Chronic liver disease is among the most prevalent causes of organ failure and death worldwide, yet the molecular and cellular mechanisms that drive its progression remain incompletely understood and are driven by different etiologies. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD) account for the majority of cases with liver cirrhosis in Germany. Our group investigates how the hepatic immune microenvironment is reshaped during chronic inflammation, with a particular focus on the spatial organization of innate immune cells. Kupffer cells and monocyte-derived macrophages occupy defined tissue niches within the liver, and their function is strongly influenced by the local molecular environment. Similarly, B cells accumulate in diseased liver tissue and produce immunoglobulin, however this relationship in the pathogenesis of chronic liver disease remains unexplored.
This project sits at the heart of the Re-Thinking Health mission: by mapping the spatial protein landscape of the inflamed and fibrotic liver and linking it to the real-time behavior of immune cells, we aim to define the molecular hallmarks that distinguish healthy from diseased hepatic tissue neighborhoods. The findings will provide a foundation for understanding how immune dysregulation is spatially organized – and how it might be interrupted to preserve or restore liver health.
This project addresses a central aim of the EKFS Graduate School: to identify systemic signals that precede, accompany, and potentially predict age-related disease. Rather than studying one organ in isolation, the unbiased ageing-health project asks whether a measurable low-grade inflammatory state in blood marks broader multimorbidity in ageing. By linking ultra-sensitive circulating inflammatory profiles to visible, metabolic, neoplastic, ocular, and microbiome-associated ageing phenotypes in mice, the study fits the prevention focus of EKFS and can nominate biomarker signatures relevant to early risk stratification in humans.
***Follows.
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.
Within the graduate college, this project addresses how systemic sulfate homeostasis influences drug-induced liver injury. By studying the role of SLC26A1 in acetaminophen toxicity, it links renal and hepatic physiology with translational and population-based approaches. The integration of mouse models and human biobank data aligns with the program’s goal of bridging basic and clinical research to identify mechanisms and risk factors of acute liver failure.
We are interested in understanding the mechanisms by which a specific subset of innate lymphocytes, namely group 3 innate lymphoid cells (ILC3), regulate immune responses and tissue functions at homeostasis and in cancer. ILC3 are tissue-resident cells located at barrier tissues which occupy specific tissue niches where they constantly produce cytokines, particularly IL-22. ILC3-derived IL-22 maintains the integrity of epithelial surfaces and regulates cell processes involved in epithelial cell malignant transformation. However, the role of ILC3 and IL-22 in vascular remodeling and angiogenesis, which is a key step in tumorigenesis and a hallmark of cancer, remains largely unexplored. We seek to systematically investigate the role of ILC3 in the regulation of endothelial cell development and function in homeostasis and during tumor evolution to identify new therapeutic targets.
The project addresses the “Re-Thinking Health” concept by focusing on the molecular mechanisms that actively maintain a healthy, stable cellular identity. The dynamic balance of GATA-3’s nuclear import and degradation is a prime example of a health-preserving signalling network (Saikali et al., Cell Rep. 2026). By understanding how this rheostat is finely tuned, we can define the molecular signature of a healthy immune state, providing a critical foundation for recognizing the earliest deviations toward maladaptive, inflammatory conditions and identifying novel targets for prevention.
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.
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?’
Health is not merely the absence of disease, but a dynamic, active molecular process where the development and preservation of a competent immune system is crucial. A core characteristic of immunological health is thymopoiesis. Impaired development or decay of thymopoietic capacity shorten the health span through increased susceptibility to infectious diseases, cancer, autoimmunity, and inflammatory disorders.1,2 To extend the human health span, we need to define the homeostatic pathways that actively enable and preserve immunological health. Still, crucial signaling pathways governing T-cell development in the thymus are insufficiently characterized on the molecular level in humans. Such insights are important for the early detection of deviations from health for diagnostic purposes and for the development of intervention strategies to re-establish healthy thymopoiesis.1,3 Our laboratory investigates the epigenetic regulatory mechanisms in immune cells, which have to react particularly flexibly to external influences (differentiation cues, infection, inflammation, microbiota, etc.). We profile genome-wide epigenetic structures to identify key elements that make a decisive contribution to the generation and function of immune cells during health and in situations of misguided immune reactions (e.g. chronic inflammation and autoimmunity). These elements will help to clarify the molecular reasons for misregulated immune reactions and might represent promising therapeutic targets. Furthermore, in situation where immune cells serve as therapeutic agents to regain health (advanced therapy medicinal products, ATMPs, such as adoptive cell therapy) epigenetic structures may be used as biomarkers for quality and safety control purposes, and also as molecular switches for gene expression (‘epigenetic editing’), which may equip cell products with desired characteristics.
