenotypic and transcriptomic characterisation of tissue-resident innate lymphocytes in the uterus.

When not at work, Iva enjoys fitness, music and photography. 

Achilleas Fardellas is investigating the role of ADAR1 in myeloid cells in health and diseases such as nonalcoholic fatty liver disease and obesity.

Achilleas obtained his Pharmacy Master’s degree from the University of Patras followed by a Master’s degree in Toxicology at Karolinska Institutet. Before joining for his PhD studies, he was recruited in an early career talent graduate programme from AstraZeneca for two years where he rotated in three different placements across the R&D pipeline.

In his spare time, Achilleas enjoys dancing, bouldering, and travelling abroad.

During his postdoctoral studies, Christopher Maucourant will characterize tissue-resident NK cells from multiple human tissues, as well as studying the immune response during liver cirrhosis.

Christopher received his Master Degree in immunology and cancerology in 2016. He completed his PhD in 2019 at Sorbonne University in Paris, France, in the field of the signaling pathways involved in NK cells during different arbovirus infections.

When not at work, Christopher enjoys athletics (competition at national and international level), cooking, playing piano and to travel.

Benedikt Strunz graduated 2014 as a MD and additionally accomplished a Bachelor's degree in Biology from the University of Tuebingen in Germany. His PhD-studies in the Niklas Björström group, focused on NK cells in viral infections as well as on uterine NK cells. He defended his thesis in 2020. Benedikt is now combining postdoctoral work in the group with training in clinical microbiology.

In his spare time, Benedikt likes sports like cross country skiing and rowing, enjoys music and jazz concerts. He loves the cinema.

Natalie Stiglund is studying the role of NK-cells in fatty liver disease and development of steatohepatitis and hepatocellular carcinoma. She received her M.D. from Karolinska Institutet in 2016.

In her spare time, Natalie enjoys playing tennis, reading, and travelling.

Jonna Bister is studying uterine NK cell development as well as factors regulating KIR repertoire formation in the uterus. Jonna received her MD from Karolinska Institutet in 2018.

In her spare time Jonna enjoys travelling and go to restaurants.

Emma Patey is studying the cellular ontogeny of innate lymphocytes seeding peripheral tissues in murine models, and will later focus on understanding the role of NK cells in the human uterus in the context of pregnancy.

Emma received her integrated Masters degree in Immunology from the University of Glasgow in 2020. Her Masters placement at Institut Pasteur involved understanding the role of epigenetic modifications on host-pathogen interactions.

In her free time, Emma enjoys socializing with friends, hiking and eating in restaurants.

Daniel Geanon's studies focuses on tissue resident T and NK cells in inflammatory diseases, as well as contributing to KI's ongoing COVID-19 research effort.

Daniel earned his Bachelor's degree in Biology and Global Health at Washington University in St. Louis in 2017. More recently, he worked as an Associate Researcher at Mount Sinai's Human Immune Monitoring Center in New York, New York. There, he focused on leveraging systems level immune profiling technologies (i.e. CyTOF, scRNA-seq) in a diverse range of translational research projects, from profiling tumor infiltrating lymphocytes in cancer to peripheral blood immunophenotyping in COVID-19 and MIS-C.

In his spare time, Daniel enjoys playing football and spending time outdoors hiking and cycling.

As a PhD student, Corinna Mayer profiles uNK cells from patients undergoing IVF treatment and patients suffering from neutropenia which allows her to tackle questions about the outcome of pregnancies, and the role of neutrophils on uNK cells. Besides projects focusing on reproductive immunology, Corinna works on COVID-19 related projects.

Corinna earned her Master’s degree in Biomedicine at Karolinska Institutet in 2021. Her MSC thesis project was bout the expression and function of CD96 (Tactile) on uterine NK (uNK) cells, supervised by Martin Ivarsson.

In her spare time, Corinna likes being outside, spending time with family and friends and eating good food, especially pastries.

As a research assistant, Katharina Schott is in charge of biobanking cells from uterine tissues that are instrumental for several projects. In addition she is involved in various experimental work. Katharina received her Master’s degree at the University of Vienna in 2021.

In her free time, Katharina enjoys travelling, being out in nature and baking.

Andrea Ponzetta is leading the team Unconventional T cells in human pathology within the Niklas Björkström research group. Andrea has been at CIM since 2020. He is currently interested in the biology of innate-like lymphocytes and in their impact in human tumors.

In 2014 Andrea completed his PhD in Immunology at Sapienza University of Rome, where he focused on NK cell trafficking and development. He then moved as a postdoctoral fellow to Humanitas Clinical and Research Center in Milan to study the role of neutrophils in carcinogenesis in solid tumors and their interaction with unconventional T cells.

