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 Infectious Medicine and employs a wide range of techniques including multiparameter flow cytometry, confocal microscopy, live-cell imaging, next-generation sequencing, and biochemical 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

Members

Yenan Bryceson, Group Leader, PhD, Assistant Professor

Yenan received his Masters 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 Infectious Medicine at Karolinska University Hospital Huddinge. In his spare time he enjoys hiking, skiing, fly fishing and is trying to figure out surfing.

Phone: +46 (0)704 43 1944

Stephanie Wood, PhD

Stephanie received her BSc (Honours) degree from the University of Queensland, Australia in 2004, and her PhD from the same University in 2009. She is continuing work in the Bryceson lab investigating how proteins required for lytic granule-mediated killing regulate trafficking and membrane fusion in cytotoxic lymphocytes. In her spare time she enjoys playing netball, orienteering, skiing and traveling.

Phone: +46 8 585 82283

Samuel Chiang, PhD student

Sam received his Masters degree from the National University of Singapore, Singapore in 2008. He is currently enrolled in the Experimental Medicine Program at Karolinska Institutet. His work focuses on understanding the pathogenesis and mechanisms of immunodeficiency syndromes affecting lymphocyte cytotoxicity. He is currently optimizing a novel method of tricking himself to go to the gym. Results are not very forthcoming.

Jakob Theorell, MD PhD student

Jakob started his medical training at Karolinska Institutet in 2007. He is currently enrolled in the MD-PhD Program at Karolinska Institutet. His work focuses on understanding the mechanisms of disease in patients suffering from chronic immunodeficiency syndromes. In his spare time he enjoys playing music of various genres on the double bass and being in the forest.

Heinrich Schlums, PhD student

Heinrich received his Masters 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.

Martha-Lena Müller, PhD student

Martha-Lena received her Master´s degree from the Ruprecht-Karls University in Heidelberg in 2011. She is enrolled in the Experimental Medicine Program at Karolinska Institutet. Her research addresses the spatio-temporal dynamics, interactions, and function of proteins associated with fatal immunodeficiency syndromes and required for cytotoxic lymphocyte exocytosis. In her free time she enjoys long walks at the seaside and, giving unequaled pleasure to her neighbors, she likes singing.

Projects

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

Financial support

  • European Research Council (Starting Grant) 
  • Swedish Research Council 
  • Swedish Foundation for Strategic Research 
  • Wallenberg Foundation (Wallenberg Academy Fellow) 
  • Swedish Cancer Foundation 
  • Histiocytosis Association 
  • CIMED 
  • ALF 
  • Karolinska Institutet Research Foundation

Selected publications

Link to all publications (PubMed)

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

Functional anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies in patients with systemic lupus erythematosus.
Hagberg N, Theorell J, Hjorton K, Spee P, Eloranta M, Bryceson Y, et al
2015 Apr;67(4):1000-11

Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3.
Haapaniemi E, Kaustio M, Rajala H, van Adrichem A, Kainulainen L, Glumoff V, et al
Blood 2015 Jan;125(4):639-48

Combined newborn screening for familial hemophagocytic lymphohistiocytosis and severe T- and B-cell immunodeficiencies.
Borte S, Meeths M, Liebscher I, Krist K, Nordenskjöld M, Hammarström L, et al
J. Allergy Clin. Immunol. 2014 Jul;134(1):226-8

Pathophysiology and spectrum of diseases caused by defects in lymphocyte cytotoxicity.
Meeths M, Chiang S, Löfstedt A, Müller M, Tesi B, Henter J, et al
Exp. Cell Res. 2014 Jul;325(1):10-7

NK cell development and function--plasticity and redundancy unleashed.
Cichocki F, Sitnicka E, Bryceson Y
Semin. Immunol. 2014 Apr;26(2):114-26

The evolution of cellular deficiency in GATA2 mutation.
Dickinson R, Milne P, Jardine L, Zandi S, Swierczek S, 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 T, et al
J. Exp. Med. 2014 Jun;211(6):1079-91

Immunomodulatory activity of commonly used drugs on Fc-receptor-mediated human natural killer cell activation.
Theorell J, Gustavsson A, Tesi B, Sigmundsson K, Ljunggren H, Lundbäck T, et al
Cancer Immunol. Immunother. 2014 Jun;63(6):627-41

Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage.
Cohnen A, Chiang S, 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 S, 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 Y, Pende D, Maul-Pavicic A, Gilmour K, 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 S, Wood S, 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 S, Rensing-Ehl A, Jessen B, Fauriat C, Wood S, et al
Proc. Natl. Acad. Sci. U.S.A. 2011 Feb;108(8):3324-9

Cytotoxic therapy for severe swine flu A/H1N1.
Henter J, Palmkvist-Kaijser K, Holzgraefe B, Bryceson Y, Palmér K
Lancet 2010 Dec;376(9758):2116

Functional analysis of human NK cells by flow cytometry.
Bryceson Y, Fauriat C, Nunes J, Wood S, Björkström N, Long E, 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 S, Wood S, 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 H, Das A, Gross C, Bryceson Y, Long E
Immunity 2010 Feb;32(2):175-86

Regulation of human NK-cell cytokine and chemokine production by target cell recognition.
Fauriat C, Long E, Ljunggren H, Bryceson Y
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 S, Meeths M, Chiang S, Bechensteen A, Boelens J, Heilmann C, et al
Blood 2009 Nov;114(19):4117-27

Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.
Bryceson Y, Ljunggren H, Long E
Blood 2009 Sep;114(13):2657-66

Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
Liu D, Bryceson Y, Meckel T, Vasiliver-Shamis G, Dustin M, Long E
Immunity 2009 Jul;31(1):99-109

Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients.
Bryceson Y, Rudd E, Zheng C, Edner J, Ma D, Wood S, et al
Blood 2007 Sep;110(6):1906-15

Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion.
Bryceson Y, March M, Ljunggren H, Long E
Blood 2006 Jan;107(1):159-66

Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells.
Bryceson Y, March M, Barber D, Ljunggren H, Long E
J. Exp. Med. 2005 Oct;202(7):1001-12

Open positions

  • Postdoc position

    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 Infectious 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.

Infectious Disease Medicine