Yenan Bryceson group

Our work strives to understand the role of lymphocyte cytotoxicity in health and disease, and ultimately harness their potent activity to fight cancer. The aim of the research is to include fundamentally new conceptualizations of immunological disorders, basic immunological and genetic insights, and potent, specific immunotherapeutic interventions for treatment of disease.

Yenan Bryceson Research group. Photo: HERM

Our laboratory is based at the Center for Hematology and Regenerative Medicine (HERM) at Karolinska University Hospital, Huddinge, and employs a wide range of techniques. To gain clinical and scientific insights into human diseases, we collaborate closely with clinicians at Karolinska Institutet, across Scandinavia and the rest of the world.

About our research

Our work strives to understand the role of lymphocyte cytotoxicity in health and disease, and ultimately harness their potent activity to fight cancer. We have developed methods for quantification of human cytotoxic lymphocyte development and function, uncovering key mechanisms for their differentiation and cytotoxic activity. We hope that outcomes of our work will include fundamentally new conceptualizations of immunological disorders, basic immunological and genetic insights, and potent, specific immunotherapeutic interventions for treatment of disease.

In the most severe cases, clinical manifestation of patients with defective lymphocyte cytotoxicity are often triggered by viral infections and elicit uncontrolled immune cell proliferation and hyperinflammatory immune pathology. Otherwise, such mutations may predispose to cancer.

Subsets of lymphocytes, such as cytotoxic T cells and natural killer (NK) cells, can kill infected or malignant cells. Individuals carrying mutations in genes required for such lymphocyte cytotoxicity develop life-threatening disorders, highlighting clinical relevance. Harnessing their differentiation and function represents a promising strategy for cellular immunotherapy.

Keywords

Cellular cytotoxicity, NK cells, cytotoxic T cells, cancer, primary immunodeficiencies, cellular immunotherapy

Yenan Bryceson, Group leader at HERM. Photo: Bosse Johansson/MedH

Group leader

Yenan Bryceson

Professor, PhD
H7 Department of Medicine, Huddinge

Yenan Bryceson received his MSc degree from the University of Oslo, Norway in 2000. He received his PhD from Karolinska Institutet in 2008, after after working in the lab of Eric Long at the National Institutes of Health, Rockville, MD, USA with support from the National Institutes of Health, Karolinska Institutet Graduate Partnership Program.

In his spare time he enjoys hiking, skiing, fly fishing and is also trying to figure out surfing.

Group members

Staff

Sara Von Bahr Grebäck

Project coordinator
H7 Department of Medicine, Huddinge

Jelve Nejati Zendegani

Biomedical scientist
H7 Department of Medicine, Huddinge

Jelve Zendegani joined the Bryceson laboratory in 2014. She performs analyses of patients with suspected immunodeficiencies, in addition to supporting the every-day function of the laboratory. 

Jelve trained as a biomedical analyst in Sweden, receiving her Master degree in Biomedicine from Kalmar University in 1996. She has experience in a variety of molecular biological and immunological techniques from work at Pennsylvania State University USA, King’s College London, and Karolinska Institutet.

In her spare time Jelve enjoys baking, photography, travelling and hiking.

Postdocs

Tessa Campbell

Postdoc
H7 Department of Medicine, Huddinge

Timothy Holmes

Postdoc
H7 Department of Medicine, Huddinge

Tim Holmes received his BSc from the University of Leeds and earned a PhD at the same University in 2009. His current research is focussed on identifying epigenetic differences and transcription factor networks driving cytotoxic cell specification.

In his spare time, Tim enjoys both skiing and snowboarding and has ambitions to learn to kite-surf!

H7 Department of Medicine, Huddinge

Elisa Saccon

Postdoc
H7 Department of Medicine, Huddinge
H7 Department of Medicine, Huddinge

Heinrich Schlums is currently enrolled in the Experimental Medicine Program at Karolinska Institutet. His studies concern human cytotoxic lymphocyte signalling in health and disease.

Heinrich received his MSc degree from the Technical Universtiy of Braunschweig, Germany in 2010.

In his spare time Heinrich enjoys picking mushrooms and tasting wine.

PhD students

Giovanna Perinetti Casoni

Clinical assistant
H7 Department of Medicine, Huddinge

Giovanna Perinetti Casoni is currently enrolled in the Experimental Medicine PhD Program at Karolinska Institutet. Her studies focus in understanding granule exocytosis in cytotoxic lymphocytes and how pathological mutations impair this process.

