We study development and function of the innate immune system, in particular of innate lymphoid cells (ILC). A current focus is to obtain a molecular understanding of how the innate immune system, by integrating environmental signals (such as those derived from nutrients, microbiota, circadian rhythm) contributes to tissue physiology. Recent studies have revealed ever more intriguing relationships between innate immune system components and basic developmental and biologic processes that are likely to reveal unsuspected pathways by which the immune system might be plumbed to improve health and healthspan. These lines of research have suggested new functions of the immune system for processes such as tissue homeostasis, morphogenesis, metabolism, regeneration and growth. Our research is developing by crossing boundaries of disciplines (immunology, microbiology, developmental biology, stem cell biology, tumor biology, regenerative medicine etc.) and is, by nature, highly interdisciplinary.
Chronic kidney dysfunction is a major global health concern of increasing prevalence, driving a plethora of secondary comorbidities. A mechanistic understanding of the driving factors is essential to develop preventive and therapeutic concepts.
Our research group investigates microbiome-mediated mechanisms of cardiovascular risk (Wilck et al. Nature 2017; Bartolomaeus et al. Circulation 2019; Avery et al. Cardiovasc Res. 2023). CKD is an understudied risk factor for cardiovascular disease. In the long term, microbiome-targeting interventions could help to reduce cardiovascular risk in CKD patients.
Active maintenance of tissue health requires maintenance of tissue-resident macrophages that perform homeostatic functions. Loss of tissue-resident macrophages reduces the ability of tissues to maintain homeostasis or to return to homeostasis after inflammation. We propose that exploring the mechanisms that maintain tissue-resident macrophages will allow us to identify molecular targets that promote tissue health and to achieve deeper remission after treatment of chronic inflammatory diseases.
Our lab investigates the gastrointestinal (GI) tract epithelium – the cellular layer lining the stomach and intestine that forms a vital barrier between the body and the external environment. A central focus lies on understanding the mechanisms of epithelial regeneration and how interactions with commensal microbiota and pathogenic bacteria influence this process, potentially leading to inflammation, gut dysfunction, or cancer.
Healthy aging is increasingly recognized as a dynamically regulated state requiring active molecular maintenance in a concert of organ systems, among which the immune system takes a conducting role. The Else Kröner-Promotionskolleg “Re-Thinking Health” highlights the importance of studying resilience mechanisms that allow the body to adapt to environmental stressors to maintain (immune) homeostasis. Recent work from the PI lab (Alsaleh et al. 2020; 2025; Zhang et al. 2019; Puleston et al. 2014) and the Co-PI (Hofer et al. 2024) has revealed that the polyamine metabolism, traditionally viewed in the context of cellular proliferation, plays a key role in autophagy regulation and immune cell function. Importantly, we have shown that polyamine metabolism is a critical weak point in maintaining autophagy in advanced age (Hofer et al. 2022). Our recent discoveries have demonstrated that feeding-fasting rhythms in humans increase systemic and cellular polyamine levels and that this is crucial for regulating autophagy (Hofer et al. 2024). A central feature of this pathway is the hypusination of the eukaryotic initiation factor 5A (eIF5A), a unique post-translational modification in which the polyamine spermidine is covalently linked to a specific lysine residue, allowing cells to access a special subset of proteins that are crucial for autophagy, mitochondrial function, and immune cell fate. However, the extent to which the nutrition-polyamine axis regulates immune cell functionality in response to exogenous stimuli (e.g., vaccines, infections) has not been investigated. Therefore, this project aims to systematically dissect the role of the polyamine–hypusination axis in human immune cells under nutritional modulation, with a strong focus on clinical relevance and translational applicability.
Based at the Department of Gastroenterology, Infectious Diseases and Rheumatology at Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, our main clinical and research focus are inflammatory bowel diseases (IBD). Crohn’s disease (CD), one of the primary forms of IBD, exhibits various clinical phenotypes, including inflammatory (B1), stricturing (B2), and fistulizing (B3) disease phenotypes. We aim at understanding the biological differences between these phenotypes at the level of the mucosal microenvironment. With our large endoscopy unit and outpatient clinic, as well as gastroenterology ward, we have access to biological samples like intestinal biopsies along with the corresponding clinical data.
Our research project entitled “Identification of a gut microbiota signature in patients with drug-resistant epilepsy upon ketogenic diet treatment” aims to characterise the composition of the gut microbiota of patients affected by drug-resistant epilepsy undergoing ketogenic diet treatment, with the ultimate goal of developing probiotics as therapeutic tool. This research is characterised by combining both the clinical analysis of patients with epilepsy (encephalogram, NMRI, epigenetic changes and questionnaires on lifestyle and quality of life) and the molecular and cellular analysis of patients’ blood and stool. This project stands out for its strong clinical and experimental approach in close collaboration with the Clinic for Paediatrics and Neurology, Charité. The successful candidate will benefit from a training in which he/she will be able to put into practice his/her knowledge of the medical field and learn concepts, techniques and strategies of experimental research in the laboratory, paving the way to better understand how we could modulate the course of epilepsy via microbiota-diet modulation.
