Max Delbrück Center and German Cancer Consortium support appointment
Prof. Johannes Huppa © Charité | Sebastian Drum
Joint press release from the Charité and the Max Delbrück Center
On September 1, Prof. Johannes Huppa took over the professorship for tumor immunology at the Charité – Universitätsmedizin Berlin and, with it, the management of the Institute for Immunology at the Berlin Buch campus. He will conduct research at the Max Delbrück Center and in the German Consortium for Translational Cancer Research (DKTK). The proven expert in T cell recognition wants to clarify the mechanisms of immunological differentiation between self and foreign in detail in order to improve the treatment of cancer and autoimmune diseases.
What is foreign to the body and what is part of the body? The central sensor of the immune system that makes this distinction is the so-called T cell receptor. Johannes Huppa, who worked at various US institutions and most recently at the Medical University of Vienna before moving to the Charité, has been studying the molecule and how it works for over 25 years. He has significantly expanded our understanding of the molecular processes surrounding the receptor, particularly with the help of innovative microscopy techniques. Johannes Huppa is now succeeding Prof. Thomas Blankenstein, who headed the Charité’s Institute of Immunology until the end of 2020. His working group will be located in the premises of the Max Delbrück Center in Berlin Buch, where he will have a connection as a translational guest group. His work is also funded by the DKTK.
T cell receptors sit like feelers on T cells, which, as part of the acquired immune response, constantly patrol the blood, tissue and organs like a clearing squad. If the feelers perceive fragments presented to them by other cells as foreign, they trigger immune reactions – the intruders are eliminated. If the T cell receptors recognize the fragments presented as part of the body’s own, they remain silent. “The distinction between self and foreign occurs with astonishing precision and is also extremely sensitive,” explains Johannes Huppa. “A patrolling cell can use its T cell receptors to detect a single foreign fragment on the surface of an infected body cell, hidden among a thousand fairly similar but self-producing fragments.”
On the trail of self-other recognition with new “magnifying glasses”
How important this recognition mechanism is for health becomes clear when it does not work perfectly or is faulty: If the distinction between friend and foe does not work, the body may inadvertently turn its immune system against itself, for example – an autoimmune disease such as multiple sclerosis or type 1 diabetes develops. Or the immune system may not recognize degenerated tumor cells, which can then become a deadly threat. Increased infections may also occur.
Johannes Huppa wants to find out exactly how a T cell receptor binds to different fragments and which signals it transmits within the T cell, which then decide between self and foreign. To do this, he has developed new microscopy techniques that allow him to watch living T cells at work. The technique makes individual receptor molecules on the cell surface, the fragments presented and the molecular bonds between them visible. This makes it possible to measure the tiniest mechanical forces in real time and to observe the activation processes within the T cell. In Berlin, he will combine these techniques with synthetic biology methods and structural biology approaches in order to clarify the molecular processes of fragment recognition in time and space with the highest resolution, i.e. on a millisecond and nanometer scale.
Influencing T cell receptors to treat cancer and autoimmune diseases
The immunologist’s goal is to find ways to intervene in the function of the T cell receptor. This should make cancer therapies more effective. “If we understand exactly how the T cell receptor achieves its immunological feat, we can better exploit the potential of new immunotherapies such as CAR-T and TCR-T cell therapy,” explains the new institute director. He also wants to use the knowledge to advance the development of new vaccines against cancer and to eliminate harmful T cells in autoimmune diseases or rejection reactions after an organ transplant.
“To achieve this, collaboration with clinical colleagues at the Charité is essential,” emphasizes Johannes Huppa. “The immediate proximity to the experts in structural biology and tumor immunology at the Max Delbrück Center and the excellent technological infrastructure on the Berlin Buch campus will also be crucial to achieving these goals. The Berlin location is known beyond Germany’s borders for its strength, versatility and active collegiality in basic and clinical research. I am very pleased to now be part of this great network.”
Italics
Johannes Huppa (*12 May 1967 in Thuine, Emslandkeis) studied biochemistry at the Free University of Berlin and researched T cell receptors in his diploma thesis at the Massachusetts Institute of Technology (MIT) in Cambridge, USA. He continued these studies as part of his doctoral thesis at MIT and Harvard Medical School, and in 1998 he received his doctorate from the Vrije Universiteit Amsterdam. First as a postdoctoral fellow and then as a Basic Science Research Associate, he conducted research at the Stanford University School of Medicine in the San Francisco Bay Area before being appointed assistant professor at the Medical University of Vienna in 2012. From 2015 he headed the immune recognition working group at the Center for Pathophysiology, Infectiology and Immunology as an associate professor.
Contact
Prof. Johannes Huppa
Director of the Institute of Immunology
Charité – University Medicine Berlin
T: +49 30 450 570 400
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