NOMIS Awardee Andrea Ablasser from EPFL, Switzerland, virologist Glen Barber from Ohio State University, US, and biochemist Zhijian “James” Chen from the University of Texas Southwestern Medical Center at Dallas, US, were awarded the 2025 Paul Ehrlich and Ludwig Darmstaedter Prize. The award honors the scientists’ discovery of the cGAS–STING signaling pathway, the alarm system that sounds when, in the event of infection, cancer or cellular stress, DNA enters a cell’s plasma, activating the innate immune system.
Awarded by the Paul-Ehrlich Institut, the Paul Ehrlich and Ludwig Darmstaedter Prize recognises special contributions to the research fields for which Paul Ehrlich was an advocate. These fields include immunology, cancer research, haematology, microbiology, and chemotherapy. The Paul Ehrlich Foundation awards the prize, endowed with €120,000, to one or more researchers annually. The award ceremony takes place each year on Paul Ehrlich’s birthday, the 14th of March, in the Paulskirche in Frankfurt. Traditionally, the Paul-Ehrlich-Institut invites the laureate or laureates to visit the institute. Prizewinners Professor Glen Barber and Professor Zhijian Chen accepted this invitation and presented their research at a scientific colloquium at the Paul-Ehrlich-Institut on the day of the award ceremony.
The discovery of and research on the cGAS–STING signalling pathway has not only expanded our understanding of fundamental immunological processes, but has also provided an important impetus for biomedical research. The prizewinners’ work creates the basis for innovative therapies that modulate the body’s immune defences in a targeted manner – a promising approach for the development of new medicinal products against infections, cancer, and inflammatory diseases,
emphasised Professor Stefan Vieths, President of the Paul-Ehrlich-Institut.
The cGAS–STING Signalling Pathway
If double-stranded DNA (dsDNA) appears in the cell’s interior in the wrong place – such as in the cytoplasm – this triggers the highest alert level for the body. Such DNA comes either from viruses or from damaged cells. Our immune system must respond immediately. How the innate immune defence recognises this danger has long been unclear. The three laureates discovered the mechanism responsible for sounding the alarm between 2008 and 2013 and have been researching it ever since.
Ohio State University virologist Glen Barber provided crucial insights into the discovery of STING. He illustrated the central role this protein plays in the immune defence in his lecture at the Paul-Ehrlich-Institut. If, for example, DNA is present in the cytoplasm of a cell due to a viral infection, the stimulator of interferon genes (STING) becomes active. STING gives the nucleus the signal to produce special messenger substances – interferons. These interferons ensure that the infected cell and the surrounding tissue are put on alert and the immune defence is activated.
How STING learns that dsDNA has appeared in the cell plasma and is recognised by the immune system as a danger was discussed in the second colloquium lecture. Biochemist Zhijian “James” Chen of the University of Texas Southwestern Medical Center in Dallas identified the enzyme cGAS as a central sensor that detects the emergence of DNA in the cytoplasm and decoded its molecular function. The cGAS sensor does not distinguish between foreign and the cell’s own DNA. This makes sense because the cell’s own DNA usually only appears in the nucleus and mitochondria – not in the cytoplasm. If the cell’s DNA enters the cytoplasm, such as when there is cancer present, cGAS sounds the alarm and activates the immune system. This system protects against infections and cancer, but also carries risks: If cGAS is incorrectly activated by the cell’s own DNA, it can lead to autoimmune diseases.
Physician Andrea Ablasser from the École polytechnique fédérale de Lausanne further elucidated the importance of the cGAS–STING signalling pathway for infections, cancer defence, and autoimmune diseases. As we age, the cGAS–STING signalling pathway is apparently activated more frequently – even without an infection. This process, known as a sterile inflammation, can presumably contribute to the development of heart failure, diabetes, and autoimmune diseases. Active ingredients are being researched that specifically inhibit the signalling pathway in order to prevent sterile inflammations. Andrea Ablasser and her team succeeded in synthesising the first STING inhibitor in 2018.
Conversely, studies are also being conducted to investigate whether certain active substances that activate the cGAS–STING pathway can help to fight cancer cells more effectively.
Go to this Paul-Ehrlich Institut release: Scientific Colloquium with the 2025 Paul Ehrlich and Ludwig Darmstaedter Prizewinners: How the Immune System Recognises DNA as a Danger
