Scientific Basis
Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting over 60 million people worldwide. Although cytokine-targeted biologic therapies have transformed treatment, an increasing number of individuals do not respond to or fail these drugs, a group referred to as biologic-refractory psoriasis. An emerging option for management of these patients is cell-based therapy, particularly mesenchymal stromal cells (MSCs) which are rapidly gaining attention as a promising and potentially curative approach for inflammatory diseases, including psoriasis.
We recently treated three adults with severe, biologic-refractory psoriasis using MSCs from umbilical cord with striking results. Each patient experienced up to 90% skin improvement, lasting for as long as six months. Interestingly, after MSC treatment, two of the three patients regained responsiveness to previously failed biologic drugs. Clinical improvement in psoriasis seen with MSC treatment was paralleled by an increase in circulating regulatory T cells (Tregs)—which play a key role in reducing inflammation. These findings suggest that MSCs may “reset” the immune system in part through the action of Tregs.
Project Aim
To investigate how Tregs contribute to MSC-induced immune reset and restored responsiveness to biologics, by comparing Tregs from psoriasis patients receiving MSCs or standard-of-care biologics as part of a clinical trial scheduled to start in January 2026.
Techniques & Skills
The student will lead the project and develop highly sought-after skills in advanced multiparameter imaging flow cytometry, spectral-flow cytometry and in vitro immune-monitoring and functional assays. Following appropriate training, they will analyse multi-omics patient data using high-dimensional bioinformatics. Based on results obtained, follow-up experiments may include single-cell RNA sequencing and gene-editing techniques via collaborative partnerships. This blend of wet-lab and computational expertise will provide an excellent springboard for careers in translational immunology, precision medicine, or biotech R&D.
Objectives
• Year 1: To design imaging flow cytometry assays to study FOXP3 transcription factor expression in Tregs. Simultaneously, to design and develop spectral-flow cytometry panels to deeply phenotype Treg subsets. Begin analysing pre- and post-treatment patient samples using both platforms.
• Year 2: To complete cohort sample analysis. To apply high-dimensional analysis to study Treg subsets in MSC-treated vs biologic-treated patients.
• Year 3: To design and perform follow-up functional assays to explore mechanisms of MSC-induced Treg modulation.
• Year 4: Complete data acquisition and integration, write thesis, and prepare publications.
3-Month Rotation Project
The student will use healthy volunteer samples to establish imaging flow cytometry assays to study FOXP3 transcription factor activation in Tregs.