Giovanna received her BSc in Biotechnology in 2013 from the University of Trieste, Italy. She moved to Trondheim, Norway, and obtained an MSc in Molecular Medicine from the Norwegian University for Science and Technology, NTNU, in 2015.

In her spare time she enjoys synchronized swimming and traveling, and she hopes to ameliorate her skiing skills.

Laura Covill

PhD student
H7 Department of Medicine, Huddinge

Laura Covill started her PhD in the Bryceson laboratory in 2019. She is currently focusing on development of molecular diagnostics in primary immunodeficiencies using genomic, transcriptomic and epigenomic data.

Laura received a BSc in Biochemistry from King’s College London in 2017 and an MRes in Biology from the University of York, UK, in 2018.

In her spare time she enjoys baking and reading.

Petar Mitev

PhD student
H7 Department of Medicine, Huddinge

Master students

 

Blanca González Melarde

Master student

Collaborations

The research in Yenan Bryceson's group is performed with a number of national and international collaborators found in the list below.

  • Dorina Avram, Moffit Cancer Center
  • Kaan Boztug, CeMM
  • Cynthia Dunbar, National Institutes of Health
  • Stephan Ehl, University of Freiburg
  • Olov Ekwall, University of Gothenberg
  • Nelson Gekara, Stockholm University
  • Jan-Inge Henter, Karolinska Institutet
  • Eric Long, National Institutes of Health
  • Jeffrey Miller, University of Minnesota
  • Jens Rettig, University of Saarland
  • Lars Rönnblom, Uppsala University
  • Anna Wedell, Karolinska Institutet

Projects

Current projects in the group encompass studies of cytotoxic lymphocyte development and activation, specifically focusing on the molecular mechanisms of granule release and differentiation. A specific interest is to harness insights for improved cellular immunotherapy of cancer. We also more generally study primary immunodeficiencies with high mortality or morbidity related to viral infections, autoimmunity, and cancer, aiming to understand pathophysiology and develop of improved assays for identification of human immunodeficiencies associated with hyperinflammatory or autoinflammatory.

These projects employ advanced tools in molecular biology, cell manipulation and genome-editing, multiparameter flow cytometry, high-throughput sequencing and advanced cell imaging.

Research support

  • Swedish Research Council
  • Swedish Foundation for Strategic Research
  • Wallenberg Foundation (Wallenberg Academy Fellow)
  • Swedish Cancer Foundation
  • Swedish Children’s Cancer Foundation
  • CIMED
  • ALF
  • Karolinska Institutet Research Foundation

Selected publications

Link to all publications (PubMed)

  1. The transcription factor Bcl11b promotes both canonical and adaptive NK cell differentiation.
    Holmes TD, Pandey RV, Helm EY, Schlums H, Han H, Campbell TM, Drashansky TT, Chiang S, Wu CY, Tao C, Shoukier M, Tolosa E, Von Hardenberg S, Sun M, Klemann C, Marsh RA, Lau CM, Lin Y, Sun JC, Månsson R, Cichocki F, Avram D, Bryceson YT. Sci Immunol 2021 Mar;6(57):
     
  2. RhoG deficiency abrogates cytotoxicity of human lymphocytes and causes hemophagocytic lymphohistiocytosis.
    Kalinichenko A, Perinetti Casoni G, Dupre L, Trotta LC, Huemer J, Galgano D, German Y, Haladik B, Pazmandi J, Thian M, Yüce Petronczki Ö, Chiang SCC, Taskinen MH, Hekkala A, Kauppila S, Lindgren O, Tapiainen T, Kraakman MJ, Vettenranta K, Lomakin AJ, Saarela J, Seppänen MRJ, Bryceson YT, Boztug K. Blood 2021 Jan;():
     
  3. Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria.Hart GT, Tran TM, Theorell J, Schlums H, Arora G, Rajagopalan S, Sangala ADJ, Welsh KJ, Traore B, Pierce SK, Crompton PD, Bryceson YT, Long EO. J Exp Med 2019 06;216(6):1280-1290
     
