探花精选

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.

Photo of Yenan Bryceson's group

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 探花精选, 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.

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

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
  • Frank Cichocki, University of Minnesota
  • Cynthia Dunbar, National Institutes of Health
  • Stephan Ehl, University of Freiburg
  • Olov Ekwall, University of Gothenburg
  • Nelson Gekara, Stockholm University
  • Jan-Inge Henter, 探花精选
  • Jeffrey Klco, St Jude鈥檚 Hospital
  • Claudia Kutter, 探花精选 / SciLifeLab
  • Eric Long, National Institutes of Health
  • Jens Rettig, University of Saarland
  • Lars R枚nnblom, Uppsala University
  • Anna Wedell, 探花精选

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. 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.

Publications

Selected publications

  • Article: SCIENCE IMMUNOLOGY. 2023;8(82):eabn0484
    Helm EY; Zelenka T; Cismasiu VB; Islam S; Silvane L; Zitti B; Holmes TD; Drashansky TT; Kwiatkowski AJ; Tao C; Dean J; Obermayer AN; Chen X; Keselowsky BG; Zhang W; Huo Z; Zhou L; Sheridan BS; Conejo-Garcia JR; Shaw TI; Bryceson YT; Avram D
  • Article: JOURNAL OF EXPERIMENTAL MEDICINE (JEM). 2022;219(7):e20220202
    Campbell TM; Liu Z; Zhang Q; Moncada-Velez M; Covill LE; Zhang P; Darazam IA; Bastard P; Bizien L; Bucciol G; Enoksson SL; Jouanguy E; Karabela SN; Khan T; Kendir-Demirkol Y; Augusto Arias A; Mansouri D; Marits P; Marr N; Migeotte I; Moens L; Ozcelik T; Pellier I; Sendel A; Senoglu S; Shahrooei M; Smith CIE; Vandernoot I; Willekens K; Yasar KK; Bergman P; Abel L; Cobat A; Casanova J-L; Meyts I; Bryceson YT
  • Article: CELL STEM CELL. 2021;28(12):2062-2075.e5
    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 C-Y; 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
  • Article: BLOOD. 2021;137(15):2033-2045
    Kalinichenko A; Casoni GP; Dupre L; Trotta L; Huemer J; Galgano D; German Y; Haladik B; Pazmandi J; Thian M; Petronczki OY; Chiang SC; Taskinen M; Hekkala A; Kauppila S; Lindgren O; Tapiainen T; Kraakman MJ; Vettenranta K; Lomakin AJ; Saarela J; Seppanen MRJ; Bryceson YT; Boztug K
  • Article: SCIENCE IMMUNOLOGY. 2021;6(57):eabc9801
    Holmes TD; Pandey RV; Helm EY; Schlums H; Han H; Campbell TM; Drashansky TT; Chiang S; Wu C-Y; Tao C; Shoukier M; Tolosa E; Von Hardenberg S; Sun M; Klemann C; Marsh RA; Lau CM; Lin Y; Sun JC; Mansson R; Cichocki F; Avram D; Bryceson YT
  • Article: SCIENCE IMMUNOLOGY. 2018;3(29):eaat9781
    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
  • Article: JOURNAL OF EXPERIMENTAL MEDICINE (JEM). 2018;215(9):2379-2395
    Cichocki F; Wu C-Y; Zhang B; Felices M; Tesi B; Tuininga K; Dougherty P; Taras E; Hinderlie P; Blazar BR; Bryceson YT; Miller JS
  • Article: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2018;142(1):317-321.e8
    Tesi B; Rascon J; Chiang SCC; Burnyte B; Lofstedt A; Fasth A; Heizmann M; Juozapaite S; Kiudeliene R; Kvedaraite E; Miseviciene V; Muleviciene A; Mueller M-L; Nordenskjold M; Matuzeviciene R; Samaitiene R; Speckmann C; Stankeviciene S; Zekas V; Voss M; Ehl S; Vaiciene-Magistris N; Henter J-I; Meeths M; Bryceson YT
  • Article: BLOOD. 2017;129(16):2266-2279
    Tesi B; Davidsson J; Voss M; Rahikkala E; Holmes TD; Chiang SCC; Komulainen-Ebrahim J; Gorcenco S; Nilsson AR; Ripperger T; Kokkonen H; Bryder D; Fioretos T; Henter J-I; Mottonen M; Niinimaki R; Nilsson L; Pronk CJ; Puschmann A; Qian H; Uusimaa J; Moilanen J; Tedgard U; Cammenga J; Bryceson YT
  • Article: BLOOD. 2017;129(14):1927-1939
    Schlums H; Jung M; Han H; Theorell J; Bigley V; Chiang SCC; Allan DSJ; Davidson-Moncada JK; Dickinson RE; Holmes TD; Hsu AP; Townsley D; Winkler T; Wang W; Aukrust P; Nordoy I; Calvo KR; Holland SM; Collin M; Dunbar CE; Bryceson YT
  • Article: IMMUNITY. 2017;46(2):287-300
    Cheuk S; Schlums H; Serezal IG; Martini E; Chiang SC; Marquardt N; Gibbs A; Detlofsson E; Introini A; Forkel M; Hoog C; Tjernlund A; Michaelsson J; Folkersen L; Mjosberg J; Blomqvist L; Ehrstrom M; Stahle M; Bryceson YT; Eidsmo L
  • Article: JOURNAL OF CELL BIOLOGY. 2015;210(1):135-151
    Marshall MR; Pattu V; Halimani M; Maier-Peuschel M; M眉ller M-L; Becherer U; Hong W; Hoth M; Tschernig T; Bryceson YT; Rettig J
  • Article: IMMUNITY. 2015;42(3):443-456
    Schlums H; Cichocki F; Tesi B; Theorell J; Beziat V; Holmes TD; Han H; Chiang SCC; Foley B; Mattsson K; Larsson S; Schaffer M; Malmberg K-J; Ljunggren H-G; Miller JS; Bryceson YT

Funding

  • Swedish Research Council
  • Wallenberg Foundation (Wallenberg Academy Fellow)
  • Swedish Cancer Foundation
  • Center for Innovative Medicine
  • 探花精选 Research Foundation

Staff and contact

Group leader

All members of the group