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

Members

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 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.

Phone: +46 (0)704 43 1944

 

Jelve Zendegani

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!

 

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.

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 currently holds an EMBO long-term fellowship (2016 & 2017) and was previously supported by a fellowship awarded by the Wenner-Gren foundations.

Irene Gutierrez Perez, PhD

Irene received her MSc degree in chemistry from University of Alicante, Spain, in 2010 and a PhD (summa cum laude with international mention) in Neuroscience from the Institute of Neuroscience in Alicante, Spain, in 2015. She joined the Bryceson lab in 2017 and her work focuses on understanding and harnessing NK cell memory. She currently holds a fellowship awarded by the Wenner-Gren Foundations. In her spare time she enjoys reading, doing sports and traveling. 

Donatella Galgano, PhD

Donatella received her PhD in Biochemistry and Molecular Biology from University of Siena, Italy in 2015. She joined the Bryceson lab in 2017. Her work focuses on vesicular traffic pathways underlying lymphocyte cytotoxicity and their alteration in the context of primary immunodeficiencies. In her spare time she enjoys reading and listening to rock music, going to the gym and doing yoga.

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.

Angel Visozo, PhD

Angel received his MSc degree in biochemistry and molecular biology from the University of A Coruña, Spain, in 2010, a MSc degree in bioinformatics from the UNIA, Spain, in 2011, and a PhD (summa cum laude) in biochemistry from the the University of A Coruña, Spain, in 2015. Co-supervised by Adnane Achour at SciLifeLab, he has been affiliated with the Bryceson lab since 2017. His research is focused on the structural and biochemical description of different protein alterations related to human cytotoxic lymphocyte signaling. In his spare time he enjoys cooking and learning photography.

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.

Takuya Sekine, PhD

Tak received his PhD in Clinical Medicine Research from Imperial College London, UK in 2016 and joined the Bryceson lab in 2017. His work focuses on identifying and mechanistically understanding novel primary immunodeficiency diseases with susceptibility to viral infection, hyperinflammation, as well as cancer. In his spare time he enjoys watching movies, swimming and discovering nice coffee places.

Samuel Chiang, PhD

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 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.

Bianca Tesi, MD, PhD student

Bianca received her Medical Doctor degree from the University of Florence, Italy in 2011. She is currently enrolled as a PhD student at Karolinska Institutet. Her work focuses on identifying genetic factors causing severe primary immunodeficiency syndromes and predisposition to infectious diseases, cancer and autoimmunity. When free, she relaxes with family, good food, movies and walks by the lake.

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.

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)

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 S, Marquardt N, et al
Immunity 2017 Feb;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 S, et al
Blood 2017 Apr;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 T, Chiang S, et al
Blood 2017 Apr;129(16):2266-2279.

Acquired somatic mutations in PNH reveal long-term maintenance of adaptive NK cells independent of HSPCs.
Corat M, Schlums H, Wu C, Theorell J, Espinoza D, Sellers S, et al
Blood 2017 Apr;129(14):1940-1946.

Natural killer cell memory in context.
Holmes T, Bryceson Y
Semin. Immunol. 2016 Aug;28(4):368-76.

Epigenetic Regulation of Adaptive NK Cell Diversification.
Tesi B, Schlums H, Cichocki F, Bryceson Y
Trends Immunol. 2016 Jul;37(7):451-61.

Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study.
Löfstedt A, Chiang S, Onelöv E, Bryceson Y, Meeths M, Henter J
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 S, Murakami Y, Nguyen V, Chiang S, Cullinane A, et al
J. Allergy Clin. Immunol. 2016 Apr;137(4):1165-77.

CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT.
Cichocki F, Cooley S, Davis Z, DeFor T, 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 T, et al
Immunity 2015 Mar;42(3):443-56.  

VAMP8-dependent fusion of recycling endosomes with the plasma membrane facilitates T lymphocyte cytotoxicity.
Marshall M, Pattu V, Halimani M, Maier-Peuschel M, Müller M, 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 A, 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 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.

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.

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.

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 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.

Hematology