Herold Lab

Focus of Research 

The research at Herold Lab 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 defining pathways and mediators of organ regeneration in the context of viral infection. We focus on the interaction of macrophages with parenchymal cells of the distal lung and the epithelial stem cell niche.

Moreover, we study mechanisms that lead to increased susceptibility to bacterial infections during viral pneumonia or acid aspiration with a focus on alveolar macrophages. These aims will be achieved by using established models of in vivo virus infection, acid aspiration and bacterial superinfection of different levels of complexity (in vitro – ex vivo – in vivo) combined with analyses of patient samples.

In an attempt to define better tools for the modelling of human lung diseases we have established a complex human lung organoid system (BTO) derived from human induced pluripotent stem cells (iPSC). Over time, these organoids mimic the branching morphogenesis of native human fetal lungs and can be used to study genetic mechanisms that affect lung development as well as for infection experiments.

We utilize state-of-the-art technologies such as FACS and cell sorting (LSR Fortezza, FACSAriaIII) as well as spectral cell sorting with our recently acquired FACSDiscover S8 cell sorter with CellView Imaging, NGS including single cell RNA-Seq, organoid modeling, and high-resolution microscopy/life imaging techniques. The ultimate goal is to find novel disease biomarkers defining susceptibility to and recovery from ALI, and to identify distinct host targets to be harnessed for novel therapeutic strategies to combat severe respiratory viral infection, and bacterial superinfections due to viral or non-infectious insults in the lung.

Susanne Herold
Prof. Dr. med. Susanne Herold, PhD

Lab Members

PostDocs

Irina Kuznetsova

Irina Kuznetsova, PhD

Project description: In severe cases SARS-CoV2 disease-2019 (COVID-19), virus-induced pneumonia leads to development of disseminated intravascular coagulation, endothelial leakage, acute respiratory distress syndrome (ARDS) and multi-organ failure. The main goal of my project is to elucidate the molecular cross-talk between alveolar epithelial cells, tissue-resident alveolar macrophages and pulmonary microvascular endothelial cells in order to develop an approach for treatment of SARS-CoV2-induced lung injury.

Learta Pervizaj

Dr. biol. Hom. Learta Pervizaj-Oruqaj

Project description: This project is dedicated to elucidate the intricate mechanisms governing lung damage and recovery during severe Influenza A virus (IAV) infections, with a primary focus on alveolar macrophages and their expression of Placenta-expressed transcript 1 (Plet1). The project’s objectives encompass the advancement of our comprehension of the macrophage-epithelial cell crosstalk, ultimately preserving lung function and mitigating severe viral pneumonia consequences. Additionally, we are committed to delve into Plet1’s mode of action and signal transduction pathways it engages, to provide profound insights into lung repair, paving the way for innovative approaches to address respiratory infections and improve patient outcomes.

Margarida Barroso

Margarida Barroso, PhD

Project description: Mesenchymal stem cells (MSC) show promising therapeutic potential in different forms of acute lung injury. However, it is not clear how MSC sense injury during viral lung infections. The aim of this project is to understand how the anti-viral and tissue-protective effects of bone marrow derived-MSC (BM-MSC) are mediated and can be applied in the context of influenza-virus (IV) infection.

Christina Malaino

Christina Malainou, PhD

Project description: Influenza virus-induced pneumonia initiates a variety of immune responses within the alveoli, which eventually compromise host defense, causing the depletion of the local, tissue-resident alveolar macrophage (TR-AM) pool, which paves the way for the establishment of secondary bacterial infections, with a potentially lethal outcome. In this project, we aim to elucidate the pathomechanisms behind influenza-associated TR-AM loss to attenuate disease progress and prevent the transition to post-influenza bacterial pneumonia.

Maximiliano Ferrero

Maximiliano Ferrero, PhD (Guest Scientist)

Project description: The immune response to severe respiratory infections can contribute to lung damage, but it is also crucial to promote repair once the infection is resolved. By unraveling the immune-epithelial cell cross talk, we study how alveolar macrophages mediate epithelial regeneration to preserve the lung during severe viral pneumonia.

