Our airways are covered by a thin mucus layer that plays a pivotal role in maintaining lung health and homeostasis. In healthy, this mucus layer entraps constantly inhaled pathogens, pollutants and irritants that are then removed from the lungs by beating cilia on airway surfaces that facilitate mucocillary clearance, which constitutes an important innate defense mechanism of the lung. In chronic muco-obstructive lung diseases such as cystic fibrosis (CF) and bronchiectasis the viscoelastic properties of airway mucus are characteristically altered. Increased viscosity and elasticity of the mucus in these diseases leads to impaired mucociliary clearance, which in turn leads to airway mucus plugging, chronic infection with Pseudomonas aeruginosa and other bacterial pathogens, and chronic neutrophilic inflammation. Neutrophils express a group of proteases called neutrophil serine proteases (NSP), including neutrophil elastase (NE), protease 3 (PR3) and cathepsin G (CG). It is well established that increased activity of these NSPs leads to the degradation of endogenous anti-proteases, which in turn causes a protease/anti-protease imbalance that plays a central role in the pathogenesis of progressive structural lung damage in CF and bronchiectasis. Preliminary data from our group suggest that these proteases may also change the viscoelastic properties and function of the mucus by cleavage of the mucins (MUC5B and MUC5AC) that form the mucus layer. However, a systemic evaluation of the effects of NSPs on mucus properties has not been performed and whether proteolytic degradation of mucus is beneficial or detrimental in muco-obstructive lung diseases remains unknown. Finding answers to these questions is also relevant in the context of current development of novel therapies for CF and bronchiectasis that inhibits NSP activity and may thereby also have an effect on mucus properties and mucociliary clearance.
This project aligns with Re-Thinking Health by investigating homeostatic immune control of a common virus, the John Cunningham virus (JCV), by deciphering the identity and function of rare populations of protective T-cells in preventing JCV reactivation and progressive multifocal leukoencephalopathy (PML). Up to 80-90% of all adults are infected with JCV, but the infection rarely causes disease. In contrast, individuals with compromised T cell immunity are at risk of PML, with high mortality and limited treatment options. Resolving antigenic targets and functional identity of protective T-cell responses, will enable design of novel vaccines and enable a more precise risk prediction in at-risk populations, such as patients under immune suppressive therapies. The program’s focus on health as an active regulated biological state, together with its emphasis on prevention-oriented translational research, provides an ideal framework to investigate adaptive immune mechanisms underlying latent viral control and maintenance of organismal health.
Scientific interest centers on the molecular mechanisms that preserve health and resilience with focus on microbiome-host crosstalk, especially microbiome-derived hydrogen sulfide, protein persulfidation, and systemic energy metabolism in organ function. This aligns with the goals of Re-Thinking Health, which aims to define health-preserving pathways and translate them into prevention-oriented strategies.
Rheumatoid Arthritis (RA) represent a chronic and prevalent autoimmune disease characterized by inflammation and progredient joint destruction. Both anti-citrullinated protein antibodies (ACPA) and autoreactive ACPA-producing B cells play a key role in disease pathogenesis. However, the exact mechanisms leading to disease onset remain poorly understood. Notably, ACPA are not only present in RA patients, but can be also detected in a certain fraction of healthy individuals where they are indicating an increased risk of developing RA in the future. The proposed study thus aims to investigate the role of autoreactive ACPA-producing B cells in ACPA-positive healthy individuals and to understand the molecular mechanisms that eventually lead to the onset of inflammatory disease. By focusing on autoreactive B cells, we aim to uncover novel molecular insights into the pathogenesis of RA and identify potential therapeutic targets to prevent disease progression.
