all staff members
Dr. rer. nat.
Monika Heiner
scientific lab manager
Project
Macrophages play an important role in the innate host defense against pathogens. In addition to their pro-inflammatory properties, they can also contribute to repair processes. We are particularly interested in the macrophage-epithelial crosstalk in the repairing lung. In this project, we want to identify soluble mediators which promote lung regeneration from a local epithelial progenitor cell pool using a 3D co-culture model and microarray analysis.
Dr. rer. nat.
Barbara Sprenger
scientific administrator
Dr. rer. nat.
Corinna Bremer
scientific administrator KFO 309
Sandra Rinnert
Laboratory Veterinarian
Post Docs
Ivonne Vazquez-Armendariz
Project
The aim of my PhD work is to elucidate the role of GM-CSF (granulocyte-macrophage colony stimulating factor), a well-known differentiation factor for myeloid cells, in alveolar repair after influenza virus infection. Our preliminary data suggest that GM-CSF mediates proliferation and differentiation of distinct epithelial progenitor cell subsets of the distal lung and therefore represents a key player in alveolar epithelial repair after injury.
Christin Peteranderl , PhD
Project
A hallmark in the pathogenesis of influenza A virus-induced ARDS is the accumulation of excessive fluid in the alveolar airspace, which causes severe edema and impairs gas exchange. Clearance of this edema fluid is driven mostly by vectorial transport of sodium ions by the alveolar epithelial Na,K-ATPase, creating an osmotic gradient that passively removes water from the alveoli. As edema clearance is a crucial determinant for survival of patients with ARDS, we study the regulation of the Na,K-ATPase after IV infection, focusing on both direct host-virus interactions as well as paracrine signaling networks within the infected lung.
Dr. biol. hom.
Learta Pervizaj Oruqaj
Dr. rer. nat.
Lucie Sauerhering
Project
Emerging Coronaviruses (CoV) such as the Middle East Respiratory Syndrome (MERS)-CoV are causative agents of acute lung injury, however, drugs providing protection against emerging CoV are lacking. Targeting cyclosporine A-/ immunophilin-related cellular signaling pathways, this project aims to define antiviral and lung-injury attenuating compounds to provide ready-available treatment strategies for ongoing and future emerging CoV. With Lucie Sauerhering employed as Postdoc with longstanding BSL4 working-experience, the project will run as a close cooperation project between the Herold lab with its expertise in the molecular pathogenesis of acute lung injury and the lab of Stephan Becker located in Marburg providing renowned expertise in the field of molecular virology of highly pathogenic viruses.
Dr. med.
Ulrich Matt
,
PhD
Project
Acute lung injury (ALI) is caused by direct or indirect insults to the lung, and is associated with high morbidity and mortality. Bacterial superinfections are feared complications of ALI. On the cellular level, alveolar macrophages are key innate immune cells that initiate and resolve an inflammatory process. Resolution of inflammation might impair the macrophage´s ability to clear bacteria, thus predisposing to superinfections. My project focuses on the kinetics and activation state of macrophages/monocytes during ALI in the context of bacterial superinfections.
Balachandar Selvakumar , PhD
Project
The main goal of my project is to investigate the role of macrophages and its functional phenotypes in host defense and in regeneration processes of the lung epithelium in vivo and in vitro and to characterize their gene expression profiles by single cell RNASeq during pneumonia-induced ARDS using mouse models of ALI/ARDS. In addition, the project is also designed to identify crucial effector molecules in distinct macrophage functional phenotypes, broadly termed M1 and M2, which could be targeted therapeutically for the treatment of IAV induced lung injury to attenuate epithelial injury and drive stem cell-mediated lung repair.
Julia Spengler , PhD
PhD students
Christina Malainou , MD
Project
`Strategies to prevent influenza-induced loss of the alveolar macrophage pool and improve host defense against secondary infection`
Bacterial superinfection after influenza virus (IV)-induced lung injury significantly contributes to disease severity and mortality. The pathogenesisis characterized by mutual interactions between the co-infecting pathogens and the host. One important mechanism is the depletion of a specific subset of lung macrophages called resident alveolar macrophages (rAM), which act as first line innate immune defense by phagocytosing invading bacteria in the alveolar space. rAM death in vivomay be driven by both the viral infection itself and host-derived inflammatory signals. Currently, the respective contribution of these processes and the downstream signaling pathways involved are largely unresolved. Aim of this project is to characterize infection-induced death pathways in rAM, develop strategies to inhibit them and restore rAM function as well as assess the effect of rAM protection/restoration on a bacterial superinfection level.
