Research Groups

The Section for Translational Surgical Oncology & Biobanking (STCOB) within the Department of Surgery focuses on protein expression profiles and the functional analysis of identified target proteins. We aim to understand cancer's molecular mechanisms and translate our findings into clinical routine for improved individualized diagnostic and therapeutic approaches. The Proteomics unit is one of the cornerstones of our infrastructure and is fully equipped with e.g., MALDI-MS/MS, Ion-mobility-LC-MS/MS, and Olink®. The SCTOB serves as the coordinating body for the BMBF-funded "MMAIC-IPMN" project, which focuses on the risk stratification of pancreatic cancer. Furthermore, the SCTOB leads the EMECK project, supported by the EU/WT.SH FIT program, and acts as a work package leader for "OUTLIVE-CRC" (BMBF). https://www.uksh.de/chirurgischeforschung-luebeck/

Our research group investigates underlying mechanisms of inflammation-driven diseases of the gastrointestinal tract such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Due to the re-mitigating chronic inflammatory processes, IBD patients have an increased risk of developing CRC. In this context, we defined the term Nutri-Inflammation to highlight the potential of nutrition to constantly promote intestinal inflammation and hence lifestyle-associated CRC. To understand how the gut responds to individual dietary habits on the molecular level in the context of IBD/CRC, we connect functional and metabolic data from cell biology with phenotypic and clinical data collected from human studies, intestinal 3D-organoid cultures or from animal models of acute or chronic intestinal inflammation as well as of inflammation-driven colorectal carcinogenesis. Our lab has long-standing experience in immunohistochemistry, fluorescence microscopy, live-cell imaging, flow cytometry, molecular cell biology, spatial single-cell proteomics / transcriptomics and metabolic analyses of intestinal cells.

Our research group is particularly interested in the interplay of inflammatory processes on the distribution and characteristics of peripheral blood monocyte subsets and monocyte derived macrophages. Monocytes are a major source of inflammatory mediators and important regulators of acute and chronic inflammatory diseases as well as of cancer development and progression. Our group consists of about 10 people including technicians, PhD, bachelor and master students and we are closely connected with other clinics and research groups on the campus in order to better understand the impact of distinct inflammatory and metabolic parameters on the monocyte associated individual immunologic situation.

Our research focuses on preclinical and clinical development of predictive and prognostic biomarkers in cancer using clinical cohorts and informative in-vitro and in-vivo models. We discovered genetic mechanisms of treatment resistance in CML, MPN, and AML. Our group established Liquid Biopsy analyses to predict treatment response in solid tumors, and to identify patients at risk for relapse after curative-intent surgery in lung cancer. We co-established Molecular Tumor Boards to clinical routine in Germany and developed the use of JAK1/2 inhibitors in GvHD. We investigate the significance of Mast cells and hereditary Tryptasemia (HaT) for mast cell mediated symptoms and anaphylaxis. We are currently focusing our research on the significance of inflammation for tumor progression and treatment resistance. For this purpose, we investigate cell-line and in vivo models and examine inflammatory cytokines, immune cell infiltration, ER-stress signalling, ER-phagy and mutations involved in clonal haematopoiesis.

