Lisa Westerberg Group
Immunodeficiency Diseases
Primary immunodeficiencies are diseases in which part of the body's immune system is missing or does not function properly. Most primary immunodeficiencies are genetic disorders and the majority are diagnosed in children under the age of one. Translational studies of primary immunodeficiency diseases in patients and gene-targeted experimental models have increased our understanding of the cause for disease and led to development of new therapeutic approaches, including bone marrow transplantation and gene therapy. Understanding primary immunodeficiency diseases has also increased our knowledge of critical mechanisms for correct function of the immune system.OK
Our laboratory has focused on primary immunodeficiency caused by mutations in the Wiskott-Aldrich syndrome protein (WASP). WASP is uniquely expressed in cells of the immune system and coordinates cell surface signaling to changes in the actin cytoskeleton, thereby regulating cell movement, cell-to-cell communication, and intracellular signaling. The clinical outcome of WASP-associated primary immunodeficiency depends on how the mutations affect WASP expression and activity. Mutations that abolish expression of WASP leads to broad dysfunction of the immune system and patients develop eczema, autoimmunity and tumors. Mutations that induce constitutively-active WASP lead to development of severe neutropenia and recurrent bacterial infections. It remains largely unknown how different mutations of WASP can elicit such diverse effects on the immune system. To delineate these strikingly different clinical phenotypes, our laboratory is utilizing patient samples and gene-targeted models. Specifically, we are investigating the role of WASP family proteins, their interacting partners, and the actin cytoskeleton for regulation of allergy, autoimmunity, and cancer. Moreover, we are utilizing our experimental models to test new treatment strategies for primary immunodeficiency diseases.
The overall goal of our research is to increase the understanding of WASP family proteins and their role in immunodeficiency. We expect to reveal critical mechanisms for maintenance of a correctly regulated immune system in health and disease
Group Members
PhD, Associate Professor Lisa Westerberg
Lisa Westerberg graduated from Stockholm University with a M.Sc. in Molecular Biology and received her Ph.D. in Cell and Molecular Biology in 2003 from Karolinska Institutet where she studied under Professor Eva Severinson. In 2009 she completed her postdoctoral research at Harvard Medical School in the laboratories of Professors Scott Snapper and Luigi Notarangelo. She joined the faculty at Department of Medicine at Karolinska Institutet, Stockholm in 2009 after receiving an Assistant Professor position appointed by the Swedish Research Council. In 2013, Dr Westerberg joined the faculty at Department of Microbiology Tumor and Cell biology as senior researcher and group leader. Dr Westerberg is the treasurer of the Swedish Society for Immunology and coordinates the WASPSTINGS network funded by STINT. Dr Westerberg is a Ragnar Söderberg fellow in Medicine.
Fax: +46 8 524 87150
Address: MTC, Box 280, Nobels väg 16 Karolinska Institutet S-171 77 Stockholm, SWEDEN
 | Zhoujie Ding | Postdoc | |
 | Minghui He | Postdoc | |
 | Marton Keszei | Associated | |
 | Nikolai Kouznetsov | Senior lab manager | |
 | Mariana Oliveira | PhD student, Graduate Student | |
 | Julien Record | Postdoc | |
 | Anton Sendel | PhD student, Graduate Student | |
 | Meike Thiemann | Associated | |
 | Magda-Liz Torres Garcia | Graduate Student | |
 | Larissa Vasconcelos Fontes | Associated | |
 | Lisa Westerberg | Senior researcher | |
 | Qintong Zhang | Associated |
PhD students
Giovanna Perinetti Casoni, PhD student, Karolinska Institutet (main supervisor: Yenan Bryceson)
Silke Sohn, MSc, PhD student, Karolinska Institutet (main supervisor: Mikael Karlsson)
Lucia Sereni, MSc, PhD student, Milan University (main supervisor: Anna Villa)
Alumni
Postdocs
Hanna Brauner, MD PhD, 2016-2018
Sven Petersen, PhD, 2011-2012
PhD students
Joanna Kritikou, PhD, 2012-2017
Carin Dahlberg, PhD, 2010-2015
Marisa Baptista, PhD, 2009-2014
Master and Undergraduate students
Chiara Geyer, Erasmus student 2017
Lena Bohaumilitzky, Erasmus student 2017
Stamatina Rentouli, Erasmus student 2016-2017
Elena Griseti, Master student 2017
Alexander Schäffer, Master student 2017
Deborah Sandfort, Bachelor student 2016-2017
Hannah Wurzer, Master student 2016
Marissa Franke, Euroscholar student 2016
Laura Köcher, student 2015-2016
Pei Yee Tey, Amgen Scholar student 2016
Jaime James, Master student and Research assistant 2014-2016
Paul Drescher, Bachelor student 2014-2015
Wenqing Yan, Amgen scholar student 2015
Yi Fei Lee, Amgen scholar student 2015
Bettina Mwale, Amgen Scholar student 2014
Katharina Koch, student 2012
Lucy Garner, Amgen Scholar student 2012
Bisera Stepanovska, Amgen Scholar student 2012
Rhea Chatterjea, Amgen Scholar student 2011
Chiao Yin Lim, Amgen Scholar student 2011
Katherine Oliver, Amgen Scholar student 2010
Collaborators
- Harvard Medical School, USA: Drs. Scott Snapper, Luigi Notarangelo, and Jolan Walter
