ESR 1: Initiate a pilot prevention trial in individuals at high risk for developing rheumatoid arthritis

Host:

Prof. Dr Ronald van Vollenhoven

Amsterdam Rheumatology and immunology Center (ARC)

Department of Rheumatology & Clinical Immunology

Amsterdam UMC, location AMC

Duration: 48 months

The PhD candidate will plan and initiate a clinical trial in individuals who are at high risk of acquiring rheumatoid arthritis (RA); this work will include developing the protocol, obtaining the necessary approvals, and establishing the needed collaborations. At-risk individuals will be identified using a combination of clinical and laboratory variables, and randomly assigned to treatment with an immunomodulator or placebo. [Full project description].

 

ESR 2: Clinical studies of treating-to-target in patients with systemic lupus erythematosus

Host:

Prof. Dr Ronald van Vollenhoven

Amsterdam Rheumatology and immunology Center (ARC)

Department of Rheumatology & Clinical Immunology

Amsterdam UMC, location AMC

Duration: 48 months

The PhD candidate will plan and initiate a pilot clinical trial for patients with systemic lupus erythematosus (SLE) to test the proposed strategy of “treating-to-target” (T2T) with remission as the target. This work will include developing the protocol, obtaining the necessary approvals, and establishing the needed collaborations. Patients will be randomly assigned to T2T vs. regular care treatment. [Full project description].

 

ESR 3: Gene expression in the HLA complex in autoimmune disease

Host:

Prof. Dr. Niek de Vries

Amsterdam Rheumatology and immunology Center (ARC)

Rheumatology & Clinical Immunology & Experimental Immunology

Amsterdam UMC, location AMC/VUMC

Duration: 48 months

In most autoimmune diseases the most strongly associated genetic variation is located in the human leukocyte antigen region (HLA). HLA gene products have a major role in the induction and regulation of the adaptive immune response. In this project we will use state-of-the-art high-throughput sequencing approaches to study the role of gene expression and gene splice variants in different autoimmune diseases. [Full project description].

 

ESR 4: Clonal isotyping of the B cell response in autoimmunity

Host:

Prof. Dr. Niek de Vries

Amsterdam Rheumatology and immunology Center (ARC)

Rheumatology & Clinical Immunology & Experimental Immunology

Amsterdam UMC, location AMC/VUMC

Duration: 48 months

High-throughput sequencing studies show that clonal B cell responses play a key role in many autoimmune diseases. The autoantibodies produced come in different isotypes and subtypes, each with different functional characteristics. Using novel high-throughput sequencing technology we aim to unravel the isotype history and characteristics of the autoantibody response in different diseases, and its relevance for response to B-cell directed therapies. [Full project description].

 

ESR 5: Study the molecular and cellular features of human lymph node T cells during the earliest phases of systemic autoimmunity

Host:

Dr Lisa van Baarsen

Amsterdam Rheumatology and immunology Center (ARC)

Department of Experimental Immunology

Amsterdam UMC, location AMC

Duration: 48 months

The PhD candidate will focus on determining the frequency, phenotype and function of exhausted/senescent T cells in lymph node biopsies obtained from healthy individuals, RA-risk individuals and RA patients. In addition, the PhD student will delineate the mechanism of the reduced cytokine production observed in autoimmune lymph node T cells and investigate whether this defect can be restored. [Full project description].

 

ESR 6: Mesenchymal stromal cells as key orchestrators in RA

Host:

Dr Lisa van Baarsen

Amsterdam Rheumatology and immunology Center (ARC)

Department of Experimental Immunology

Amsterdam UMC, location AMC

Duration: 48 months

The PhD candidate will perform in depth molecular and cellular analyses of stromal cells derived from bone marrow, lymph node and synovial tissue biopsies obtained during the earliest (preclinical) phases of RA. The ultimate goal is to identify targets that can be manipulated to regulate stromal cell function, which may lay the foundation for preventive intervention and immunomodulation. [Full project description].

