June 24, 2021, 17:15 CEST - via Zoom

Title: Digitalization and change in health care and research

Speaker: Prof. Dr. Isabelle Bekeredjian-Ding, Head of Department Microbiology, Paul Ehrlich Institut, Germany

Isabelle Bekeredjian-Ding is Head of the Microbiology Division at Paul-Ehrlich-Institut (PEI). She received Medical School training at the University of Heidelberg, Padova (Italy) and Mt. Sinai, New York and clinical residency training in Munich and Heidelberg, Germany. She has a clinical specialization in Medical Microbiology, Virology and Epidemiology of Infectious Diseases and a PhD equivalent and habilitation in immunology. In 2017, she was appointed Associate Professor for Medical Microbiology and Immunology at the University of Bonn, Germany. Before joining PEI she was deputy director of the Institute of Medical Microbiology, Immunology and Parasitology in Bonn. Her research is focused on vaccines against nosocomial pathogens and antibiotic resistance. She is Member of the Vaccines Working Party at EMA and of the EMA pandemic task force as well as Chair of the Scientific Committee of the IMI2 JU program of the European Commission.

Abstract: Digitalization has become an important driver of change in health care and medical research. The evolvement of the Innovative Medicines Initiative, probably the worldwide largest public private partnership in drug discovery and health care founded by the European Commission with the European Federation of Pharmaceutical Industries and Associations exemplifies this. The new funding instruments developed by the European Commission will pursue these developments, thus aiming at data- and technology-driven improvements in health care. This raises the question whether our health care system is prepared to embrace the new technologies, implement them and exploit their potential to face the challenges ahead. Undoubtedly, the COVID-19 pandemic has facilitated the acceptance of digital solutions and demonstrated their usefulness. The lessons learnt will be discussed in the context of development and regulatory approval of COVID-19 vaccines.

June 10, 2021 - via Zoom

Title: STAG2 regulates interferon signaling in melanoma via enhancer loop reprogramming

Speaker: Dr. Lei Gu, Max Planck Institute for Heart and Lung Research, Germany

Abstract: The cohesin complex participates in the organization of 3D genome through generating and maintaining DNA loops. Stromal antigen 2 (STAG2), a core subunit of the cohesin complex, is frequently mutated in various cancers. However, the impact of STAG2 inactivationon3D genome organization, especially the long-range enhancer-promoter contacts and subsequent gene expression control in cancer remain poorly understood. Here we show that depletion of STAG2 in melanoma cells leads to expansion of topologically associating domains (TADs) and enhances the formation of H3K27ac-associated DNA loops at sites where binding of STAG2 is switched to its paralog STAG1. We further identify Interferon Regulatory Factor 9 (IRF9) as a major direct target of STAG2 in melanoma cells via integrated RNA-seq, STAG2 ChIP-seq and H3K27ac HiChIP analyses. We demonstrate that loss of STAG2 activates IRF9 through modulating the 3D genome organization, which in turn enhances type I interferon signaling and increases the expression of PD-L1. Our findings not only establish a previously unknown role of the STAG2 to STAG1 switch in 3D genome organization, but also reveal a functional link between STAG2 and interferon signaling in cancer cells, which may enhance the immune evasion potential in STAG2-mutant cancer.