Yenan Bryceson group

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.

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.

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.

Our laboratory is based at the Center for Hematology and Regenerative Medicine 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.

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

Photo: HERM

Members

Yenan Bryceson

Professor, Group Leader, PhD

Yenan received his MSc degree from the University of Oslo, Norway in 2000, and 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 and receiving support from the National Institutes of Health, Karolinska Institutet Graduate Partnership Program. He is Assistant Professor. His laboratory is located within the Center for Hematology and Regenerative Medicine at Karolinska University Hospital Huddinge. In his spare time he enjoys hiking, skiing, fly fishing and is trying to figure out surfing.

Jelve Zendegani

Biomedical scientist

Jelve trained 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. She joined the Bryceson lab in 2014 where she performs analyses of patients with suspected immunodeficiencies, in addition to supporting the every-day function of the laboratory. In her spare time she enjoys baking, photography, travelling and hiking.

Tim Holmes

PhD

Tim 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!

Saeed Eshtad

PhD

Saeed received his MSc degree in Molecular Life Sciences from Stockholm University, Sweden in 2012. He started his PhD studies in Helleday lab, Karolinska Institutet, and defended his thesis with the title of “Targeting DNA Repair Pathways for Cancer Therapy” in 2017. He is currently interested in studying the pathophysiology of MDS and AML using CRISPR/Cas9 genome editing. Saeed enjoys playing indoor football and calligraphy in his free time.

Beatrice Zitti

PhD

Beatrice received her MSc degree in Medical Biotechnology in 2013 and her PhD (with honours) in Life Science in 2016, from University of Rome – Sapienza, Italy, after working as a Guest Researcher in the lab of John J. O’Shea at the NIH. She joined the Bryceson lab in 2017. Her work will address mechanisms of activation and maintenance of memory cytotoxic lymphocytes in health and disease. In her spare time she enjoys travelling, good music and doing sports.

Heinrich Schlums

PhD student

Heinrich received his MSc degree from the Technical Universtiy of Braunschweig, Germany in 2010. He is currently enrolled in the Experimental Medicine Program at Karolinska Institutet. His studies concern human cytotoxic lymphocyte signalling in health and disease. In his spare time he enjoys picking mushrooms and tasting wine.

Lamberto Torralba Raga

PhD student

Lamberto Torralba Raga received his BSc degree in Biochemistry in 2012 from the University of Valencia, Spain. He then moved to Stockholm to pursue an MSc degree in Biomedicine at Karolinska Institutet, Sweden, which he finished in 2014. He is currently enrolled in the Experimental Medicine PhD Program at Karolinska Institutet. His research addresses the immunoregulation of cytotoxic lymphocytes in severe systemic autoimmunity. In his spare time he enjoys reading science fiction, going out for a run and traveling.

Giovanna Perinetti Casoni

PhD student

Giovanna received her BSc in Biotechnology in 2013 from the University of Trieste, Italy. Then, 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 Covill

PhD Student

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 PhD in the Bryceson lab in 2019, and 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

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 is performed with a number of national and international collaborators:

  • 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

Financial 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)

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):

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;():

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

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):

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

HLH: genomics illuminates pathophysiological diversity.
Tesi B, Bryceson YT
Blood 2018 07;132(1):5-7

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

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 al
Immunity 2017 02;46(2):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 J, Bigley V, Chiang SC, et al
Blood 2017 04;129(14):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 SCC, et al
Blood 2017 04;129(16):2266-2279

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 al
Blood 2017 04;129(14):1940-1946

Natural killer cell memory in context.
Holmes TD, Bryceson YT
Semin. Immunol. 2016 08;28(4):368-76

Epigenetic Regulation of Adaptive NK Cell Diversification.
Tesi B, Schlums H, Cichocki F, Bryceson YT
Trends Immunol. 2016 07;37(7):451-461

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 al
Leukemia 2016 Feb;30(2):456-63

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 al
Immunity 2015 Mar;42(3):443-56

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 al
J. Cell Biol. 2015 Jul;210(1):135-51

Hemophagocytic lymphohistiocytosis in 2 patients with underlying IFN-γ receptor deficiency.
Tesi B, Sieni E, Neves C, Romano F, Cetica V, Cordeiro AI, et al
J. Allergy Clin. Immunol. 2015 Jun;135(6):1638-41

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 al
Blood 2011 Nov;118(22):5783-93

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

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

Postdoc position

We are seeking highly motivated postdoctoral fellows to work full time on projects investigating how cytotoxic lymphocytes, such as NK cells and cytotoxic T cells, differentiate and kill target cells.

We offer a unique setting for translational research aimed at understanding causes of pathogenesis in human diseases associated with primary defects in cytotoxic lymphocyte function. The Center for Hematology and Regenerative Medicine is situated at the Karolinska University Hospital Huddinge with reliable access to human material, including patient samples. Translational research efforts are encouraged. Successful candidates will be encouraged to pursue their own fundamental research questions and to publish important results in leading journals.

Requirements include a Ph.D. and/or M.D. within the fields of Immunology, Genetics, Biochemistry, or Cell Biology with publications in internationally renowned peer-reviewed journals. Less than 3 years postdoctoral training and demonstrated communication skills in English. The ideal candidates will have extensive training in immunology, molecular biology, cell biology, biochemistry and/or bioinformatics. Experience with flow cytometry, cell culture, genome editing, proteomic or advanced imaging is an advantage.

To apply, submit Cover letter and CV, including publication list and names of three references to Yenan Bryceson.