Yenan Bryceson group
Subsets of lymphocytes, such as cytotoxic T cells and natural killer (NK) cells, can kill infected or neoplastic cells. Individuals carrying mutations in specific genes required for such lymphocyte cytotoxicity may develop life-threatening disorders.
In the most severe cases, these are often triggered by viral infections and elicit uncontrolled immune cell proliferation and hyperinflammatory immune pathology. Otherwise, such mutations may predispose to malignancies.
We have developed methods for quantification of human cytotoxic lymphocyte responses. Our research strives to understand the complex regulation of cytotoxic lymphocyte function in health, infection, and disease in the setting of human genetic variability and environmental factors. Moreover, we aim to develop refined techniques for determining human immune status. We hope that outcomes of this work will include fundamentally new conceptualizations of immunological disorders, basic immunological and genetic insights, and potent, specific immunomodulatory 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, hemophagocytic lymphohistiocytosis
Yenan BrycesonProfessor, 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 ZendeganiBiomedical 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 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 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 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 SchlumsPhD 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 RagaPhD 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 CasoniPhD 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.
Current projects in the group encompass studies of cytotoxic lymphocyte signaling and activation, specifically focusing on the mechanisms of granule release, development of improved assays for identification of human immunodeficiencies affecting cytotoxic lymphocyte function, studies of primary immunodeficiencies with high mortality or morbidity related to viral infections, autoimmunity, and cancer, as well as projects aimed at understanding the variability among humans in regards to cytotoxic lymphocyte responses.
These projects employ advanced tools in molecular biology, flow cytometry, microscopy and high-throughput genetics.
Research is performed with a number of national and international collaborators:
- Matthew Collin, Newcastle University
- Stephan Ehl, University of Freiburg
- Kimberley Gilmour, Great Ormond Street Hospital
- Jan-Inge Henter, Karolinska Institutet
- Eric Long, National Institutes of Health
- Jeffrey Miller, University of Minnesota
- Magnus Nordenskjöld, Karolinska Institutet
- Jens Rettig, University of Saarland
- Lars Rönnblom, Uppsala University
- Anna Wedell, Karolinska Institutet
- Sheila Weitzmann, SickKids Hospital
- European Research Council (Starting Grant)
- Swedish Research Council
- Swedish Foundation for Strategic Research
- Wallenberg Foundation (Wallenberg Academy Fellow)
- Swedish Cancer Foundation
- Histiocytosis Association
- Karolinska Institutet Research Foundation
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
Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study.
Löfstedt A, Chiang SC, Onelöv E, Bryceson YT, Meeths M, Henter JI
Lancet Haematol 2015 Dec;2(12):e536-42
Chediak-Higashi syndrome: Lysosomal trafficking regulator domains regulate exocytosis of lytic granules but not cytokine secretion by natural killer cells.
Gil-Krzewska A, Wood SM, Murakami Y, Nguyen V, Chiang SCC, Cullinane AR, et al
J. Allergy Clin. Immunol. 2016 Apr;137(4):1165-1177
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
Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3.
Haapaniemi EM, Kaustio M, Rajala HL, van Adrichem AJ, Kainulainen L, Glumoff V, et al
Blood 2015 Jan;125(4):639-48
Pathophysiology and spectrum of diseases caused by defects in lymphocyte cytotoxicity.
Meeths M, Chiang SC, Löfstedt A, Müller ML, Tesi B, Henter JI, et al
Exp. Cell Res. 2014 Jul;325(1):10-7
The evolution of cellular deficiency in GATA2 mutation.
Dickinson RE, Milne P, Jardine L, Zandi S, Swierczek SI, McGovern N, et al
Blood 2014 Feb;123(6):863-74
Transcriptional regulation of Munc13-4 expression in cytotoxic lymphocytes is disrupted by an intronic mutation associated with a primary immunodeficiency.
Cichocki F, Schlums H, Li H, Stache V, Holmes T, Lenvik TR, et al
J. Exp. Med. 2014 Jun;211(6):1079-91
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage.
Cohnen A, Chiang SC, Stojanovic A, Schmidt H, Claus M, Saftig P, et al
Blood 2013 Aug;122(8):1411-8
Comparison of primary human cytotoxic T-cell and natural killer cell responses reveal similar molecular requirements for lytic granule exocytosis but differences in cytokine production.
Chiang SC, Theorell J, Entesarian M, Meeths M, Mastafa M, Al-Herz W, et al
Blood 2013 Feb;121(8):1345-56
A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes.
Bryceson YT, Pende D, Maul-Pavicic A, Gilmour KC, Ufheil H, Vraetz T, et al
Blood 2012 Mar;119(12):2754-63
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
ORAI1-mediated calcium influx is required for human cytotoxic lymphocyte degranulation and target cell lysis.
Maul-Pavicic A, Chiang SC, Rensing-Ehl A, Jessen B, Fauriat C, Wood SM, et al
Proc. Natl. Acad. Sci. U.S.A. 2011 Feb;108(8):3324-9
Cytotoxic therapy for severe swine flu A/H1N1.
Henter JI, Palmkvist-Kaijser K, Holzgraefe B, Bryceson YT, Palmér K
Lancet 2010 Dec;376(9758):2116
Functional analysis of human NK cells by flow cytometry.
Bryceson YT, Fauriat C, Nunes JM, Wood SM, Björkström NK, Long EO, et al
Methods Mol. Biol. 2010 ;612():335-52
Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2.
Meeths M, Entesarian M, Al-Herz W, Chiang SC, Wood SM, Al-Ateeqi W, et al
Blood 2010 Oct;116(15):2635-43
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
Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity.
Wood SM, Meeths M, Chiang SC, Bechensteen AG, Boelens JJ, Heilmann C, et al
Blood 2009 Nov;114(19):4117-27
We are seeking a highly motivated postdoctoral fellow to work full time on a project investigating how cytotoxic lymphocytes, such as NK cells and cytotoxic T cells, 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.
This post-doctoral position was created to stimulate basic research on signalling and vesicle trafficking in cytotoxic lymphocytes. The research aims to gain understanding of the molecular mechanisms of lymphocyte cytotoxic function and facilitate clinical diagnostic efforts. 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, Cell Biology, or Biochemistry with publications in internationally renowned peer-reviewed journals. Less than 3 years postdoctorial 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 microscopy, flow cytometry, cell culture, gene knockdown, and/or proteomics is an advantage.
To apply, submit Cover letter and CV, including publication list and names of three references to Yenan Bryceson.