Within the framework of the graduate college “Re-Thinking Health,” our goal is to deepen our understanding of how the innate immune system contributes to both the maintenance of health and the development of chronic inflammatory diseases. While persistent immune memory is essential for long-term protection against infections, it can also hinder therapeutic success in chronic inflammatory conditions. Traditionally associated with the adaptive immune system, immune memory has recently been observed in innate lymphoid cells (ILCs), particularly Natural killer (NK) cells. However, the mechanisms underlying the establishment and maintenance of NK cell memory, as well as its functional consequences for health and disease, remain only partially understood. By investigating ILC and NK cell responses to viral infections and chronic inflammatory environments, we aim to uncover the extrinsic signals, intrinsic cellular characteristics, and molecular networks that drive memory formation and persistence. This integrative approach will not only expand our understanding of innate immune memory but may also reveal actionable targets to counteract pathological memory or harness memory persistence for improved cell-based therapies.
Based at the Department of Gastroenterology, Infectious Diseases and Rheumatology at Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin and at the Max Delbrück Center (MDC) in Berlin, our main clinical and research focus are chronic inflammatory diseases like Inflammatory bowel diseases (IBD). Crohn’s disease (CD), one of the main forms of IBD, has different clinical phenotypes, including an inflammatory (B1) as well as a stricturing (B2) disease phenotype, in which patients develop fibrotic stenoses of the intestine. Developing a molecular understanding of why some patients suffer from the formation of fibrotic strictures, while others do not, is still not understood. By investigating the mucosal microenvironment, we aim to establish a holistic understanding of the process of fibrotic stricture formation in CD to find answers to the driving question: ‘Stricturing in Crohn’s disease – what are the drivers in the mucosal microenvironment?’
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 mucocilary 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.1,2 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.3,4 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 activity5 and may thereby also have an effect on mucus properties and mucociliary clearance.
Pulmonary arterial hypertension is a cardiopulmonary disease that is characterized by profound remodeling of the pulmonary vascular tree and has a poor prognosis if left untreated. Current therapeutic approaches rely on vasodilatory drugs and do not address the underlying cause of vascular remodeling. Investigating the pathophysiology of pulmonary arterial hypertension on a novel, in vitro microvasculature-on-chip model allows to track changes of the vascular system and the dynamics of individual cell types specifically in a temporal and spatial context that was not possible before. As such, microvasculature-on-chip models – in combination with advanced imaging modalities, state-of-the-art transcriptomic and proteomic analyses, and functional read-outs – open up unprecedented avenues for the discovery of new disease mechanisms and therapeutic targets.
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.
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.
We are interested in the interaction of endothelial cells and their mesenchymal neighboring cells with immune cells in perivascular tissue areas called fibrovascular niches. These represent crucial strategic sites for resident immune cells regulating tissue homeostasis and maintain structural and functional integrity of blood vessels in health and disease. Factors disturbing structural and functional integrity of fibrovascular niches are associated with pre-mature aging and irreversible organ damage. However, the cellular interplay and molecular basis of those processes are not well understood.
Our lab studies the role of immune cells and inflammatory processes in the liver. During homeostasis the liver plays an important role in adaptation to environmental influences as it is constantly exposed to antigens from the gastrointestinal system, and plays a critical role in maintaining a balance between tolerance to harmless antigens (eg. food proteins or commensal bacteria) and control of pathogens.1 When this balance is disrupted (termed maladaptation) the resulting immune-mediated changes can lead to chronic liver diseases and ultimately cancer.2 Infiltration and activation of immune cells play an important role during the development of liver diseases, but the exact molecular and cellular mechanisms leading to the development of liver inflammation have not been fully elucidated until now. We are exploring the inflammatory processes during acute liver failure, metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD/MASH), liver cirrhosis and liver cancer in order to develop new diagnostic and therapeutic strategies. Furthermore, a better understanding of how both pro- and anti-inflammatory pathways can disrupt the homeostatic processes of a healthy liver is critical for the prevention of liver diseases in the first place.
Not Everything Is “Genetic”, but Genes Are Involved in Everything (adapted from Kenneth M. Weiss). Our group is interested in identification and investigation of genetic, clinical, and environmental factors determining onset of chronic kidney disease (CKD) and kidney survival. We make use of next-generation sequencing techniques and deep-phenotyping to identify genetic variants that are predictive for disease progression or convey protection from organ failure. We functionally evaluate identified germline variants in vitro in order to understand underlying molecular mechanisms leading to CKD on the one hand or protecting from kidney failure on the other. By doing so, we aim at defining and targeting molecular switches responsible for health maintenance and disease alleviation.