Lisa Westerberg Group
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.
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
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
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)
Sven Petersen, PhD, 2011-2012
Carin Dahlberg, PhD, 2010-2015
Marisa Baptista, PhD, 2009-2014
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
- 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
- University of Milan, Italy: Dr. Anna Villa
- Stockholm University, Sweden: Dr. Eva Severinson
- Karolinska Institutet, Sweden: Drs. Mikael Karlsson, John Andersson, Liv Eidsmo, Susanne Nylén, Klas Kärre, Magnus Björkholm, Hans-Erik Claesson, Lena Ström, Evren Alici, Robert Månsson, and Ola Winqvist
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
Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells.
Nat Commun 2016 Jul;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
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