When not at work, Andrea enjoys travelling, cooking and hiking.

Itzel Medina is part of Andrea Ponzetta´s research team, studying the functional potential of unconventional T cells in human pathology.

Itzel received her PhD in Biomedical Science in 2022 at National Autonomous University of Mexico, FES-Iztacala. Her research project was focused on determining the impact of macrophages without the IL-4Rαexpression during colon cancer associated with inflammation. She also collaborated in other projects that involved the role of regulatory T cells in colon cancer and the secreted and excreted antigens of Taenia crassiceps as modulators of inflammation.

In her free time, Itzel enjoys drawing, listening to music, reading classic novels and visiting new places.

As Postdoctoral researcher, Annika Niehrs studies the dynamics of tissue-residency in a model of liver transplantation and immune cell responses in the context of chronic HBV infection. Annika obtained her PhD from the University of Hamburg in 2019 focusing on the identification of new receptor-ligand interactions for human NK cells.

When not at work, Annika enjoys reading, going to restaurants and being in nature.

At CIM, Jules Russick works on the tissue-resident NK cell in HCC.

Jules completed his PhD in Immunology at Centre de Recherche des Cordeliers in Paris, where he studied the anti-FVIII immune response in hemophilia A. For his first postdoctoral position, he joined Isabelle Cremer’s lab which works on the tumor microenvironment (TME) in lung cancer. His project aimed at analyzing NK cell functions and maturation in human sample and in a murine model of lung cancer.

When not at work, Jules enjoys cooking, climbing and travel.

In 2022 Rebecca Maltez began her PhD studies in the Andrea Ponzetta team, where she is studying dynamic alterations of the immune landscape in gastroesophageal cancer (GEAC).  

Rebecca obtained her MSc degree in Biomedicine from Karolinska Institutet in 2021. Her MSc thesis project focused on the role of FOXO1 and FOXO3 transcription factors in human NK-cell maturation and function. After finishing the MSc degree, Rebecca worked as a research engineer with the Human Protein Atlas, where she mapped subcellular protein localization. 

In her spare time, Rebecca enjoys baking cakes and painting. She also likes to spend time outdoors and tending to her garden.

At CIM, Meredith performs omics data analysis of patient samples in collaboration with other researchers.

She completed her PhD in bioinformatics in 2019 at the Georgia Institute of Technology, focusing on integrating genetic, transcriptomic, and epigenetic data analysis to investigate sex chromosome evolution in birds. After graduation, Meredith worked as a bioinformatician in the bioinformatics service core at MD Anderson cancer center, where she was involved in multiple projects, including how B cells could contribute to anti-tumor immunity.

In her spare time, she enjoys reading novels and listening to podcasts. 

Previous members

• Sanna Nyström, now postdoc at University of Tokyo
• Kimia Maleki, master-student, now PhD-student at Karolinska Institutet
• Sebastian Lunemann, now postdoc at University Medical Center Hamburg-Eppendorf
• Julia Hengst, now Production Manager at Miltenyi Biotech
• Erik Bergquist, now MD-student at Karolinska Institutet
• Otto Strauss, now working in Medical Affairs in Rare Diseases at Pfizer in London. 
• Christine Zimmer, now working at Glaxo Smith Kline, Germany, but will soon proceed with postdoctoral studies.
• Isabella Sönnerborg now Physician at Kalmar Regional Hospital
• Laura Hertwig, now Flow Operations Technical Lead at Covance, Genève
• Ann-Charlotte Elkan, previously PhD, Research nurse, now retired

Selected publications

A complete publication list can be found on PubMed or with citation information in Google Scholar.

2021

1. Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy
   Strunz, B., Bister, J., Jönsson, H., Filipovic, I., Crona-Guterstam, Y., Kvedaraite, E., Sleiiers, N., Dumitrescu, B., Brännström, M., Lentini, A., Reinius, B., Cornillet, M., Willinger, T., Gidlöf, S., Hamilton, RS., Ivarsson, MA., Björkström, NK. Published in Science Immunology
    
2. Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity
   Kvedaraite, E., Hertwig, L., Sinha, I., Ponzetta, A., Hed Myrberg, I., Lourda, M., Dzidic, M., Akber, M., Klingström, J., Folkesson, E., Rao Muuva, J., Chen, P., Gredmark-Russ, S., Brighenti, S., Norrby-Teglund, A., Eriksson, LI., Rooyackers, O., Aleman, S., Strålin, K., Ljunggren, HG., Ginhoux, F., Björkström, NK., Henter, JI., Svensson, M; Karolinska KI/K COVID-19 Study Group. Published in PNAS
    
