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

PhD research

Host:

Dr Marleen van de Sande

Rheumatologist| Assistant professor| PhD

Amsterdam University Medical Centers (location AMC)

Meibergdreef 9

105AZ  Amsterdam

The Netherlands

Duration: 48 months

Background

Axial spondylitis (axSpA) is the second most prevalent type of chronic inflammatory arthritis. In the pathogenesis of axSpA innate immune triggering at a site distant of the joint (e.g. gut, skin) results in clinical manifest disease with axial inflammation and new bone formation. With the current available treatments only about 20% of the axial spondyloarthritis patients achieve remission, and new bone formation cannot be prevented. This results in irreversible structural damage of the spine with functional impairment. Possibly the current treatments do not target the right pathologic processes, or treatment is started too late. Our recent findings evaluating treatment effect of anti-IL23R in the HLA-B27 transgenic rat model of spondyloarthritis suggest that IL-23 plays a role in pathogenesis before onset of clinical manifest disease, but not thereafter. We propose that in the pre-clinical phase, before axSpA becomes clinically manifest, specific immune pathways are activated that subsequently trigger chronic inflammation and irreversible structural damage. We have the opportunity  to molecular characterize the pre-clinical phase in great detail in   biosamples collected in an unique inception cohort of first-degree relatives of HLA-B27 positive axSpA patients at risk of development of disease as well as in the SpA-like HLA-B27 transgenic rat model. This innovative approach allows for in depth analysis of pathways related to inflammation and new bone formation in key target tissues in the preclinical phase of disease and to translate findings from experimental models to the clinic.

Approach 

Key objectives are : 1. Identifying molecular pathways activated during the pre-clinical phase in our heat-inactivated Mycobacterium tuberculosis accelerated HLA-B27 transgenic ratmodel.  2. Investigating whether the identified pathways are also present when other immune triggers more relevant to human spondyloarthritis are applied. 3.  Confirm identified pathways in individuals at risk of developing spondyloarthritis.

Our research team

It is our ambition to elucidate the pathways that initiate chronic inflammation and new bone formation from the earliest phases of spondyloarthritis onwards. Findings from our studies will lead to the identification of potential novel treatment targets aiming for remission or even prevention of structural damage to improve outcome and quality of life for spondyloarthritis patients. We work within the Amsterdam Rheumatology and immunology Center (ARC), are embedded in the Amsterdam Infection & Immunity Institute, and  have access to high quality core research facilities of the AMC including e.g. the Animal house, Bio-informatics Laboratory.  This provides an excellent multidisciplinary research environment which form a basis for fruitful scientific collaborations between clinicians and basic scientists on our translational research projects.  The van de Sande group currently consists of 1 PhD student, 2 research nurses, and 1 supportive personnel. This project will be performed in close collaboration with ARCAID PI’s dr. Lisa van Baarsen (transciptomics) and prof. dr. Antoine van Kampen (bioinformatics), as well with our postdocs experienced in animal models. 

Your profile

  • We are looking for a highly motivated and enthusiastic researcher with:

    • - A master degree in Biomedical Sciences, with affinity for translational research and animal studies, and an interest in immunology and/or rheumatology.
    • - Experience with molecular biology, and preferably with animal studies and/or bioinformatics.
    • - You are well organized, and like to show your drive and focus as a researcher.
    • - You enjoy collaborating with both clinicians and basic scientists, and are able to work independently as well as in a team.
    - You have excellent communications skills in English, both written and verbal.

Our offer

All ARCAID ESRs receive a full employment contract for 4 years, according to the Collective Employment Agreement (CAO) of the Dutch University Medical Centres. The monthly salary based on a 36-hour work starts from €2.422,- with yearly increments to a maximum of € 3.103,-. This 4-year PhD position is funded by the  Marie Skłodowska-Curie actions of the European Union's Horizon 2020 COFUND program under grant agreement No 847551. There is no separate budget available for mobility as it is already included in the ESR salary. ESRs may attend external courses, conferences or workshops. If applicable or required, additional expenses for training and conference participation and the travel to a Partner Organisation will be covered by the project. The ESR salary meets the requirements of the Dutch Immigration Department to allow family members to move to the Netherlands. It is at the convenience of the ESR to decide on this family movement since the Amsterdam UMC will not cover additional expenses regarding mobility of spouse nor for the required accompanying residence permits. In addition to their individual scientific projects, all fellows will have the opportunity to attend international progress meetings, scientific conferences and summer schools. Additionally, they benefit from further continuing education, which includes internships and secondments, a variety of training modules as well as transferable skills courses. See recruitment procedure.

Your application

See recruitment procedure. You can apply using the online application form. For more information about the project you can contact Dr Marleen van de Sande.