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KFO 309:  Virus-induced Lung Injury: Pathobiology and Novel Therapeutic Strategies

Subject Area Medicine
Term from 2016 to 2024
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Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 284237345
 
Acute lower respiratory tract infections represent an increasing public health problem worldwide, with mortality rates unchanged over the past 50 years, and viral infection is an underlying cause in the majority of community-acquired pneumonias. The lack of any causal therapy for its most devastating course, the acute respiratory distress syndrome, underscores an urgent medical need for novel therapeutic approaches. Current antiviral treatments are only available for influenza infection, but are of limited efficacy and bear the risk of rapid resistance acquisition. Furthermore, the emergence of novel respiratory viruses such as pandemic or highly pathogenic avian influenza, or MERS-Coronavirus further highlights the need for a better understanding of the underlying pathobiology. The Clinical Research Unit (CRU) will unravel the mechanisms driving anti-viral host defense, dissect the cellular and molecular contributors to the tissue damage at the virus-host interface, and define pathways and mediators of organ regeneration in this context. These aims will be achieved by using established virus infection models of different complexity levels (in vitro¿ex vivo¿in vivo) combined with analyses of patient samples derived from different lung compartments and, prospectively, first-in-man diagnostic and therapeutic approaches. The ultimate goal and vision of this initiative is to find novel disease biomarkers defining susceptibility to and recovery from lung viral attack, and to identify host targets to be harnessed for novel therapeutic strategies to combat severe respiratory viral infection and associated lung injury. We will address these goals in a concerted effort within a unique consortium of investigators, comprising basic science and clinical disciplines to cover all aspects important to the fulfillment of our mission. 90% of the projects include investigators with an MD background, and 80% are run by at least one clinician in charge of treating infectious diseases and pulmonary/critical care patients, supported by an established lung biobank. A central project on lung cell genomics will not only serve as a technology platform, but will also systematically integrate the data gained from the various projects and therefore serve as both a central nucleus and a systems medicine backbone of the CRU. It is envisioned to implement this CRU as a permanent translational and clinical unit at the Department of Medicine II, establishing a unique structure to foster and accelerate bench-to-bedside research translation towards patient care, and to improve training of physician-scientists in this particular field of medicine. The CRU thereby perfectly integrates into the research foci `heart & lung disease` and `infection & immunity` of the Justus-Liebig-University, as well as into the research focus `microorganisms and infection biology` of the Philipps University Marburg, formally joined by the universities of Marburg and Giessen research alliance.
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