PhD Students

Theresa Schäfer

Theresa Schäfer

Project description: The granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to have a beneficial effect on epithelial repair in acute lung injury. We investigate how GM-CSF facilitates alveolar epithelial repair in severe influenza virus pneumonia and examine the underlying GM-CSF-mediated molecular mechanisms.

Afaq Mushtaq

Afaq Mushtaq

Project description: Stem cells niches in the lung are known for promoting tissue regeneration and helping in the resolution of infection. However, the implication of aged stem cell niches is not yet fully understood in the context of influenza-infections. The aim of this project is to establish in vitro models to determine how the age-related reprogramming of the lung stem cell population affects the outcome of infection and how to modulate therapies to improve cellular function.

MD students

Maximilian Löwe

Maximilian Löwe

Dorgeline Blanche Nganko

Dorgeline Blanche Nganko

Technical staff

Larissa Hamann

Larissa Hamann

Florian Lück

Florian Lück

Julia Stark

Julia Stark

Josefine Guth

Laboratory Veterinarian

Sandra Rinnert

Sandra Rinnert

Study Nurses

Nicole Tewes

Nicole Tewes

Magda Zanella

Alumni

Dr. med. Martin Langelage

Jun-Prof. Dr. Ana Ivonne Vazquez-Armendariz

Christin Peteranderl, PhD

Dr. rer. Nat. Lucie Sauerhering

Jennifer Quantius, PhD

Dr. Carole Schmoldt

Dr. Julia Bespalowa

Balachandar Selvakumar, PhD

Lina Jankauskaite, MD PhD

Anna-Lena Ament, M.Sc.

Featured Publications

  • Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia

    2. Januar 2024

    Nat Commun. Pervizaj-Oruqaj L, Selvakumar B, Ferrero MR, Heiner M, Malainou C, Glaser RD, Wilhelm J, Bartkuhn M, Weiss A, Alexopoulos I, Witte B, Gattenlöhner S, Vadász I, Morty RE, Seeger W, Schermuly RT, Vazquez-Armendariz AI, Herold S. Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral […]

  • Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting

    2. Oktober 2023

    J Clin Invest. Malainou C, Abdin SM, Lachmann N, Matt U, Herold S. Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting. 2023 Oct 2;133(19):e170501. doi: 10.1172/JCI170501.

    Alveolar macrophages (AMs) are the sentinel cells of the alveolar space, maintaining homeostasis, fending off pathogens, and controlling […]

  • Cyclosporin A Reveals Potent Antiviral Effects in Preclinical Models of SARS-CoV-2 Infection

    15. April 2022

    Am J Respir Crit Care Med. Sauerhering L, Kuznetsova I, Kupke A, Meier L, Halwe S, Rohde C, Schmidt J, Morty RE, Danov O, Braun A, Vadász I, Becker S, Herold S. Cyclosporin A Reveals Potent Antiviral Effects in Preclinical Models of SARS-CoV-2 Infection. 2022 Apr 15;205(8):964-968. doi: 10.1164/rccm.202108-1830LE. […]

  • Multilineage murine stem cells generate complex organoids to model distal lung development and disease

    2. November 2020

    EMBO J. Vazquez-Armendariz AI, Heiner M, El Agha E, Salwig I, Hoek A, Hessler MC, Shalashova I, Shrestha A, Carraro G, Mengel JP, Günther A, Morty RE, Vadász I, Schwemmle M, Kummer W, Hain T, Goesmann A, Bellusci S, Seeger W, Braun T, Herold S. Multilineage murine stem cells […]
  • Toward a universal flu vaccine

    21. Februar 2020

    Science. Herold S, Sander LE. Toward a universal flu vaccine. 2020 Feb 21;367(6480):852-853. doi: 10.1126/science.aba2754.

Funding & Cooperation Partners

Herold Lab is always open for collaborations with partners from academia, industry, and the public sector. We are interested in translating our research findings into practice and jointly developing innovative solutions. Funding is a crucial part of our work, enabling us to conduct our research at the highest level. Therefore, we appreciate any contribution that supports us in achieving our goals. Please feel free to contact us for more information.