Yenan Bryceson group
We strive to identify molecular causes of hyperinflammatory disorders and understand the role of lymphocyte cytotoxicity in health and disease. We aim to develop new conceptualizations of immunological disorders, and combine basic immunological and genetic insights with potent immunotherapeutic interventions for the development of personalized treatment of disease. Our ultimate goal is to harness fundamental insights of the human immune system to develop cytotoxic cell therapies to fight cancer.
Our laboratory is based at the Center for Hematology and Regenerative Medicine (HERM) at Karolinska University Hospital, Huddinge, which provides access to a wide range of cutting-edge technologies. To gain clinical and scientific insights into human diseases and ultimately flight cancer, we collaborate closely with clinicians and scientists at Karolinska Institutet, across Scandinavia and globally.
About our research
Our lab is focused on gaining molecular insights to the human immune system. One arm is dedicated to determining how inborn errors of immunity can result in life-threatening diseases and impaired immunosurveillance of cancer. We employ these insights to tailor personalized treatments of affected individuals. Another major research direction in our lab strives to understand the cytotoxic lymphocyte biology, and ultimately harness their potent activity to fight 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 hyperinflammatory disorders, highlighting clinical relevance. 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, typically in childhood. In other cases, such mutations may predispose to cancer.
We have developed sensitive methods for quantification of human cytotoxic lymphocyte development and function, uncovering key mechanisms for their differentiation and cytotoxic activity. Furthermore, we have uncovered transcription factors that promote the differentiation of persistent T and NK cells with strong cytotoxic function. Harnessing the differentiation and function of cytotoxic lymphocytes represents a promising strategy for cellular immunotherapy of cancer.
Cellular cytotoxicity, NK cells, cytotoxic T cells, cancer, primary immunodeficiencies, cancer immunotherapy
Yenan received his MSc degree from the University of Oslo, Norway in 2000. He completed his PhD from Karolinska Institutet in 2008, 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.
Research secretary, project coordinator
PA for Professor Eva Hellström Lindberg
PA for Professor Yenan Bryceson
Environment and sustainability representative for MedH
Health promoter for MedH/HERM
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.
Tessa obtained her PhD from the University of Sydney, Australia in 2019, characterising herpesvirus evasion of NK cells. She then started as a postdoctoral researcher in the Bryceson group in 2019. Tessa is funded by a Swedish Foundation for Medical Research (SSMF) fellowship, investigating NK cell homeostasis as well as plasmacytoid dendritic cell function using cases of primary immunodeficiency.
When not in the lab Tessa loves travelling, exploring cafes, bars and forests, and enjoying Stockholm's Italian culture.
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!
Anna Rita received her PhD in Molecular, Integrative and Cellular Biology from University of Lyon (France) in 2020 on the subject of cancer immunotherapy. Her postdoctoral studies are focused on reprogramming NK cells to improve the persistence and infiltration of CAR-NK cells in solid cancers.
In her spare time, she likes to attend concerts and art exhibitions.
Elisa received her PhD in 2019 from the University of Padova (Italy) in virology. She is Postdoctoral Research Fellow in the Bryceson group, funded by the Swedish Cancer Society (Cancerfonden), investigating the molecular mechanisms of SAMD9 and SAMD9L proteins in cellular defense and growth control.
In her spare time, Elisa enjoys going to concerts, hiking and travelling.
Heinrich received his MSc degree from the Technical Universtiy of Braunschweig, Germany in 2010 and his PhD from Karolinska Institutet in 2017, studying human cytotoxic lymphocyte signalling in health and disease. His research continues to focus on NK cell and CD8+ T cell signaling pathways and differentiation.
In his spare time Heinrich enjoys picking mushrooms and tasting wine.
Sigrid received a BSc degree from Maastricht University, the Netherlands (2012) and completed her MSc on ‘Infection and Immunity’ at Utrecht University, the Netherlands (2014). After obtaining her PhD on transcriptional regulation of human NK cell development from the University of Ghent, Belgium (2022), she started her postdoctoral research at the Center of Hematology and Regenerative Medicine (HERM). Her main research interests include the transcriptional regulation of human NK cell function and tissue homing as well as the role of nutrients in these intricate processes.
In her spare time she likes to unwind by doing pilates or by getting immersed into Japanese pop culture.
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. She 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.
In her spare time she enjoys synchronized swimming and traveling, and she hopes to ameliorate her skiing skills.
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. She started her graduate studies in the Bryceson laboratory in 2019. She is currently focusing on development of molecular diagnostics in primary immunodeficiencies using genomic, transcriptomic and epigenomic data.
In her spare time she enjoys baking and reading.
Petar received a BSc in Biochemistry (with a Year-in Research) from Imperial College London in 2016 and obtained an MSc in Pharmacology from the Duke University, US, in 2019. He started his graduate studies in the Bryceson laboratory in 2022. His project focuses on understanding the role and mechanism of action of the human SAMD9 and SAMD9L proteins in the context of cancer development and therapy.
In his spare time, Petar enjoys playing the guitar, chess, and is an avid NFL and NBA fan.
