A hallmark of adaptive immunity is the clonal selection and expansion of cells with somatically diversified receptors and their long-term maintenance as memory cells. The innate immune system, in contrast, is wired to rapidly respond to pathogens via a broad set of germline-encoded receptors, acquiring epigenetic imprinting at the population level. One exception to this paradigm are Natural Killer (NK) cells, which can undergo specific expansion in response to murine and human Cytomegalovirus (CMV), raising conceptual parallels to adaptive immunity.1-3 In our more recent work, we have applied a single-cell multi-omic approach and leverage lineage tracing of human NK cells using mitochondrial mutations as endogenous barcodes4 to study clonality within the innate immune system and track NK cell memory to HCMV infection ex vivo. We have shown for the first time that HCMV induces the drastic expansion and differentiation of NK cell clones expressing the HCMV-specific receptor NKG2C,5 supporting a novel immunological paradigm of innate clonality.6
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.
Vaccines constitute one of the most effective public health interventions and play a crucial role in the control and prevention of infectious diseases. Their value to human health was recently demonstrated during the COVID-19 pandemic, when the rollout of vaccines played a pivotal role in lowering the case-fatality and thus ending the pandemic state.2 The versatility of vaccines is evident not only in their widespread use for prevention of disease from infections, but they can also lower morbidity and mortality from non-communicable diseases, such as myocardial infarction. Moreover, vaccines are explored as promising immunotherapeutics against cancer. Hence, the purposeful induction of protective immunity by means of vaccination has been shown to preserve health and to prevent disease.
Based in the Department of Gastroenterology, Infectious Diseases and Rheumatology, our main clinical and research focus is the field of Inflammatory bowel diseases (IBD). Within the treatment of IBD, therapeutic goals have evolved from a control of symptoms to mucosal healing, with deep remission (clinical remission, biomarker remission and mucosal healing) being the ultimate treatment goal.1 Developing a molecular understanding of deep remission is one of our main interests. By investigating states of deep remission – achieved through different treatment approaches – we aim to establish a holistic understanding of disease control in IBD to find answers to the driving question: ‘How healthy is a IBD patient in deep remission?’
The gastrointestinal mucosa consists of epithelial cells and a variety of surrounding stromal and immune cells. These cells act in concert to fulfill the functions of the mucosa such as nutrient absorption as well as the first line of defense against environmental threats. As one of the most prevalent immune cell types in the gut tissue, macrophages maintain mucosal barrier integrity. In addition to their role in immune defense, subsets of tissue-resident macrophages have been suggested to directly support functions of the epithelium as well as the vasculature and enteric neurons.1,2 Our research aims to understand the interplay between the epithelium, stroma, and macrophages. We would like to understand how gut resident macrophages support mucosal homeostasis and how the epithelium and stroma in turn nourish macrophages. To address this, we are now developing new organoid and assembloid models to recapitulate the cellular networks observed in vivo.
We are interested in understanding the role of the macrophages that reside within the kidney, termed kidney-resident macrophages (krMΦs). Although krMΦs are fundamental for kidney homeostasis, it is unclear how they support normal renal function and renal homeostasis. We seek to unravel the underlying mechanisms of how krMΦs mediate kidney resilience at steady state and in inflammation.
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.
Tissue resident immune cells maintain organ health by mechanisms that are not well understood. We propose to explore the mechanisms by which ILC crosstalk with resident macrophages to maintain homeostasis in the kidney.
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.
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 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.