Bacterial superinfection after influenza virus (IV)-induced lung injury significantly contributes to disease severity and mortality. The pathogenesisis characterized by mutual interactions between the co-infecting pathogens and the host. One important mechanism is the depletion of a specific subset of lung macrophages called resident alveolar macrophages (rAM), which act as first line innate immune defense by phagocytosing invading bacteria in the alveolar space. rAM death in vivomay be driven by both the viral infection itself and host-derived inflammatory signals. Currently, the respective contribution of these processes and the downstream signaling pathways involved are largely unresolved. Aim of this project is to characterize infection-induced death pathways in rAM, develop strategies to inhibit them and restore rAM function as well as assess the effect of rAM protection/restoration on a bacterial superinfection level.
Margarida Barroso , M.Sc.
Project
The aim of my PhD work is to do an analysis of the molecular interactions between virus-infected lung cells and MSCs (mesenchymal stem cells). Using established murine and human primary alveolar epithelial cells/MSCs co-culture and mouse models of IV-induced lung injury it is aimed that this project identifies transcriptional changes induced in MSC in the context of IV-induced ALI and further characterize the functionality of key signaling molecules mediating the beneficial proven effects of MSC.
Ludmilla Sperling
MD students
Dorgeline Blanche Nganko
Project
The immunomodulatory drug CsA (cyclosporin A) been reported directly inhibit IAV replication in epithelial cells (Liu et al, 2012; Hamamoto et al, 2013). Additionally, our own preliminary work shows that CsA decreases pro-inflammatory mediator expression in infected macrophages that are important drivers of IAV-induced lung injury (Herold et al., 2008; Högner et al., 2013; Peteranderl et al., 2016). However, the detailed signaling mechanisms have not been elucidated to date. Therefore, this project will address IAV replication in primary alveolar epithelial cells and TRAIL expression in primary alveolar macrophages after addition of distinct inhibitors targeting distinct CsA-downstream signaling pathways.
Julia Bespalowa
Project
The host cellular protein kinase R (PKR) binds viral dsRNA and thus plays a central role in IAV detection and the subsequent activation of antiviral signaling cascades. These processes are antagonized by the viral non-structural (NS)1 protein that is able to block PKR activation. Our own preliminary work shows that distinct mutations in the NS1 protein modulate its ability to abrogate PKR activation and type I IFN and other cytokine production in vitro. As both aspects, viral replication and pro-inflammatory cytokine production, contribute to disease progression to ARDS, we will address how distinct NS1-host protein-interaction sites influence IAV-induced lung injury in vivo.
Non-scientific staff
Larissa Hamann
technician
Stefanie Jarmer
technician
Corinna Plate
technician
Nicole Tewes
study nurse
Yascha Seyed Vossoughi
student assistant
Alumni
Jennifer Quantius , PhD
Project
Influenza virus infection is associated with apoptosis of epithelial cells, disruption of the alveolar epithelial barrier and edema formation, which severely affects gas exchange. Structural and functional re-establishment of the injured distal epithelium is therefore crucial for recovery after severe influenza virus-induced pneumonia. Within the distal lung compartment, epithelial stem/progenitor cells strongly contribute to regeneration. Therefore, the underlying molecular mechanisms which foster distal lung stem/progenitor cell-mediated repair of the epithelium are investigated and thereby the interactions between influenza virus and host cell-mediated regenerative pathways are elucidated in order to attenuate lung injury and improve disease outcome.
Dr.
Carole Schmoldt
Project
Alveolar epithelial cells constitute a primary target of influenza virus and are reveal high levels of apoptosis following infection resulting in breakdown of pulmonary barrier function, however, the underlying signaling events remain poorly defined. I am therefore investigating the key host mechanisms involved in lung epithelial cell injury as well as viral pathogenicity factors involved, in order to discover new therapeutic targets for treatment of influenza virus-induced ARDS. Experiments are conducted in vitro (primary human and murine epithelial cells cultures) and in vivo (mouse model), and will systematically elucidate these mechanisms at single cell level using high-purity FACS sorting combined with NGS techniques.
Lina Jankauskaite , MD
Project
Bone marrow-derived mesenchymal stem/stromal cells (MSC) have promising therapeutic potential in different forms of acute lung injury (ALI), and are now in first clinical studies. However, the molecular mechanisms underlying their injury- or pathogen-related beneficial effects within defined niches of the affected lung are poorly understood. In particular, the molecular interactions and pathways of injury sensing by MSC in viral infection of the lung are widely unknown. It is also not well defined, how MSC are recruited to sites of infection or inflammation, and whether distinct subsets of MSC hold different therapeutic potential. Therefore, a detailed analysis of the molecular interactions between virus-infected lung cells and MSC, mediating injury-specific priming and lung homing of defined MSC subsets with particular anti-viral, immunomodulatory and organ repair capacity, is envisioned in this project.