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.Associate staff scientist
- Inge VerbruggeAssociate staff scientist
- Yi-Yen ChenPostdoctoral Fellow
- Victoria Iglesias Guimarais, Dr.Postdoctoral fellow
- Sander de Kivit, Ph.D.Postdoctoral Fellow
- Jara Palomero Gorrindo, Dr.Postdoctoral fellow
- Tomasz AhrendsPh.D. Student
- Nikolina BabalaPh.D. Student
- Astrid BovensTechnician
- Joanna GrabowskaTechnician
- Paula KroonTechnician
- Joost LakemanStudent technician
- 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.
Associate staff 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.
Associate staff scientist
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.
I obtained my PhD in the lab of Prof. Nüsslein-Volhard at the Max-Planck Institute for Developmental Biology in Tübingen, where I worked on how asymmetry of the body plan develops in zebrafish embryos. Recently I have gained a strong interests in cancer immunology, therefore I decided to change my research field and joined Prof. Borst's group. My project is to elucidate by which molecular mechanisms at the transcriptional and epigenetic level CD4 T cells alter the functional capacity of cytotoxic T lymphocytes, in particular with regard to their memory function. Knowing how the helper signals impact on the CTL will greatly advance immunotherapy of infectious diseases and cancer.
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.
Sander de Kivit, Ph.D.
After obtaining my Master in Drug Innovation at Utrecht University, I obtained my PhD at Utrecht University as well. In my studies, I focused on the regulation of dendritic cells and T cell responses in the intestine. I continued these studies as a postdoctoral fellow at Rush University Medical Center in Chicago.
As a postdoc in the group of prof. Borst, I will explore the differences in signaling and metabolism between conventional and regulatory T cells as a target for therapeutic interventions in autoimmunity and anti-tumor responses. This project is funded by a grant from the Institute for Chemical Immunology.
Jara Palomero Gorrindo, Dr.
The immune system and its therapeutic applicability have always intrigued me. Thus, I pursued a MSc in Immunology and a PhD project on the B-lymphocyte malignancy mantle cell lymphoma (MCL). My PhD work has newly identified the neuronal transcription factor SOX11 as an oncogenic driver in MCL and elucidated that SOX11 deregulates B-cell differentiation and promotes tumor angiogenesis via specific target molecules.
Now, I am a postdoctoral fellow at Prof. Jannie Borst's laboratory, where I will be working on a project aiming to identify markers and novel regulators of macrophage, osteoclast and dendritic cell commitment from their common precursors.
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.
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 studied Biology and Medical Laboratory Research in Utrecht from 2005 till 2009 and completed the Neuroscience master in 2011 at the Free University in Amsterdam. I have joined the group of Prof. Jannie Borst in March 2015. Currently, I am working on a project that is collaborative with the company BioNovion. The purpose of this project is to validate an agonistic antibody to human CD27 in a mouse model. We will examine the capacity of this antibody to stimulate the T cell response and in which settings it can optimally be used for immunotherapy of cancer.
I obtained my bachelor in Applied Biomedical Sciences at Robert Gordon University (Scotland) in 2011. After carrying out my honors project at an excellent research institute in Portugal (IPATIMUP), I decided to continue in the cancer research field. Thus, in 2014 I completed an MSc in Biomedical Sciences (track Oncology) at the University of Amsterdam.
Currently, I am working on the project that aims at finding new surface markers to define human myeloid precursors and their downstream dendritic cell, macrophage and osteoclast precursors. In regards to that I am looking at the functional capacity of generated precursor-derived dendritic cells, macrophages and osteoclasts to verify their quality.
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 study Life Science & Chemistry at Inholland
Amsterdam. I focus on the interaction of dendritic cells with CD4+
T cells. When this interaction occurs, the cells form an
immunological synapse which is thought to assist the directional
delivery of signals for CD4+ T-cell activation. In this process,
the T cell
receptor recognizes specific peptides bound to major histocompatibility complex class II on the cell surface of the DC's. We hypothesize that the coordinated delivery of MHC class II compartments to the immunological synapse is a key process in order to induce an efficient priming of CD4+ T cells.
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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