The epithelium of the gastrointestinal tract is a single cell layer organized into villi and crypts, which separates microbiota and host. Stem cells in the crypts constantly generate epithelial progenitors that differentiate and migrate toward the villus tip, where they are shed into the lumen. While some of these processes are epithelial-intrinsic, coordinated interactions with underlying stromal cells are essential for tissue morphogenesis, stem cell maintenance, epithelial differentiation and spatial zonation along the crypt–villus axis. Importantly, disruption of this communication not only impairs local tissue integrity but also drives systemic inflammation, metabolic dysfunction, and cancer risk. Understanding these interactions will provide key insights into the mechanisms linking tissue-specific processes to overall organismal health and disease.
The Neumann lab is specifically interested in the molecular basis of immune cell adaption to the GI tract. The goal of our research is to understand the molecular mechanisms that determine the gut-specific functions of distinct immune cell populations. Furthermore, we aim to identify the specific (micro)environmental cues that trigger adaptation of immune cells in the gut. In addition, a major focus of our research lies on the crosstalk between gut immune cells and distinct intestinal tissue cells, such as epithelial or neuronal cell populations, to better understand the cellular networks that are in place to establish and maintain intestinal health.
The goal of my laboratory is to understand the regulation and control mechanisms of immune responses at barrier surfaces specifically in the respiratory tract. We are continuously exposed to the environment by filtering liters of air each minute to provide needed oxygen in exchange to carbon dioxide to our body. A unique network of pulmonary immune cell populations ensures appropriate immune responses not only against pathogens or hazardous materials but to maintain lung function and health at steady state. However, the underlying mechanisms are poorly understood. Group 2 innate lymphoid cells (ILC2s) are the major innate lymphoid immune cell population in the lungs, tissue resident and able to orchestrate innate but also adaptive immune responses. Thus, studying the regulatory processes of ILC2 effector funct
Are you passionate about scientific questions related to understanding the basis of health and disease? Are you interested in applying your findings to answer clinically relevant questions for molecular prevention and the development of novel therapies?
An update on further recruitment rounds will follow shortly.
Apply here.
Our lab investigates fundamental mechanisms of communication between the nervous and immune systems, two major sensory networks that continuously monitor tissue integrity and initiate protective responses upon disruption. While the immune system’s role in maintaining barrier function is increasingly understood, the contribution of neuronal signals to immune regulation remains largely unexplored. Recent work from the lab has revealed how neuropeptides such as neuromedin U and neurotransmitters like norepinephrine modulate innate lymphoid cells (ILCs), key tissue-resident immune cells at mucosal barriers. By integrating advanced genetic tools with state-of-the-art methods from immunology, neuroscience, and genomics, the lab aims to dissect the cellular and molecular circuits of neuro-immune interaction.
Pulmonary hypertension is a common cardiopulmonary disease that is characterized by extensive remodeling of the pulmonary vascular tree and a poor prognosis due to ultimate right heart failure. The underlying progressive lung vascular remodeling involves two distinct but interconnected pathologies: distal capillary loss (vascular rarefaction) and proliferative remodeling of precapillary resistance vessels. Current therapeutic approaches rely on vasodilatory drugs and do not address the underlying causes of vascular remodeling which are poorly understood. Yet, deeper insight into the underlying pathophysiological processes – which forms the basis for the development of causal rather than symptomatic therapies – is hampered by limited access to human biosamples, the restriction to post-mortem end-point analyses in animal models, and the complexity of the multicellular processes driving vascular remodeling which cannot be recapitulated in traditional cell culture. To overcome this gap in methodologies, knowledge and ultimately therapy, we have engaged in a collaboration with a Suisse bioengineering lab to develop in-vitro microvasculature-on-chip and artery-on-chip models that allow for the first time to track changes of the vascular system and the dynamics of individual cell types in an unprecedented temporally and spatially resolved context.1 These models – in combination with advanced imaging modalities, state-of-the-art metabolic assays and functional read-outs – are now ready to use and open up unprecedented avenues for the discovery of new mechanisms of health and disease and the development of new therapeutic targets.