3. A heterozygous germline CD100 mutation in a family with primary sclerosing cholangitis
   Jiang, X., Bergquist, A., Löscher, BS., Venkatesh, G., Mold, JE., Holm, K., Jaerdahl, JK., Skånland, SS., Maleki, KT., Cornillet, M., Taskén, K., Franke, A., Karlsen, TE., Björktröm, NK*., Melum, E*. *Shared senior authors
   Published in Science Translational Medicine
   
   In the media: KI News
    
4. Natural killer cells in antiviral immunity
   Björkström, NK., Strunz, B., Ljunggren, HG. Published in Nature Reviews Immunology
    
5. COVID-19-specific metabolic imprint yields insights into multiorgan system perturbations
   Cornillet M, Strunz B, Rooyackers O, Ponzetta A, Chen P, Muvva JR, Akber M, Buggert M, Chambers BJ, Dzidic M, Filipovic I, Gorin JB, Gredmark-Russ S, Hertwig L, Klingström J, Kokkinou E, Kvedaraite E, Lourda M, Mjösberg J, Maucourant C, Norrby-Teglund A, Parrot T, Perez-Potti A, Rivera-Ballesteros O, Sandberg JK, Sandberg JT, Sekine T, Svensson M, Varnaite R; Karolinska KI/K COVID-19 Study Group, Eriksson LI, Aleman S, Strålin K, Ljunggren HG, Björkström NK.
   Published in European Journal of Immunology
    
6. Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma
   Zimmer CL, Filipovic I, Cornillet M, O'Rourke CJ, Berglin L, Jansson H, Sun D, Strauss O, Hertwig L, Johansson H, von Seth E, Sparrelid E, Dias J, Glaumann H, Melum E, Ellis EC, Sandberg JK, Andersen JB, Bergquist A, Björkström NK.
   Published in Hepatology
    
7. Natural killer cells and unconventional T cells in COVID-19
   Björkström NK, Ponzetta A.
   Published in Current Opinion in Virology
    
8. A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells
   Zimmer CL, von Seth E, Buggert M, Strauss O, Hertwig L, Nguyen S, Wong AYW, Zotter C, Berglin L, Michaëlsson J, Hansson MR, Arnelo U, Sparrelid E, Ellis ECS, Söderholm JD, Keita ÅV, Holm K, Özenci V, Hov JR, Mold JE, Cornillet M, Ponzetta A, Bergquist A, Björkström NK. Published in Science Translational Medicine
   
   In the media: KI News

2020

1. The identity of human tissue-emigrant CD8+ T cells
   Buggert, M., Vella, LA., Nguyen, S., Wu, V., Chen, Z., Sekine, T., Perez-Potti, A., Maldini, CR., Manne, S., Darko, S., Ransier, A., Kuri-Cervantes, L., Sada Japp, A., Bukh Brody, I., Ivarsson, MA., Gorin, JB., Rivera-Ballesteros, O., Hertwig, L., Antel, JP., Johnson, ME., Okoye, A., Picker, L., Vahedi, G., Sparrelid, E., Llewellyn-Lacey, S., Gostick, E., Sandberg J., Björkström, NK., Bar-Or, A., Dori, Y., Naji, A., Canaday, DH., Laufer, TM., Wells, AD., Pricve, DA., Frank, I., Douek, DC., Wherry, EJ., Itkin, MG., Betts, MR.
   Published in Cell
   
   In the media: KI News
    
2. MAIT cell activation and dynamics associated with COVID-19 disease severity
   Parrot, T., Gorin, JB., Ponzetta, A., Maleki, KT., Kammann, T., Emgård, J., Perez-Potti, A., Rivera-Ballesteros, O., the Karolinska COVID-19 Study Group, Gredmark-Russ, S., Rooyackers, O., Folkesson, E., Eriksson, LI., Norrby-Teglund, A., Ljunggren, HG., Björkström, NK., Aleman, S., Buggert, M., Klingström, J., Strålin, K., Sandberg, JK.
   Published in Science Immunology
   
   In the media: KI News
    
3. Natural killer cell immunotypes related to COVID-19 disease severity 
   Maucourant, C., Filipovic, I., Ponzetta, P., Aleman, S., Cornillet, M., Hertwig, L., Strunz, B., Lentini, A., Reinius, B., Brownlie, D., Cuapio Gomez, A., Heggernes Ask, E., Hull, RM., Haroun-Izquierdo, A., Schaffer, M., Klingström, J., Folkesson, E., Buggert, M., Sandberg, JK., Eriksson, LI., Rooyackers, O., Ljunggren, HG., Malmberg, KJ., Michaëlsson, J., Marquardt, N., Hammer, Q., Strålin, K., Björkström, NK.; and the Karolinska COVID-19 Study Group.
   Published in Science Immunology
   
   In the media: The Scientist, KI News, TV4, EurekAlert!
    
4. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19 
   Sekine, T., Perez-Potti, A., Rivera-Ballesteros, O., Strålin, K., Gorin, JB., Olsson, A., Llewellyn-Lacey, S., Kamal, H., Bogdanovic, G., Muschiol, S., Wullimann, D., Kammann, T., Emgård, J., Parrot, T., Folkesson, E., Karolinska COVID-19 Study Group, Rooyackers, O., Eriksson, LI., Henter, JI., Sönnerborg, A., Allander, T., Albert, J., Nielsen, M., Klingström, J., Gredmark-Russ, S., Björkström, NK., Sandberg, JK., Price, DA., Ljunggren, HG., Aleman, S., Buggert, M.
   Published in Cell
   
   In the media: KI News
   Altmetric score >4500, covered in more than 150 news outlets.
    
5. Human endometrial MAIT cells are transiently tissue resident and respond to Neisseria gonorrhoeae 
   Bister, J., Crona Guterstam, Y., Strunz, B., Dumitrescu, B., Haij Bhattarai, K., Özenci, V., Brännström, M., Ivarsson, MA., Gidlöf, S., Björkström, NK. Published in Mucosal Immunology
    
6. Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus.
   Lutckii, A., Strunz, B., Zhirkov, A., Filipovich, O., Rukoiatkina, E., Gusev, D., Lobzin, Y., Fischler, B., Aleman, S., Sällberg, M., Björkström, NK.
   Published in Gut
   
   In the media: KI News
    
7. The cytokine microenvironment regulates the antigen-presenting characteristics of circulating and tissue-resident intestinal ILCs in humans
   Rao, A., Strauss, O., Kokkinou, E., Bruchard, M., Tripathi KP., Schlums, H., Carrasco-Garcia, A., Mazzurana, L., Konya, V., Villablanca, EJ., Björkström, NK., Lindforss, U., Spits, H., Mjösberg J.
   Published in Nature Communications
    
8. MAIT cells are enriched and highly functional in ascites of patients with decompensated liver cirrhosis
   Niehaus, CE., Strunz, B., Cornillet, M., Falk, CS., Schnieders, A., Massoumy, B., Hardtke, S., Manns, MP., Kraft, ARM., Björkström, NK*., Cornberg, M*. shared senior authors
   Published in Hepatology
    
9. Natural Killer Cells as Sensors of Adipose Tissue Stress
   Fernø J, Strand K, Mellgren G, Stiglund N, Björkström NK
   Published in Trends Endocrinology and Metabolism

2019

1. NK cells are activated and primed for skin-homing during acute dengue virus infection in humans
   Zimmer, CL., Cornillet, M., Solà-Riera, C., Cheung, KW., Ivarsson, MA., Marquardt, N., Qiu, LM., Marquardt, N., Leo, YS., Lye, DC., Klingström, J., MacAry, PA., Ljunggren, HG., Rivino, L., Björkström, NK.
   Published in Nature Communications
   In the media: KI News
    
2. Imbalance of Genes Encoding Natural Killer Immunoglobulin-like Receptors and Human Leukocyte Antigen in Patients With Biliary Cancer 
   Cornillet M, Jansson H, Schaffer M, Hertwig L, Berglin L, Zimmer CL, Johansson H, Ellis E, Isaksson B, Gonzalez-Galarza FF, Middleton D, Malmberg KJ, Sparrelid E, Björkström NK.
   Published in Gastroenterology
   
   In the media: KI News
    
3. Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells
   Dias J, Hengst J, Parrot T, Leeansyah E, Lunemann S, Malone DFG, Hardtke S, Strauss O, Zimmer CL, Berglin L, Schirdewahn T, Ciesek S, Marquardt N, von Hahn T, Manns MP, Cornberg M, Ljunggren HG, Wedemeyer H, Sandberg JK, Björkström NK.
   Published in Journal of Hepatology
   
   In the media: KI News

2018

1. Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity
   Strunz B, Hengst J, Deterding K, Manns MP, Cornberg M, Ljunggren HG, Wedemeyer H, Björkström NK
   Published in Nature Communications
   In the media: KI News, SR P1 Vetenskapsradion, Health Europa