KFO309 - The clinical research unit Virus Induced Lung injury

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VIRUS-INDUCED LUNG INJURY:

PATHOBIOLOGY AND NOVEL THERAPEUTIC STRATEGIES

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Acute lower respiratory tract infections represent an increasing public health problem worldwide, and result in a disease burden greater than that of any other infection, with mortality rates unchanged over the past 50 years. Likewise, the lack of any pharmacological treatments for the most devastating clinical course of pulmonary infection, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), underscores an urgent medical need for novel, eff ective therapeutic approaches. Recent studies revealed that viral infection is the underlying cause of the majority of community-acquired pneumonia (CAP) among children, and in 41% of adult patients with CAP-associated ARDS. Current antiviral treatments are only available for infl uenza virus (IV) infection, but they are of very limited effi cacy and bear the risk of rapid acquisition of viral resistance. Ge- netic susceptibilities together with specifi c pre-conditions or co-morbidities are major risk factors for severe courses of respiratory viral disease, characterized by defi ciencies in adequate antiviral control and/or exaggerated infl ammation and tissue damage. In addition, there is increasing evidence that respiratory virus infection frequently predisposes for severe gram-positive bacterial superinfections with fatal outcome. Emergence of novel respiratory viruses such as pH1N1/2009 pandemic IV and highly pathogenic avian IV strains, or the Middle East Respiratory Syn- drome Coronavirus (MERS-CoV) which causes substantial mortality among children and adults further highlights the need for a better understan- ding of the underlying pathobiology.

Against this background, the Clinical Research Unit (CRU) program is dedicated to unraveling the mechanisms driving anti-viral host defense, to dissecting the cellular and molecular contributors to the tissue damage at the virus-host interface in the distal lung, and to defi ning pathways and mediators of organ regeneration in the context of viral infection. These aims will be achieved by using established virus infection models of diff erent levels of complexity (in vitro – ex vivo – in vivo) combined with analyses of patient samples derived from diff erent lung compartments (e.g. bronchoalveolar lavage fl uid [BALF], lung tissue, isolated lung cells, resident and invaded myeloid cells) and, prospectively, fi rst-in-man diagnostic and therapeutic approaches. The ultimate goal and vision of this initiative is to fi nd novel disease biomarkers defi ning susceptibility to and recovery from lung viral attack, and to identify distinct host targets to be harnessed for novel therapeutic strategies to combat severe respirato- ry viral infection and associated lung injury.

We will address these goals in a concerted and comprehensive 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 (JLU) and its Medical Faculty, as well as into the research focus `microorganisms and infection biology` of the Philipps University Marburg (UMR), formally joined by the universities of Marburg and Giessen research alliance.

KFO309 ist funded by the German Research Foundation DFG from 2017 to 2019.

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