MA (Oxon), MD, FMedSci, FRCPCH, FMH Paediatrics (CH)
Hoffmann and Action Medical Research Professor of Developmental Medicine
- Head of Department
Understanding the development and function of the immune system in health and disease
Prof. Georg A Holländer was trained in both Paediatrics and Experimental Immunology in Switzerland and the U.S. He held academic positions at Harvard Medical School, Boston, U.S. and the University of Basel, Switzerland, before he joined the University of Oxford, UK (2010). He is interested in the development and function of the immune system in health and disease. His particular scientific focus concerns the molecular and cellular control of thymus development and function.
Funding Panels (present):
Charities in Switzerland - Cancer and Life Sciences focus
Funding Panels (past):
Ongoing D.Phil projects:
The molecular and cellular biology of thymus development and function
The thymic microenvironment is unique in its ability to promote the development of naïve T cells with a repertoire purged of vital “Self” specificities and poised to react to injurious “Non-Self”. Thymic epithelial cells (TECs) constitute the major component of the thymic stroma (in addition to tissue specific fibroblast subpopulations) and can be categorized into separate cortical (c) and medullary (m) lineages based on their specific molecular, structural and functional characteristics. cTEC induce the commitment of blood-borne precursor cells to a T cell fate, foster the subsequent maturation and control the positive selection of antigen receptor bearing thymocytes. In contrast, mTEC promote the terminal differentiation of thymocytes which includes the establishment of immunological tolerance to self-antigens via a deletional mechanism and the generation of natural regulatory T cells. In this way, mTEC generate the self-tolerant T cell repertoire in a direct instructive fashion. This essential capacity depends on the mTEC’s promiscuous expression of a large programme of transcripts that encode proteins which are normally only detected in differentiated organs residing in the periphery (a.k.a. tissue restricted self antigens).
The molecular regulation of TEC development and function remains incompletely understood and thus constitute the research focus of the Developmental Immunology Group Laboratory. Specifically, research is undertaken to better understand the role of individual transcription actors, including the master regulator FOXN1 and its co-factors but also that of epigenetic modifications for TEC differentiation and function. For this purpose, we use state-of-the-art molecular and cellular tools to gain an integrated understanding of the role of the thymus in health and disease.
Developmental dynamics of the neural crest-mesenchymal axis in creating the thymic microenvironment.
Handel AE. et al, (2022), Sci Adv, 8
P63 targeted deletion under the FOXN1 promoter disrupts pre-and post-natal thymus development, function and maintenance as well as induces severe hair loss.
Stefanski HE. et al, (2022), PLoS One, 17
FOXN1 forms higher-order nuclear condensates displaced by mutations causing immunodeficiency.
Rota IA. et al, (2021), Sci Adv, 7
RBFOX splicing factors contribute to a broad but selective recapitulation of peripheral tissue splicing patterns in the thymus.
Jansen K. et al, (2021), Genome Res, 31, 2022 - 2034
Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα).
Bainter W. et al, (2021), Sci Immunol, 6