Our group aims to understand the molecular mechanisms involved in tissue homeostasis, inflammation, and resolution of inflammation. Our main focus is on the transcription factor NF-κB and its role in the intestinal epithelium. Our current projects range from determining the role of the transcription factor in epithelial regeneration in colitis and in inflammatory bowel diseases (Re-Thinking Health, 2022), to refining analgesia (Charité 3R), to investigating the role of NF-κB in cellular senescence in the gut (DFG) or its role in metabolism.
Our research aims to understand the role of tissue-resident cells of the innate immune system in the prevention of chronic inflammatory diseases such as systemic lupus erythematosus and inflammatory bowel disease. Our goal is to identify mechanisms that may inhibit the transition from homeostasis to chronic inflammatory disease and to determine the role of tissue-resident cells of the innate immune system in this process. Understanding such mechanisms may allow to answer the question of why some patients are susceptible to chronic autoimmune-related inflammatory diseases and others are not, and how to improve/achieve resistance to chronic inflammatory diseases.
In our project, we focus on maladaptive immune responses to prevent multi-morbidity in patients with chronic kidney disease (CKD). Based on our longstanding interest in microbiome-immune interactions in cardiovascular and renal diseases, the planned project involves first proof-of-concept clinical studies side by side with experimental in vitro assays. Our translational project addresses a molecular mechanism that is crucial to maintain health and opens up areas for preventative strategies in line with the Re-thinking health program.
The gastrointestinal epithelium is organized into clonal crypts that represent sophisticated anatomical and functional tissue units. The epithelium is intimately associated with the mesenchymal stroma network, and various mesenchymal cell types are essential constituents of the stem cell niche that regulates epithelial homeostasis. The gastrointestinal stem cells give rise to differentiated cells. This process is important to maintain the nutritive absorptive functions of the epithelium as well as to build a barrier against pathogens and toxins from the environment. Recently, it has become increasingly evident that interactions between the epithelium and stroma are vital in regulating the barrier function, allowing tissue adaptations to environmental perturbations1,2. Our research aims at understanding the interplay between the epithelium, stroma and the microbiota. We would like to understand how tissues respond to microbiota alterations or exposure to pathogenic bacteria as well as their toxins. To address this, we are also developing new organoid and assembloid models to recapitulate the cellular networks observed in vivo.
Diabetics have a higher risk of various infectious diseases including pneumonia. Current estimates suggest that 450 million people worldwide have diabetes, and this number will increase to approximately 700 million by 2045. The increase in diabetes prevalence is thus likely to cause an increase in pneumonia-related morbidity and mortality. A better understanding of the mechanisms underlying diabetes-related dysregulation of the antibacterial immune response may allow to develop more targeted prophylactic strategies to prevent pneumonia in diabetic individuals.
The airway mucosa represents the first line of defense of the respiratory system against pathogens, pollutants, and irritants that are constantly inhaled during tidal breathing. Elimination of these potentially harmful stimuli by mucociliary clearance is an important innate defense mechanism of the lung, which operates through the coordinated function of (i) the motile cilia, (ii) the airway surface liquid layer, and (iii) the mucus layer.
Acute respiratory distress syndrome (ARDS) is a serious complication of infectious or sterile lung inflammation, typically as a consequence of pneumonia or sepsis, with high morbidity and mortality (30%-40%) and presently no pharmacological or mechanistic treatment strategies. This critical knowledge and treatment gap became strikingly evident in the recent COVID-19 pandemic, with ARDS as the main cause of death1,2. ARDS is characterized by a breakdown of the lung vascular barrier and the leak of fluid from the blood into the airspaces, preventing normal lung mechanics and gas exchange. Traditionally, mechanisms of ARDS are studied in animal models, which have, however, translated poorly into the clinical scenario. Here, we will assess mechanisms of lung vascular barrier integrity and regeneration in a novel microphysiological Microvasculature-on-Chip (MOC) model that allows to track vascular morphology and leak as well as the dynamics of individual cell types and their interaction in an unprecedented temporal and spatial context. Here, we will employ this model for the first time to study lung vascular barrier integrity, and to devise strategies for its maintenance in experimental settings mimicking ARDS.