Immune Cell Engineering & Development
Using iPSC to decode and engineer human immune cell development and function.
In the van der Stegen (VDS)-Lab we combine iPSC-based in vitro models and humanized mouse models to study human lymphocyte development and model immune cell interactions within immune organs and tumor microenvironments. The enhanced understanding of the developmental and environmental cues on immune cell function and behavior will inform the design of the next generation, iPSC-derived, cellular therapies.
Research
T cell lineage commitment
T cell lineage commitment is in part driven by TCR rearrangement and selection. In vivo, iPSC-derived T cells can also undergo these processes, and produce mature cells which closely resemble primary cells. However, they still have distinct differences. By using a combination of iPSC-derived in vitro models alongside humanized in vivo models, we aim to enhance our understanding of TCR selection mechanisms and how these can be mimicked in vitro for the generation of allogeneic, therapeutic, applications.
Synthetic immune organs
Immune responses are continuously shaped through cell:cell interactions. We are building synthetic immune organs (such as the thymus and germinal centers) and tumor microenvironments to support the design of engineering strategies to enhance these interactions.
Humanized mouse models
We are developing humanized mouse models which support the establishment of human lymphocyte populations and facilitate in vivo CRISPR-screen technology to study transcriptional control of human lymphocyte development and function.