Immunology: Jannie Borst
Jannie Borst, Ph.D. professorHead of Division, Group Leader
- +31 20 512 2056
- Jannie Borst
Research interest: Deciphering molecular mechanisms that govern the T cell response
Our work is in the first place inspired by the desire to improve immunotherapy of cancer. Sustaining survival and memory function of T cells is expected to improve anti-tumor immunity. At the same time, mechanisms we elucidate may be exploited to improve vaccination against infectious disease and to block undesired immune responses, as in auto-immunity and transplant rejection. This work is carried out in vivo in mouse models and in matching cellular systemsin vitro, whereby we presently focus on interactions between T cells and dendritic cells. We collaborate with biotech industry to validate therapeutic antibodies. A second aim is to explore the concept of "immunogenic cell death" in the context of radio- or chemo-immunotherapy. In this work, we combine our expertise on T cell- and dendritic cell function with our expertise on apoptosis signaling. This work is done for a large part in cell modelsin vitro, using biochemical and cell biological approaches. The link between basic cell biology and clinical practice is made by studies in mouse tumor models. In this translational work, we collaborate with the Division of Radiotherapy.
● Discovery of the CD3 gamma, delta and epsilon subunits of the human T cell receptor/CD3 complex.
● Discovery of a novel human T-cell lineage expressing T-cell receptor gamma/delta. Collaboration with other groups allowed us to identify T cell receptor gamma/delta by biochemical means. Independent work led to the generation and diagnostic use of the first antibody that could identify cells expressing T cell receptor gamma/delta in human blood and tissues.
● Discovery of the signal transduction complex associated with human membrane immunoglobulin, alias the B cell antigen receptor (BCR, a term coined by our group).
● Implication of various signaling molecules in the BCR pathway, including Btk, c-Cbl and its mechanism of action.
● Identification of TNF receptor family member CD27 and its ligand CD70 as an important T cell costimulatory system, critical for the generation of effector and memory T cells.
● Elucidation of the mechanism underlying ceramide production in response to apoptotic stimuli.
● Discovery of a novel mechanism of ubiquitination that regulates apoptosis signaling by death receptors.
- Evert de VriesTechnician - labmanager
- Yanling Xiao MD. Ph.D.Senior Research Scientist
- Inge VerbruggeResearch associate
- Victoria Iglesias Guimarais, Dr.Postdoctoral fellow
- Tomasz AhrendsPh.D. Student
- Bert van de KooijPh.D. Student
- Nikolina BabalaPh.D. Student
- Paula KroonTechnician
- Joanna GrabowskaMaster Student
- Renske Muns-de JongOffice Manager
Evert de Vries
Technician - labmanager
Thirty years ago I started as a technician on the division of Immunology at the NKI and joined Jannie Borst on her PhD research project (T3/T cell receptor complex). In 1987 I got a permanent position. Also the work relation with my boss turned out to be a permanent one. In 1992 our group joined the division of Biochemistry. In 2002 we returned to Immunology again. Also since 2002 I am, besides a technician, also lab manager on this department. Furthermore I help out as a teacher in the radioactivity 5B course. In the past 30 years I have worked on several, mainly biochemical, projects in a very nice stimulating and inspiring scientific environment!
Current research interest: Apoptosis and Ubiquitination.
Yanling Xiao MD. Ph.D.
Senior Research Scientist
I graduated from Tongji Medical University in 1986, and worked as ENT doctor for 5 years in China. I received my PhD degree from Japan Oita Medical University in 1997. Since 1999, most years I have been working at the NKI, as postdoctoral fellow and later on as senior post-doctoral fellow. I have long-standing experience with all technical approaches in projects investigating the role of TNF receptor family members in T and B immunity. Over the past 5 years, I have conceived, carried out and supervised new research on translating our mouse results to the human situation, in hematopoiesis & osteoimmunology and act as (co-)project leader.
My research is focused on improving the therapeutic effect of localized radiotherapy using highly specific compounds (antibodies) that stimulate cells of the immune system, a treatment called 'radio-immunotherapy'.During my post-doc time at the Peter MacCallum Cancer Centre inMelbourne,Australia, we have shown that radio-immunotherapy could cure mice bearing established mammary (breast) tumours. At the moment, I am continuing this work at the NKI in two main projects: (1) Investigating the potential of radio-immunotherapy in highly relevant mouse models of melanoma and (2) Investigating the cellular and molecular mechanism that underlie the response to radio-immunotherapy.