- Baylor College of Medicine, USA: Dr. Jordan Orange
- University of Maryland, USA: Dr. Wenxia Song
- University College London, UK: Drs. Adrian Thrasher and Siobhan Burns
- Leuven University Hospital, Belgium: Dr. Peter Vandenberghe
- University of Milan, Italy: Dr. Anna Villa
- New York University Abu Dhabi: Dr Piergiorgio Percipalle
- Huazhong University of Science and Technology, China: Dr. Chaohong Liu
- Chongqing Medical University, China: Dr. Xiaodong Zhao
- Umeå University, Sweden: Dr Mattias Forsell
- Stockholm University, Sweden: Dr. Eva Severinson
- Karolinska Institutet, Sweden: Drs. Mikael Karlsson, John Andersson, Liv Eidsmo, Susanne Nylén, Fredrik Wermeling, Klas Kärre, Magnus Björkholm, Hans-Erik Claesson, Lena Ström, Evren Alici, Robert Månsson, and Ola Winqvist
Funding
We gratefully acknowledge the funding from:
• Childhood Cancer Foundation
• Center for Allergy Research
• Clas Groschinsky Foundation
• European Commission 7th framework program
• Fundação para e a Ciência e Tecnologia
• Jeansson Foundation
• Karolinska Institutet foundations
• Konung Gustaf V:s 80-årsfond
• Magnus Bergvall Foundation
• Olle Engkvist Byggmästare foundation
• Ragnar Söderberg foundation
• Swedish Cancer Society
• Swedish Foundation for International cooperation in research and higher education
• Swedish Medical Society
• Swedish Society for Medical Research (SSMF)
• Swedish Research Council
• Åke Olsson foundation
• Åke Wiberg Foundation
For Science and Education
Our group is also actively involved in medical education and our research is featured on several external research websites
Ragnar Söderberg blogg and movie
Interview about mentorship at the Amgen scholar website
Publications
Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive.
J. Clin. Invest. 2018 Aug;128(9):4115-4131
Wiskott-Aldrich syndrome gene mutations modulate cancer susceptibility in the p53+/- murine model
Keszei M, Kritikou JS, He M, Oliveira M, Sandfort D, Wurzer H, Kuiper K, Westerberg LS
OncoImmunology 2018. In press
Alternative Splicing of Controls Regulatory T Cell Effector Functions and Is Associated With Human Atherosclerotic Plaque Stability.
Circ. Res. 2018 May;122(10):1385-1394
Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo.
Sci Rep 2018 01;8(1):154
Nuclear Wiskott-Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells.
Genome Med 2017 10;9(1):91
The Small Rho GTPases Rac1 and Rac2 Are Important for T-Cell Independent Antigen Responses and for Suppressing Switching to IgG2b in Mice.
Front Immunol 2017 ;8():1264
Wiskott-Aldrich syndrome protein regulates autophagy and inflammasome activity in innate immune cells.
Nat Commun 2017 11;8(1):1576
Defective thymic output in WAS patients is associated with abnormal actin organization.
Sci Rep 2017 Sep;7(1):11978
Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.
PLoS Biol. 2017 Aug;15(8):e2001750
H1N1 vaccination in Sjögren's syndrome triggers polyclonal B cell activation and promotes autoantibody production.
Ann. Rheum. Dis. 2017 Oct;76(10):1755-1763
Interferon γ is a STAT1-dependent direct inducer of BCL6 expression in imatinib-treated chronic myeloid leukemia cells.
Oncogene 2017 08;36(32):4619-4628
Deletion of Dock10 in B Cells Results in Normal Development but a Mild Deficiency upon and Stimulations.
Front Immunol 2017 ;8():491
Activation of compensatory pathways via Rac2 in the absence of the Cdc42 effector Wiskott-Aldrich syndrome protein in Dendritic cells.
Small GTPases 2017 Jan;():1-8
Human 15-lipoxygenase-1 is a regulator of dendritic-cell spreading and podosome formation.
FASEB J. 2017 02;31(2):491-504
IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo.
Sci Rep 2016 08;6():30636
Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells.
Nat Commun 2016 07;7():12175
N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome.
Blood 2016 Jan;127(2):216-20
Foxp3 lacking exons 2 and 7 is unable to confer suppressive ability to regulatory T cells in vivo.
J. Autoimmun. 2015 Sep;63():23-30
Deletion of WASp and N-WASp in B cells cripples the germinal center response and results in production of IgM autoantibodies.
J. Autoimmun. 2015 Aug;62():81-92
The Rho GTPase Cdc42 Is Essential for the Activation and Function of Mature B Cells.
J. Immunol. 2015 May;194(10):4750-8
A novel mouse model for the hyper-IgM syndrome: a spontaneous activation-induced cytidine deaminase mutation leading to complete loss of Ig class switching and reduced somatic hypermutation.
J. Immunol. 2014 Nov;193(9):4732-8
Unraveling the repertoire in wiskott-Aldrich syndrome.
Front Immunol 2014 ;5():539
Congenital defects in neutrophil dynamics.
J Immunol Res 2014 ;2014():303782
N-wasp is essential for the negative regulation of B cell receptor signaling.
PLoS Biol. 2013 Nov;11(11):e1001704
Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function.
Blood 2012 Apr;119(17):3966-74
B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice.
Blood 2012 Mar;119(12):2819-28
Buzz in the dendritic cell synapse.
Blood 2011 Sep;118(9):2381-2
Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes.
J. Exp. Med. 2010 Jun;207(6):1145-52
Link to all Lisa Westerberg Publications on PubMed