Staal lab – Molecular Stem Cell biology and lymphoid development
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Our lab is one of the few worldwide successfully translating fundamental research into clinical applications, particularly in the area of gene therapy. We are conducting clinical trials, notably having initiated the world's first trial for RAG1 SCID gene therapy. Collaboration with patient advocacy groups, such as IPOPI and the Dutch SAS, is integral to our research efforts. We also emphasize public engagement through media appearances, lectures, patient information materials, and postgraduate education for medical professionals.
…Our lab is one of the few worldwide successfully translating fundamental research into clinical applications, particularly in the area of gene therapy. We are conducting clinical trials, notably having initiated the world's first trial for RAG1 SCID gene therapy. Collaboration with patient advocacy groups, such as IPOPI and the Dutch SAS, is integral to our research efforts. We also emphasize public engagement through media appearances, lectures, patient information materials, and postgraduate education for medical professionals.
Gene Therapy of Immunodeficiencies
Our research focuses on optimizing and clinically translating gene therapy for immunodeficiencies, particularly RAG1 and RAG2 deficiencies. With over 15 years of preclinical work, we are advancing lentiviral gene therapy using codon-optimized RAG1 in hematopoietic stem cells. In an ongoing clinical trial, five patients have demonstrated excellent immune reconstitution. Our preclinical pipeline also includes lentiviral gene therapy vectors for BTK and RAG2 deficiencies. To further improve accessibility, we have established the CURE4LIFE consortium, which aims to enhance the availability of gene therapy for patients (https://www.lumc.nl/projecten/cure4life/).
T cell development
T cell development is closely linked to hematopoietic stem cell (HSC) differentiation. Unlike other hematopoietic lineages, T cells develop in the thymus, where they are seeded by T cell progenitors from the bone marrow. Our research investigates the dynamics of hematopoietic clones that populate the thymus and differentiate into mature T cells. We also use xenotransplant models to study human immunodeficiencies, examining developmental arrest due to specific mutations. Techniques such as single-cell RNA sequencing, functional assays, and in vivo transplantation into NSG mice are employed to explore human T cell development. Additionally, we investigate how disruptions in Wnt signaling contribute to T cell developmental arrest and lymphoid leukemia.
Molecular signals in HSC
The development and function of hematopoietic stem cells (HSCs) are central to our research. Understanding the molecular signals that drive HSC growth and differentiation is essential for improving therapies, such as bone marrow transplants. Our lab investigates the signals that regulate HSC behavior, focusing on Wnt and Notch signaling pathways. By understanding how these signals affect hematopoietic differentiation, we aim to manipulate them to improve transplantation outcomes.