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 underlying molecular mechanisms by which pro- and anti-inflammatory stimuli determine the outcome of local immune responses, thus preventing the development of pathology and ultimately disease.

A critical but rather enigmatic modulator of local inflammation is the Transforming Growth Factor β (TGFβ). TGFβ is a pleiotropic cytokine. TGFβ controls the type and magnitude of local immune responses and contributes to tissue repair. Mice with deficiencies in TGFβ signalling develop autoimmunity, while mice that overexpress TGFβ develop tissue fibrosis. The functionality of TGFβ is regulated on several different levels, such as by the local transformation of TGFβ from a latent into its bio-active form, and by the variable sensitivity of target cells to its action. However, how TGFβ function is regulated under various inflammatory conditions remains largely unresolved.

Over the last decade, our research has revealed that the immune system has adapted the evolutionary conserved signalling pathway of the Epidermal Growth Factor Receptor (EGFR) (Zaiss et al., Science 2006). 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 and type-2 cytokine, Amphiregulin, induces the local activation of TGFβ (Minutti et al., Immunity 2019), while the high-affinity EGFR ligand and pro-inflammatory cytokine, HB-EGF, activates the intra-cellular inhibitor of TGFβ signalling, TGIF, and thus blocks TGFβ signalling in target cells, such as CD4 T-cells.

As distinct inflammatory stimuli induce the differential expression of these two antagonistic cytokines and EGFR ligands, the expression pattern of these two cytokines/growth factors reflects the state of inflammation and thus directly links the state of inflammation with the local activity of TGFβ. Thus, a cross-talk between the EGFR and TGFβ is a central regulator of local inflammation.

This rather unexpected concept of local immune regulation challenges and suggests the reevaluation 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 intend to further explore 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 22 publications on Research Explorer