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This project investigates how tertiary lymphoid structures shape immune responses across disease contexts, from inborn errors of immunity (APDS) to lung cancer and lung transplantation, with the aim of identifying new therapeutic targets.
We offer a 4-year PhD position investigating how tertiary lymphoid structures (TLS) shape local immune responses in different disease contexts and how they can be targeted therapeutically.
Tertiary lymphoid structures (TLS) are organized immune structures that can arise in tissues during chronic inflammation and disease. Although TLS are increasingly recognized as important sites of local immune activation, their formation, function and therapeutic potential remain poorly understood across different disease contexts. Understanding how TLS are structured and influence local immune responses may reveal new opportunities for therapeutic intervention.
You will study TLS across several disease settings. As part of the IMBRAIN project, you will collaborate with researchers at Erasmus MC investigating TLS in the meninges of murine models of activated PI3Kδ syndrome (APDS), an inborn error of immunity associated with immune and neurodevelopmental abnormalities. In parallel, you will lead the investigation of TLS and local immune responses in tonsillar samples from APDS patients, creating a bridge between experimental models and human immunology.
You will also investigate TLS in lung cancer and lung transplantation, comparing their organization and immune composition within the same tissue but across different disease environments. By integrating these disease contexts, you will identify common and disease-specific mechanisms that shape TLS and determine which features could serve as therapeutic targets. With these findings you will guide the development of targeted nanomedicine approaches, including modified lipid nanoparticles designed to modulate local immune responses.
To address these questions, you will use a broad range of state-of-the-art techniques, including flow cytometry, advanced imaging, molecular and transcriptomic analyses, laser-capture microdissection, and the generation and characterization of lipid nanoparticles. You will work in an interdisciplinary environment combining expertise in immunology, tissue biology, neuroscience and clinical research, with opportunities for collaboration across UMC Utrecht, Erasmus MC and the Wilhelmina Children’s Hospital.
You will be based in the laboratory of Dr. van den Broek within the Center for Translational Immunology (CTI) at UMC Utrecht. The group focuses on understanding T and B cell interactions in health and disease and how these evolve over time. The group is actively involved in collaborative research and has a growing research environment, including an established PhD researcher. You will also work closely with the Van Wijk group in tissue immunology, providing a broader team of researchers and PhD students, regular scientific exchange, and a supportive PhD community.
You will also be part of the IMBRAIN project group at Erasmus MC, led by Dr. V. Dalm and Dr. I. da Silva Serra. The Erasmus MC group will focus on murine models, while the UMC Utrecht group will investigate human immunology, creating a bridge between experimental models and human disease. You will participate in joint group projects and meetings.
The CTI is a well-equipped department with broad expertise in immunology and is part of the Infection and Immunology focus area at UMC Utrecht. Its structure facilitates close integration of fundamental research with clinical translation. Through the CTI and collaborations with UMC Utrecht and Utrecht University, you will have access to advanced technologies including spectral flow cytometry, confocal imaging, mass spectrometry, and scRNA sequencing.
We seek a skilled and driven PhD candidate with a background in biomedical sciences. You should possess outstanding experimental abilities and ideally have some experience in cell culture, (spectral) flow cytometry, RNA sequencing, and analysis of large datasets. Affinity with immunology is desirable, along with a curiosity to investigate various lymphoid structures. Effective communication and organizational skills are essential. The ideal candidate will demonstrate flexibility, adaptability, and a strong ability for teamwork.
Het UMC Utrecht wil bijdragen aan een gezond leven en een gezonde maatschappij, ook voor de generaties na ons. Daarvoor is veel kennis nodig. Als academisch ziekenhuis doen we wetenschappelijk onderzoek naar verschillende ziekten en de werking van onze genen.
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