Summary project

Atopic dermatitis (AD) is a chronic inflammatory disorder characterized by skin lesions, itch, pain, sleep disturbances, and multiple comorbidities with significant decrease in quality of life. It affects up to 20% of children and 10% of adults, and effective and safe treatment options for moderate-to-severe AD have long been lacking. This has changed by the recent introduction of the first biological, the IL-4R blocking antibody dupilumab, blocking both IL-4 AND IL-13 signalling. Dupilumab is effective in reducing AD, but also induces an unexpected side-effect: up to  30% of the patients develop a moderate to severe conjunctivitis needing anti-inflammatory treatment. The mechanism of drug-induced conjunctivitis development is unclear, which severely hampers clinical management. Furthermore, an alternative biological for AD treatment is expected to enter the market this year: tralokinumab, an IL-13 blocking developed by Leo Pharma. In phase III trials tralokinumab was shown to be effective, but there were also signs of conjunctivitis. Therefore the development of reliable tools to understand, classify, and test treatment of AD ocular comorbidities (disease- or drug-related) are urgently warranted.

In this project we aim to

  1. Determine conjunctival goblet cell numbers, cellular infiltrate, and tear fluid immune environment in AD patients, before, and after the start of dupilumab, or tralokinumab treatment.
  2. Perform single cell-sequencing on conjunctiva epithelium of healthy individuals, and AD patients before and after the start of dupilumab or tralokinumab treatment to unravel developmental changes and affected pathways.
  3. Develop 2D and 3D differentiated conjunctiva epithelial organoid model systems using patient-derived cells to test the effect of specific cytokines and treatments on conjunctiva epithelial cell functions, and goblet cell diffentiation in specific.

By developing these novel molecular tools and technologies to understand and diagnose ocular comorbidities, we will be able to (1) identify patients at risk, (2) determine the effect of (novel) therapeutics, (3) develop a precision medicine approach for AD but also other patient groups with ocular co-morbidities.

As a postdoc you will be in the lead of the project. You will be responsible for setting up the assays, performing the experiments, analysing the data and writing down/presenting the findings. You will be part of a multidisciplinary team and will closely collaborate with a physician scientist who will include patients and relevant materials for analysis. The project will give you the chance to interact with many disciplines and to learn novel technologies and analyses such as single-cell sequencing and setting up organoid cultures. 

Afdeling

As a postdoc you will be embedded within the center for translational immunology (van Wijk group), which provides an excellent immunology research infrastructure. This project is a collaboration between the center for translational immunology, the dermatology (Prof Marjolein de Bruin) and ophthalmology departments and the cellular disease model group (Prof Jeffrey Beekman) at the UMC Utrecht. Our multidiciplinary team consists of basic, translational, clinical and computational scientists with successful research lines in mechanisms of chronic inflammatory disease, immune regulation, biomarkers & precision medicine and working mechanisms of biologics.  

Profiel

If you like the combination of clinically relevant research and diving into the mechanisms by setting up new techniques, then this might be a position for you. We are looking for a motivated postdoc with an immunology/cell biology background. Because of the multidisciplinary nature of the project you have to be a teamplayer that is willing to look beyond a specific discipline. Experience with the mentioned techniques is a pre. 

Sollicitatieprocedure

Neem contact op

Wilt u meer informatie over deze vacature? Neem dan contact met ons op.

Femke van Wijk

+31 88 75 542 75 Stuur een email