Postdoc position on advancing precision medicine in Systemic Sclerosis developing 3D skin models to uncover drug-response signatures 80 - 100%

Systemic sclerosis (SSc) is a chronic autoimmune fibrotic disease characterized by multiorgan involvement, in-cluding skin and lung. SSc is highly heterogeneous, and its disease trajectory is difficult to predict. Despite recent improvements in survival, SSc remains the rheumatic disease with the highest morbidity and mortality.
The pharmacological management of SSc varies based on clinical manifestations and disease progression. Cur-rent treatment options include mycophenolate mofetil, methotrexate, nintedanib, rituximab, and tocilizumab. However, these therapies primarily manage symptoms rather than modifying the disease course, underlying the need for more targeted interventions.
With the rise of -omics technologies, it is now possible to perform deep phenotyping of patient-derived material, facilitating the identification of novel therapeutic targets. A key challenge is accounting for how baseline medica-tions influence gene expression and cell phenotypes. Correcting for these effects could facilitate the identification of novel targets, paving the way for more effective disease-modifying treatments.
Additionally, modelling drug-response gene signatures could help identify patients who are most likely to benefit from specific therapies, enabling a more personalized and targeted approach to treatment.
In the first stage of the project, you will focus on establishing a SSc skin model using precision-cut tissue slices (PCTS). The PCTS model is derived from skin explants, preserving the native 3D cellular structure, extracellular matrix, and microvascular architecture, which are crucial for accurately recapitulating the pathophysiology of SSc. In parallel, you will develop 3D skin equivalents, incorporating various cell types derived from both SSc pa-tients and healthy donors. These engineered skin constructs will enable the study of cellular crosstalk, fibrotic pathways, and immune interactions in a controlled environment, providing a complementary platform to the PCTS model.
In the second stage, both PCTS and 3D skin equivalents will be treated with drugs commonly used in SSc man-agement, such as mycophenolate mofetil, methotrexate, nintedanib, rituximab, and tocilizumab. These treat-ments will allow for the evaluation of drug responses. For the analysis, you will employ a combination of classical molecular biology assays and cutting-edge single-cell technologies.
Single-cell RNA sequencing (scRNA-seq) to profile transcriptomic changes at a cellular resolution, providing in-sights into cell-specific drug responses and disease mechanisms. By integrating functional assays with high-dimensional single-cell analyses, this project aims to uncover drug-response signatures, improve patient stratifi-cation, and ultimately guide personalized therapeutic strategies for SSc.