Victoria Iglesias Guimarais, Dr.
I did my PhD at the Autonomous University of Barcelona where I studied the molecular mechanisms behind the final steps of apoptosis. During my training I was fascinated by the environment of a dying cell, specifically its interaction with immune cells.
Optimizing the therapeutic effect of cancer therapies by engaging the immune system is a novel approach to combat cancer. To purposely make cell death immunogenic, it is essential to study the interactions between the dying cell and immune cells.
In October 2013 I joined Prof. Borst's group to study at the molecular and cellular level what makes radiotherapy immunogenic in a triple-negative breast cancer mouse model. This work is carried out in collaboration with Dr. Inge Verbrugge.
I studied biotechnology at the Intercollegiate Faculty of Biotechnology, University of Gdańsk, Poland. Following an internship at UCSF I started working on my PhD project at the NKI. In our lab we are studying the key molecular mechanisms that optimize cytotoxic CD8 T cell responses as a result of CD4 T cell help. We make use of an experimental model in which we administer DNA vaccines to mice and engage CD4 T-cell help or not. In this way, we can identify the contribution of CD4 T cell help, at which stage it needs to be delivered and what is the molecular mechanism underlying this help. Our findings are important for vaccination strategies against cancer and infectious disease.
Bert van de Kooij
Cancer cells encounter many stress stimuli during oncogenesis and tumor growth that would normally induce apoptosis, a form of programmed cell death. However, cancer cells evolved strategies to evade apoptosis. We want to elucidate these strategies. We focus on how protein level, and subcellular localization of essential apoptosis regulatory molecules is determined, paying special attention to ubiquitination, a posttranslational modification. Unraveling the biology of the ubiquitination of these substrates will increase our understanding of apoptosis, how cancer cells block this, and how we can remove the blockade to kill cancer cells.
I received a MSc degree in biology from Jagiellonian University (Kraków, Poland) in 2006, and in medical biotechnology from Wageningen University in 2011. In April 2010 I joined the group of Prof. Jannie Borst to work on the role of co-stimulatory molecules in shaping the adaptive immune response.
I have completed my BSc in Biochemistry in 2008. After this, I have done a PhD at the University of York (UK) working on prostate cancer (stem) cells. Since October 2013, I have start working as a technician with Dr. Inge Verbrugge in the group of Prof. Jannie Borst.
Currently, I am working on a project which is focused on improving the therapeutic effect of localized radiotherapy using highly specific compounds (antibodies) that stimulate cells of the immune system, a treatment called 'radio-immunotherapy', in which we use highly relevant mouse models of melanoma.
I originate from Poland and am a 2nd year MSc Biomedical Sciences student at the UvA. My first master internship was carried out at the AMC in a stem cell research group (Prof. J.P. Medema) where I studied the cell death response of colon cancer spheroid cultures to betulinic acid (BetA). Currently, I am doing my second internship in the Division of Immunology at the NKI (group Prof. J.Borst) under supervision of Dr.Y. Xiao. For the next 8 months, I will test candidate cell surface markers for their utility to define human common myeloid precursors and downstream macrophage-dendritic cell-osteoclast precursors.
Renske Muns-de Jong
I support the researchers from the division Immunology with administrative and organizing tasks.
I arrange appointments and meetings and coordinate the ordering of materials and central organization of computer facilities.
I assist group leaders within our division, among other things, with publications, grant proposals and annual reports.
Key publications View All Publications
CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production
J Clin Invest. 2010; 120: 168-78.
Peperzak V, Xiao Y, Veraar EA, Borst J.Link to pubmed
CD27 instructs CD4+ T cells to provide help for the memory CD8+ T cell response after protein immunization
J Immunol. 2008; 181: 1071-1082.
Xiao Y*, Peperzak V*, Keller AM, Borst J. * equal first authorLink to pubmed
Recent publications View All Publications
The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17 cells and attenuates associated autoimmunity
Immunity 2013; 38: 53-65.
Coquet JM, Middendorp S, van der Horst G, Kind J, Veraar EA, Xiao Y, Jacobs H, Borst J.Link to pubmed
Ubiquitination by the membrane-associated RING-CH-8 (MARCH-8) ligase controls steady-state cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor 1
J Biol Chem. 2013; 288: 6617-28.
van de Kooij B, Verbrugge I, de Vries E, Gijsen M, Montserrat V, Maas C, Neefjes J, Borst J.Link to pubmed
Renske Muns-de Jong
+31 20 512 2055
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