Irina PiiroinenMaster student
Fabian PucherMaster student
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
- Frank Cichocki, University of Minnesota
- 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
- Jeffrey Klco, St Jude’s Hospital
- Claudia Kutter, Karolinska Institutet / SciLifeLab
- Eric Long, National Institutes of Health
- Jens Rettig, University of Saarland
- Lars Rönnblom, Uppsala University
- Anna Wedell, Karolinska Institutet
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. Here we aim to understand disease pathophysiology and develop improved assays for identification of human immunodeficiencies associated with hyperinflammation or autoinflammation.
These projects employ advanced tools in molecular biology, cell manipulation and genome-editing, multiparameter flow cytometry, high-throughput sequencing and advanced cell imaging.
- Swedish Research Council
- Wallenberg Foundation (Wallenberg Academy Fellow)
- Swedish Cancer Foundation
- Center for Innovative Medicine
- Karolinska Institutet Research Foundation
- CD49a expression and induction of cytotoxicity on human tissue-resident CD8+ T cells is controlled by RUNX2 and RUNX3 transcription factor activity.
Zitti B, Hoffer E, Zheng W, Pandey RV, Schlums H, Perinetti-Casoni G, Fusi I, Nguyen TLK, Kärner J, Kokkinou E, Carrasco A, Gahm J, Ehrström M, Haapaniemi S, Keita ÅV, Hedin C, Mjösberg J, Eidsmo L*, Bryceson YT*. Immunity Accepted.
Bcl11b sustains multipotency and restricts effector programs of intestinal resident memory CD8+ T cells. Helm E, Zelenka T, Cismasiu VB, Islam S, Silvane L, Zitti B, Holmes TD, Drashansky TT, Kwaitkowski A, Tao C, Dean J, Obermayer AN, Chen X, Keselopwsky BG, Zhang L, Hou Z, Zhou L, Sheridan BS, Conejo-Garcia JR, Shaw TI, Bryceson YT, Avram D. Science Immunology. In press.
Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency. Campbell TM, Liu Z, Zhang Q, Moncada-Velez M, Covill LE, Alavi Darazam I, Bastard P, Bizien L, Bucciol G, Enoksson SL, Jouanguy E, Karabela SN, Khan T, Kendir Demirkol Y, Arias AA, Mansouri D, Marits P, Marr N, Migeotte I, Moens L, Ozcelik T, Pellier I, Sendel A, Shahrooei M, Smith CIE, Vandernoot I, Willekens K, COVID Human Genetic Effort, Bergman P, Abel L, Cobat A, Casanova JL*, Meyts I*, Bryceson YT*. J Exp Med 2022 219:e20220131.
Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy. Woan KV, Kim H, Bjordahl R, Davis ZB, Gaidarova S, Goulding J, Hancock B, Mahmood S, Abujarour R, Wang H, Tuininga K, Zhang B, Wu CY, Kodal B, Khaw M, Bendzick L, Rogers P, Ge MQ, Bonello G, Meza M, Felices M, Huffman J, Dailey T, Lee TT, Walcheck B, Malmberg KJ, Blazar BR, Bryceson YT, Valamehr B, Miller JS, Cichocki F. Cell Stem Cell 2021 28:2062-2075.e5.
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. Science Immunology 2021 6:eabc9801.
- 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 137:2033-2045.
- 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*. Science Immunology 2018 3:eaat9781.
- 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.
- 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.
- CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin. Cheuk S, Schlums H, Gallais Sérézal I, Chiang SC, Martini E, Marquardt N, Gibbs A, Introini A, Forkel M, Almer S, Höög C, Tjernlund A, Michaelsson J, Folkersson L, Mjösberg J, Blomqvist L, Ehrström M, Ståhle M, Bryceson YT*, Eidsmo L*. Immunity 2017 46:287-300.
- Adaptive NK cells can persist in patients with GATA2 mutation depleted of stem and progenitor cells. Schlums H, Jung M, Han H, Theorell JT, Bigley V, Chiang SC, Davidson-Moncada JK, Dickinson R, Holmes TD, Hsu A, Townsley D, Winkler T, Aukrust P, Nordøy I, Holland SM, Collin M, Dunbar CE, Bryceson YT. Blood 2017 129:1927-1939.
- 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 SC, Komulainen-Ebrahim J, Rudberg Nilsson A, Ripperger T, Kokkonen H, Bryder D, Fioretos D, Henter JI, Möttönen M, Niinimäki R, Nilsson L, Pronk CJ, Qian H, Uusimaa J, Moilanen J, Tedgård U, Cammenga J, Bryceson YT. Blood 2017 129:2266-2279.
- VAMP8-dependent fusion of recycling endosomes with the plasma membrane facilitates T lymphocyte cytotoxicity. Marshall MR, HalimaniM, PattuV, Maier-PeuschelM, Müller ML, Becherer U, Hong W, HothM, Thomas TschernigT, Bryceson YT*, Rettig J*. J Cell Biol 2015 210:135-51.
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, Han H, Foley B, Mattsson K, Schaffer M, Larsson S, Ljunggren HG, Miller JS, Bryceson YT. Immunity 2015 42:443-56.