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
Yenan Bryceson, Group Leader, PhD, Assistant Professor
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 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
Hongya Han, PhD
Hongya received his MSc degree from the Beijing Jiaotong University, China in 2009, and his PhD from Karolinska Institutet in 2014. He is continuing work in Bryceson lab as a postdoc focusing on epigenetic regulation in NK cell development. Hongya is currently optimising the CRISPR/Cas9 system in CD34+ HSCs to study the function of certain transcription factors in late NK cell development. He enjoys playing badminton, finishing, hiking, cooking and making traditional Chinese painting in his free time.
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.
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.
Matthias Voss, PhD
Matthias received his MSc degree in biochemistry and molecular biology from the Christian-Albrechts University in Kiel, Germany, in 2009 and a PhD (summa cum laude) in biochemistry from the Ludwig-Maximilians University in Munich, Germany, in 2014. He joined the Bryceson lab in 2015 and will adopt genome editing technologies to interrogate the molecular mechanisms underlying lymphocyte cytotoxicity. He is currently supported by a postdoctoral fellowship from the Wenner-Gren Foundations. In his spare time, Matthias enjoys running and swimming.
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.
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.
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!
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
Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function.
Immunity 2015 Mar;42(3):443-56.
VAMP8-dependent fusion of recycling endosomes with the plasma membrane facilitates T lymphocyte cytotoxicity.
J. Cell Biol. 2015 Jul;210(1):135-51.
Hemophagocytic lymphohistiocytosis in 2 patients with underlying IFN-γ receptor deficiency.
J. Allergy Clin. Immunol. 2015 Jun;135(6):1638-41.
Combined newborn screening for familial hemophagocytic lymphohistiocytosis and severe T- and B-cell immunodeficiencies.
J. Allergy Clin. Immunol. 2014 Jul;134(1):226-8.
Pathophysiology and spectrum of diseases caused by defects in lymphocyte cytotoxicity.
Exp. Cell Res. 2014 Jul;325(1):10-7.
NK cell development and function--plasticity and redundancy unleashed.
Semin. Immunol. 2014 Apr;26(2):114-26.
The evolution of cellular deficiency in GATA2 mutation.
Blood 2014 Feb;123(6):863-74.
Immunomodulatory activity of commonly used drugs on Fc-receptor-mediated human natural killer cell activation.
Cancer Immunol. Immunother. 2014 Jun;63(6):627-41.
Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage.
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.
Blood 2013 Feb;121(8):1345-56.
A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes.
Blood 2012 Mar;119(12):2754-63.
Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D.
Blood 2011 Nov;118(22):5783-93.
ORAI1-mediated calcium influx is required for human cytotoxic lymphocyte degranulation and target cell lysis.
Proc. Natl. Acad. Sci. U.S.A. 2011 Feb;108(8):3324-9.
Cytotoxic therapy for severe swine flu A/H1N1.
Lancet 2010 Dec;376(9758):2116.
Functional analysis of human NK cells by flow cytometry.
Methods Mol. Biol. 2010 ;612():335-52.
Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2.
Blood 2010 Oct;116(15):2635-43.
Synergistic signals for natural cytotoxicity are required to overcome inhibition by c-Cbl ubiquitin ligase.
Immunity 2010 Feb;32(2):175-86.
Regulation of human NK-cell cytokine and chemokine production by target cell recognition.
Blood 2010 Mar;115(11):2167-76.
Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.
Blood 2009 Sep;114(13):2657-66.
Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses.
Immunity 2009 Jul;31(1):99-109.