Dietmar Zaiss

Background

2017 - current    Reader in Immunology, University of Edinburgh / Institute of Immunology and Infection Research

2013 - 2017    Lecturer in Immunology and Chancellor's Fellow, University of Edinburgh / Institute of Immunology and Infection Research

2006 - 2013    Group Leader, University of Utrecht, The Netherlands, Faculty of Veterinary Medicine (Immunology)

2002 - 2005    Post-Doc, University of Rochester, NY, USA- Dr. Tim Mosmann (Immunology)

1996 - 2000    Ph.D., Humboldt University, Berlin - Dr. P-M. Kloetzel (Cell Biology)

1993 - 1996    M.Sc. Syracuse University, NY, USA - Dr. John Belote (Cell and Molecular Biology)

Undergraduate teaching

Course Organizer “Clinical Immunology & Haematology” CI&H-3 (co-chaired together with Julia Dorin) for Third-Year / “Junior Honours” students. This course runs during the Spring semester 

Participates in the courses

-           “Molecules, Infection and Immunity” (MII-2) for Second-Year students, which runs during the Spring semester.

-           “Immunology - 3” for Third-Year students, course runs during the Autumn semester. 

-           “Molecular Immunology” and “Immunobiology” for Forth-Year / “Immunology Honours” students, courses run during the Autumn semester.

-           Master Course "Vaccines and Molecular Therapies", during the Spring semester

In addition, organises a weekly, department-internal “Immunology Refresher Training” for post-graduate students & supervises lab-based, scientific 10 weeks “Honours Projects” 

Research summary

https://orcid.org/0000-0003-3596-7062

The overarching aim of our research is to understand how local immune responses are orchestrated to maintain tissue homeostasis under inflammatory conditions. Specifically, we want to understand the crosstalk of tissue resident immune cells and the surrounding tissue and to understand the underlying molecular mechanisms by which pro- and anti-inflammatory stimuli determine the outcome of local immune responses. Deficiencies in local immune regulation often lead to inflammation-associated diseases, such as fibrotic diseases, atherosclerosis or arthritis, as well as to auto-immune diseases or allergies. Thus, a better understanding of the fundamental mechanisms that regulate local immune responses are of central importance in order to find more efficient ways of treating such diseases.

Our research has revealed that the immune system has adapted the evolutionary conserved signalling pathway of the Epidermal Growth Factor Receptor (EGFR).

For instance, we found that the EGF-like growth factor Amphiregulin is a cytokine expressed by leukocytes, contributing to resistance to helminth infection. (Zaiss et al. Science 2006). Recently, we then revealed that Amphiregulin is achieving this by enabling the formation of hetero-complexes / signalling clusters between the EGFR and IL-33R on the surface of Th2 cells. These hetero-complex/clusters enable Th2-cells to express IL-13 upon exposure to IL-33. In this way, at the site of infection, Th2-cells contribute to worm expulsion in an antigen-independent way. (Minutti et al. Immunity 2017).

Furthermore, we discovered that a crosstalk between the EGFR and TGFβ controls local immune responses. Based on a “biased agonism” of the EGFR, the low-affinity EGFR ligand Amphiregulin induces the local activation of TGFβ (Minutti et al., Immunity 2019). In this way, Amphiregulin enhances the suppressive capacity of regulatory T-cells, thereby critically contributing to the resolution of inflammation and tissue homeostasis. (Zaiss et al. Immunity 2013). TGFβ is expressed and stored in tissues in form of a latent complex. As a low-affinity EGFR ligand, Amphiregulin induces a tonic sustained signal which activates integrin-αV complexes on target cells and thus induces the local release of bio-active TGFβ. In this way, Amphiregulin contributes to local immune suppression and the differentiation of tissue residential stem cells, such as pericytes, and thus to tissue repair. (Minutti et al.  Immunity 2019).

This rather unexpected concept of local immune regulation challenges and suggests the re-evaluation of several of our present perceptions with regard to inflammation, wound repair and tissue homeostasis; and, thus, also their implications for the development of tissue fibrosis, cancer and auto-immune diseases.

We are further exploring the fundamental implications of this novel avenue of research and apply our findings for the development of a sophisticated therapeutic research programme in order to translate this knowledge to the benefit of patients.

 

View all 28 publications on Research Explorer