We study the development and function of the innate immune system, with a particular emphasis on innate lymphoid cells (ILC). Our current goal is to achieve a molecular-level understanding of how the innate immune system integrates environmental cues (such as those derived from nutrients, microbiota, and circadian rhythm) to influence tissue physiology. Recent findings have uncovered increasingly complex interactions between components of the innate immune system and fundamental developmental and biological processes, pointing to previously unrecognized pathways through which immune mechanisms may be harnessed to enhance health and longevity. These insights suggest expanded roles for the immune system in regulating tissue homeostasis, morphogenesis, metabolism, regeneration, and growth. Our work is inherently interdisciplinary, bridging fields such as immunology, microbiology, epigenetics, developmental and stem cell biology, nutrition science, tumor biology, and regenerative medicine.
Disease prevention is taking a central role in tackling the burden of cardiovascular disease in our aging society. Thrombotic cardiovascular diseases such as venous thromboembolism, stroke and myocardial infarction are main drivers of morbidity and mortality worldwide. A central pathomechanism in these thrombotic cardiovascular diseases is termed thromboinflammation and arises from a deleterious dysregulation of an evolutionary conserved host defence mechanism involving platelets, the innate immune and coagulation system. There is an unmet clinical need for a better mechanistical understanding of thromboinflammation, in order to novel regulatory mechanisms that may pave the way for potential therapeutics, biomarkers and preventive measures. By pursuing this aim we established a across species approach to investigate the paradox that long-term immobility during hibernation in brown bears and patients with spinal cord injury (SCI) does not increase the risk of thrombosis. Our research acts at the interface between immunology, cardiovascular science and preventive medicine by taking advantage of an interdisciplinary translational research approach.
Hospital-acquired infections remain one of the most pressing unresolved challenges in critical care, yet the role of nutritional support, ubiquitous in ICU management, in shaping host susceptibility through microbiota and mucosal immune perturbations has been systematically overlooked. This project offers a doctoral candidate the opportunity to investigate this clinically urgent and mechanistically underexplored question using state-of-the-art approaches spanning gnotobiotic mouse models, microbiome profiling, intestinal organoid culture, and transcriptional analyses of epithelial cells.
The scientific focus of our lab within the framework of the graduate college centers on unraveling the multifaceted role of clonal hematopoiesis (CH) in disease prevention and inflammatory processes. CH is recognized as a pre-malignant condition that significantly increases the risk of hematologic malignancies. Beyond its oncogenic potential, CH has emerged as a critical risk factor for cardiovascular diseases such as stroke, myocardial infarction, and atherosclerosis, contributing to both initial and recurrent events. Moreover, CH is intricately linked to chronic inflammation, functioning both as a driver and a consequence of sustained immune dysregulation. By investigating these complex interconnections, our research aims to deepen the understanding of CH as a central node in disease pathogenesis and to identify novel strategies for early intervention and prevention.
Our project directly aligns with the central mission of the Else Kröner-Fresenius Graduate College Re-Thinking Health, which aims to establish a novel, mechanistic understanding of health as an active, regulated biological state and to identify molecular targets for prevention. Rather than focusing solely on disease mechanisms, the project investigates how immune-mediated signaling pathways contribute to the maintenance of neuronal integrity and functional resilience in the central nervous system. Specifically, this project addresses the role of Interleukin-12 (IL-12) signaling in neurons and glial cells in the context of aging and neurodegeneration. By dissecting the cell type-specific functions of the IL-12 receptor, particularly in Parvalbumin-positive interneurons, the study explores whether immune-derived signals contribute to adaptive, health-preserving processes in the brain. This approach reflects the Graduate College’s conceptual framework that health is maintained by distinct molecular pathways, including those mediating adaptation to environmental and internal stressors.
Importantly, the project integrates both human and murine data to identify molecular signatures associated with resilient versus maladaptive neuroinflammatory responses. In doing so, it contributes to defining early deviations from a healthy state, a key objective of the program. Furthermore, by identifying cell-specific signaling mechanisms that modulate neuronal survival, network stability, and myelination, the project may uncover novel molecular targets for preventive strategies in age-associated neurodegenerative diseases such as Alzheimer’s disease.
Overall, this work exemplifies the transition from a disease-centered to a health-centered research paradigm by investigating how immune-neuronal interactions shape brain health, resilience, and the prevention of neurodegenerative pathology.
The innate immune system develops early in parallel with tissue formation, suggesting its role extends beyond host defense. In particular, tissue-resident innate lymphoid cells (ILCs) colonize tissues during fetal life and acquire effector functions prenatally acting as early-life sensors of the tissue environment. Our research focuses on understanding how the immune system, and ILCs in particular, contribute to the active maintenance of tissue homeostasis and how tissue-derived signals shape ILC differentiation, maintenance, and function. By defining these pathways, we aim to understand the molecular transition from a state of health to the earliest stages of pathology.