 

ESR 7: The B cell lineage in ANCA-associated vasculitis: functional characterisation and identification of novel targets

Host:

Dr. S.W. Tas

Department of Rheumatology & Clinical Immunology

Laboratory for Experimental Immunology

Amsterdam UMC, location AMC/VUMC

Duration: 48 months

The PhD candidate will investigate the B cell lineage in ANCA-associated vasculitis aimed at functional characterisation and identification of novel targets. This research project will be the first to investigate B lineage cells in AAV in 3 different compartments of the immune system: peripheral blood, lymph nodes and bone marrow. We will use a novel cutting edge technology such as multi-parameter CyTOF PhosphoFlow, RNA- and ChIP-sequencing. Ultimately, we will also validate various therapeutic targets in an animal model of AAV. These types of experiments have not been performed previously and the impact of the findings is likely to reach beyond AAV, as it may simultaneously advance our understanding of fundamental B cell biology in general and of principles that are shared between AAV and other systemic autoimmune diseases such as primary Sjögren’s Syndrome, SLE and RA. [Full project description]

 

ESR 8: State-of-the-art in vivo PET-CT imaging of immune cell subsets in chronic inflammatory diseases and cancer

Host:

Dr. S.W. Tas

Department of Rheumatology & Clinical Immunology

Laboratory for Experimental Immunology

Amsterdam UMC, location AMC/VUMC

Duration: 48 months

The PhD candidate will develop PET-CT imaging of immune cell subsets and soluble mediators in chronic inflammatory diseases and cancer. This research project will be truly translational: we will start with in vitro studies to develop novel tracers, followed by in vivo studies in preclinical models and ultimately proof-of-concept studies in humans, including correlation of imaging results with ex vivo tissue analysis. The overarching goal of this project is to develop a novel strategy to visualize to what extent these diseases are driven by specific immune cell subsets or certain soluble mediators in the individual patient, which may ultimately predict to what therapy the individual patient may respond best (i.e. checkpoint inhibitors, cytokine inhibitors or depleting antibodies). This concept will also be tested in disease models. These unique experiments have not been performed previously and the impact of the findings is likely to be big, as it may advance our understanding of pathological processes that play an important role in these diseases and ultimately guide treatment decisions. [Full project description]

 

ESR 9: Characterize the molecular pathways activated during the pre-clinical phase of spondyloarthritis

Host:

Dr Marleen van de Sande

Amsterdam Rheumatology and immunology Center (ARC)

Department of Rheumatology & Clinical Immunology

Amsterdam UMC, location AMC

Duration: 48 months

The PhD candidate will perform in depth cellular and molecular analysis of target tissue (joint, lymph node, gut, skin) collected during the pre-clinical phase in the spondyloarthritis-like HLA-B27 transgenic rat model as well as in biosamples collected from individuals at risk of developing axial spondyloarthritis. The ultimate goal is to identify novel treatment targets to halt or prevent inflammation and new bone formation in axial spondyloarthritis. [Full project description].

 

ESR 10: Pharmacokinetics and immunogenicity of therapeutic antibodies in inflammatory bowel disease and spondyloarthritis: A RESEARCH PROJECT ON THE EDGE BETWEEN GASTROENTERLOGY AND RHEUMATOLOGY

Hosts:

Prof Dr Geert D’Haens

Gastroenterologist| Professor

Dr Marleen van de Sande

Amsterdam Rheumatology and immunology Center (ARC)

Department of Rheumatology & Clinical Immunology

Amsterdam UMC, location AMC

Duration: 48 months

The PhD candidate will perform in depth analysis of molecular profiles related to immunogenicity and treatment responses in inflammatory bowel disease and spondyloarthritis. In this project we aim to improve understanding of how to prevent and treat immunogenicity, as well to improve prediction of response/failure to treatment in inflammatory bowel disease and spondyloarthritis. [Full project description].