  4. Clonal expansion and compartmentalized maintenance of rhesus macaque NK cell subsets.
    Wu C, Espinoza DA, Koelle SJ, Yang D, Truitt L, Schlums H, Lafont BA, Davidson-Moncada JK, Lu R, Kaur A, Hammer Q, Li B, Panch S, Allan DA, Donahue RE, Childs RW, Romagnani C, Bryceson YT, Dunbar CE. Sci Immunol 2018 11;3(29):
     
  5. ARID5B regulates metabolic programming in human adaptive NK cells.
    Cichocki F, Wu CY, Zhang B, Felices M, Tesi B, Tuininga K, Dougherty P, Taras E, Hinderlie P, Blazar BR, Bryceson YT, Miller JS. J Exp Med 2018 09;215(9):2379-2395
     
  6. HLH: genomics illuminates pathophysiological diversity.
    Tesi B, Bryceson YT. Blood 2018 07;132(1):5-7
     
  7. A RAB27A 5' untranslated region structural variant associated with late-onset hemophagocytic lymphohistiocytosis and normal pigmentation.
    Tesi B, Rascon J, Chiang SCC, Burnyte B, Löfstedt A, Fasth A, Heizmann M, Juozapaite S, Kiudeliene R, Kvedaraite E, Miseviciene V, Muleviciene A, Müller ML, Nordenskjöld M, Matuzeviciene R, Samaitiene R, Speckmann C, Stankeviciene S, Zekas V, Voss M, Ehl S, Vaiciene-Magistris N, Henter JI, Meeths M, Bryceson YT. J Allergy Clin Immunol 2018 07;142(1):317-321.e8
     
  8. CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin.Cheuk S, Schlums H, Gallais Sérézal I, Martini E, Chiang SC, Marquardt N, et alImmunity 2017 02;46(2):287-300
     
  9. Adaptive NK cells can persist in patients with GATA2 mutation depleted of stem and progenitor cells.Schlums H, Jung M, Han H, Theorell J, Bigley V, Chiang SC, et alBlood 2017 04;129(14):1927-1939
     
  10. Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms.
    Tesi B, Davidsson J, Voss M, Rahikkala E, Holmes TD, Chiang SCC, et alBlood 2017 04;129(16):2266-2279
     
  11. Acquired somatic mutations in PNH reveal long-term maintenance of adaptive NK cells independent of HSPCs. Corat MA, Schlums H, Wu C, Theorell J, Espinoza DA, Sellers SE, et alBlood 2017 04;129(14):1940-1946
     
  12. Natural killer cell memory in context.
    Holmes TD, Bryceson YT. Semin. Immunol. 2016 08;28(4):368-76
     
  13. Epigenetic Regulation of Adaptive NK Cell Diversification.
    Tesi B, Schlums H, Cichocki F, Bryceson YT. Trends Immunol. 2016 07;37(7):451-461
     
  14. CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT.
    Cichocki F, Cooley S, Davis Z, DeFor TE, Schlums H, Zhang B, et alLeukemia 2016 Feb;30(2):456-63
     
  15. Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function.
    Schlums H, Cichocki F, Tesi B, Theorell J, Beziat V, Holmes TD, et alImmunity 2015 Mar;42(3):443-56
     
  16. VAMP8-dependent fusion of recycling endosomes with the plasma membrane facilitates T lymphocyte cytotoxicity. 
    Marshall MR, Pattu V, Halimani M, Maier-Peuschel M, Müller ML, Becherer U, et alJ. Cell Biol. 2015 Jul;210(1):135-51
     
  17. Hemophagocytic lymphohistiocytosis in 2 patients with underlying IFN-γ receptor deficiency.
    Tesi B, Sieni E, Neves C, Romano F, Cetica V, Cordeiro AI, et alJ. Allergy Clin. Immunol. 2015 Jun;135(6):1638-41
     
  18. Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D.
    Meeths M, Chiang SC, Wood SM, Entesarian M, Schlums H, Bang B, et alBlood 2011 Nov;118(22):5783-93
     
  19. Synergistic signals for natural cytotoxicity are required to overcome inhibition by c-Cbl ubiquitin ligase.Kim HS, Das A, Gross CC, Bryceson YT, Long EO. Immunity 2010 Feb;32(2):175-86
     
  20. Regulation of human NK-cell cytokine and chemokine production by target cell recognition.
    Fauriat C, Long EO, Ljunggren HG, Bryceson YT. Blood 2010 Mar;115(11):2167-76