 

ESR 11: Understanding auto-immune disorders through computational modelling.

Hosts:

Prof. dr. A.H.C. van Kampen (Antoine)

Bioinformatics Laboratory

Clinical Epidemiology, Biostatistics, and Bioinformatics

Amsterdam UMC, location AMC

https://bioinformatics.amc.nl/

 

Dr Lisa van Baarsen

Amsterdam Rheumatology and immunology Center (ARC)

Department of Experimental Immunology

Amsterdam UMC, location AMC

Duration: 48 months

The molecular and cellular mechanisms underlying autoimmune disorders such as rheumatoid arthritis are not well understood. In this project we aim to combine (single cell) omics data and (multi-scale) computational modelling to gain further insight in these disorders [Full project description].

 

ESR 12: Bioinformatics analysis of T-cell and B-cell repertoires.

Host:

Prof. dr. A.H.C. van Kampen (Antoine)

Bioinformatics Laboratory

Clinical Epidemiology, Biostatistics, and Bioinformatics

Amsterdam UMC, location AMC

https://bioinformatics.amc.nl/ 

Duration: 48 months

Adaptive Immune Receptor Repertoire (AIRR) sequencing is used to determine the T-cell and B-cell repertoires to study adaptive immune responses in health and disease. It has been used to investigate immune responses in autoimmune disorders such as rheumatoid arthritis. In this project we will focus on the development and application of bioinformatics methods for the analyses of (public) AIRR-seq data [Full project description].

 

ESR 13: Unravelling the role of B-cells in ANCA-associated vasculitis

Host:

Paul Klarenbeek, MD, PhD

Rheumatologist

Department of Rheumatology & Clinical Immunology

Laboratory for Experimental Immunology

Amsterdam UMC, location AMC

Duration: 48 months

Vasculitis is an auto-immune inflammation of vessel walls which stops the blood flow and leads to organ failure and sometimes death as a result. There is a pressing need to understand the pathogenesis of vasculitis to improve patient care and outcome. Recently, we showed that the presence of certain B-cells in blood correlates with disease activity in vasculitis and our data suggests that these cells can be used in clinical practice to steer therapy (Al Soudi, 2019 Arthritis Res Ther). In this project we will unravel the mechanism behind this correlation and develop/improve tests to steer our care for patients. To this end, the PhD student will characterize B-cells of interest using state-of-the art techniques such as Next-Generation-Sequencing of B-cell receptor repertoires and Transcriptome Sequencing. The PhD student will have access to unique materials from our outpatient vasculitis expertise center. [Full project description]

 

ESR 14: Activated PI3 kinase delta in systemic lupus erythematosus (SLE)

Hosts:

Prof. dr. Sergey Nejentsev

Department of Molecular Cell Biology and Immunology

Amsterdam UMC, location VUMC

Prof. dr. Alexandre Voskuyl

Department of Rheumatology

Amsterdam UMC, location VUMC

Duration: 48 months

The PhD candidate will search for biomarkers of activated PI3 kinase delta and will study these biomarkers in cohorts of SLE patients. This project will identify a subgroup of SLE patients with chronically activated PI3 kinase delta and will open ways for personalized therapy of such patients using a new class of drug, PI3 kinase delta inhibitors [Full project description].

 

ESR 15: Uncovering how HIV hides in immune cells: metabolic reprogramming of CD4 T cells during infection

Host:

Dr. Jeroen den Dunnen

Amsterdam Rheumatology and immunology Center (ARC)

Rheumatology & Clinical Immunology

Experimental Immunology

Amsterdam UMC, location AMC

Duration: 48 months

HIV is the virus that causes AIDS. One of the main obstacles for an HIV cure is the so-called viral reservoir where HIV ‘hides’ in particular cells of individuals, and where it persists despite decades of therapy. Our recent research has identified a key factor that drives HIV reservoir formation. In this project, the PhD student will delineate how this drives infected cells to become HIV reservoir cells. The project will combine molecular and cellular immunology, virology, and (immuno)metabolism, in order to find new ways to counteract HIV reservoir formation, and to thereby work towards the ultimate goal finding an HIV cure [Full project description].

 

ESR 16: Metabolic reprogramming of human myeloid immune cells during chronic inflammation

Host:

Dr. Jeroen den Dunnen

Amsterdam Rheumatology and immunology Center (ARC)

Rheumatology & Clinical Immunology

Experimental Immunology

Amsterdam UMC, location AMC

Duration: 48 months

Inflammatory disorders such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) are characterized by chronic inflammation of the joints and the intestine, respectively. For both diseases, pro-inflammatory cytokines such as TNF play a key role, but it is still unclear which (combination of) factors drives the excessive TNF production by immune cells. Our findings highlight a key role for C-reactive protein (CRP), which promotes excessive inflammation in both diseases through induction of metabolic reprogramming of immune cells such as macrophages. The main goal of this project is to identify the metabolic and cell signaling pathways that underlie CRP-induced inflammation in RA and IBD, in order to identify new targets for therapy [Full project description].

 

ESR 17: Immune monitoring of macrophages in the development and progression of rheumatoid arthritis and immune checkpoint inhibitor-induced rheumatic manifestations

Host:

Dr Conny J. van de Laken

Department of Rheumatology

Amsterdam UMC, location VUMC

Duration: 48 months

The PhD candidate will be involved in clinically-directed laboratory studies exploring macrophage biomarkers for PET imaging with the aim to monitor early development, progression and treatment response of the disease in patients with classical rheumatoid arthritis (RA) patients and in cancer patients experiencing rheumatic manifestations as an immune-related adverse event following treatment with immune checkpoint inhibitors. Studies will include (macrophage) immune monitoring of RA and cancer patients, and PET imaging of macrophage markers and immune checkpoints in arthritic animal studies. [Full project description].

 

ESR 18: Molecular imaging of angiogenesis and therapeutic effects of anti-angiogenetic agents in rheumatoid arthritis

Host:

Dr Conny J. van de Laken

Department of Rheumatology

Amsterdam UMC, location VUMC

Duration: 48 months

This project is focused on development of detection and therapeutic monitoring of angiogenesis in rheumatoid arthritis (RA) using innovative molecular imaging techniques. In the project novel imaging biomarkers for Positron Emission Tomography (PET) that target angiogenesis will be developed and investigated for their potential to detect angiogenesis in RA and monitor therapeutic effects of anti-angiogenetic agents. [Full project description].

 

ESR 19: Development of immune competent gut on chip model

Hosts:

Prof. Dr. Sue Gibbs/ Prof. Dr. Reina Mebius

Department of Molecular Cell Biology and Immunology

Amsterdam UMC, location VUMC

Duration: 48 months

This project is focused on developing an immune competent organotypic gut on chip for testing immune responses and uptake of orally ingested drugs for RA. This project will combine cutting-edge research in gut, lymphatic drainage, and immunology with advances in tissue engineering, including organ on chip. This project will work in parallel to, and combine in the final year, with the project aimed at developing organotypic lymph node on chip. [Full project description].

 

ESR 20: Development of immune competent lymph node on chip model including lymph node stromal cells, lymphocytes, and dendritic cells.

Hosts:

Prof. Dr. Sue Gibbs/ Prof. Dr. Reina Mebius

Department of Molecular Cell Biology and Immunology

Amsterdam UMC, location VUMC

Duration: 48 months

This project is focused on developing an immune competent lymph node on chip for mimicking human adaptive immune responses and the control of these responses by the lymph node stromal cells. This project will combine cutting-edge research on lymph node stromal cells and adaptive immunity with advances in tissue engineering, including organ on chip. This project will work in parallel to, and combine in the final year, with the project aimed at developing organotypic gut on chip. [Full project description].