Our immunology laboratory is interested in the development and function of antibody (Ab) compositions consisting of different isotypes, subclasses and glycosylation patterns. The idea is that the induced Ab composition determines fighting or non-fighting Ab responses against pathogens and cancer, or pathogenic and non-pathogenic Ab responses in the context of inflammatory (auto)immune diseases and allergies. Patients with inflammatory (auto)immune diseases often begin to express IgG (auto)antibodies (autoAbs) years before they develop overt clinical disease (pre-disease stage). In addition, healthy individuals may express IgG autoAbs in the absence of disease symptoms. There is a correlation between the switch of the (auto)antigen-specific and total blood IgG Fc glycosylation pattern to more non-(a)-galactosylated forms prior to the development of an inflammatory (auto)immune disease. Accordingly, agalactosylated IgG Abs have been associated with inflammatory functions, whereas galactosylated plus terminal sialylated IgG Abs have less inflammatory or anti-inflammatory properties. Total IgG glycosylation acts as a vast immunological buffer system, controlling the expression levels of activating and inhibitory immune receptors. Consistently, the level of total IgG galactosylation and sialylation in the blood is used as a biomarker for the inflammatory immune status (biological age) of an individual. We have projects in the field of inflammatory autoimmunity, allergy, vaccination, cancer and nutrition to investigate T and B cell subsets and Ab compositions and their function. A healthy diet may increase both the level of total and (auto-)antigen-specific blood IgG galactosylation and sialylation, thereby improving the biological age as well as inflammatory (auto-)immune symptoms. In the context of meta-inflammation, we are investigating the relationship between diet, microbiome, blood fatty acids and genetics with the development or inhibition of inflammatory immune responses. Our Laboratory of Antibody Glycan Analysis has developed techniques to generate monoclonal Abs, detect Ab compositions and modify and measure Ab glycosylation. For more information on projects, please refer to the publication lists in Scopus (7102012162) or ORCID (0000-0002-5383-8603).

Prof. Joanne Trinh's heads the "Integrative omics in Parkinson's disease" research group. Her focus is on identifying factors related to the pathogenesis of Parkinson's disease. One of her projects is on the interaction of the mitochondria, microbiome and metabolome. She has discovered mitochondrial genetic modifiers of disease onset for monogenic forms of Parkinson's and aims to dive deeper into the mechanisms of such modifiers. Another project is on Covid and how it affects Parkinson's disease using single-cell transcriptomics to investigate inflammation.

My group is interested in regulating cerebral blood flow at the blood-brain barrier (BBB) and in the distinct roles of the involved cell types. The BBB is formed by vessels and consists of the basement membrane and cells, which have special properties leading to a very tight and highly organized structure at the interface between blood and brain. In a healthy brain, the BBB prevents neural tissue from the invasion of pathogens, the infiltration of immune cells and extravasation of serum proteins. In addition, brain cells have a high demand for glucose, oxygen, and other factors, coming from the blood. The perfusion with blood is tightly regulated in terms of time and localization. In this process, different cell types, including neurons, astrocytes, pericytes, smooth muscle cells, and endothelial cells, are activated and can influence the kinetics and amplitude of perfusion. If the communication between these cells is dysregulated as in stroke, dementia, diabetes, or obesity, also vascular reactivity is altered. We are interested in intercellular connections, especially in those that involve endothelial cells, and in the effects of endothelial dysfunction on related brain functions. For this purpose, we are using state-of-the-art technologies like two-photon microscopy, tissue-specific knockout animal models, and virus-mediated gene transfer. Since the cerebral vasculature is highly affected by metabolic diseases, which are accompanied by inflammatory alterations such as obesity and diabetes, we are working at the interface between metabolic, inflammatory, and vascular pathologies, focused on the brain.

Our group is interested in the physiological role of tanycytes, a specialized population of glial cells in the ependymal layer of the third ventricle. The cell bodies of tanycytes contact the cerebrospinal fluid (CSF) and send long projections into the parenchyma of the basal hypothalamus and the median eminence, where they make contact with blood vessels. Tanycytes are strategically positioned to control the blood-CSF barrier of the median eminence, regulate the transport of substances across this barrier, and influence hormone release into the portal venous system of the median eminence. In recent years, we have contributed to further elucidating the physiological functions of this cell type. Our main focus is to clarify the role of tanycytes in regulating energy homeostasis, barrier function, and their influence on hormone release in the hypothalamus-pituitary axis. Certain pathologies, such as inflammation, autoimmunity, and changes in the thyroid axis, influence these properties. To investigate these topics, we have developed new genetic and viral tools to specifically manipulate the functions of tanycytes in vivo. With these tools, we can knock out or overexpress genes specifically in tanycytes and examine the structural and genetic consequences, as well as changes in the animals' phenotype. For these purposes, we primarily use various mouse models, which are analyzed using methods such as indirect calorimetry, behavioral tests, hormonal assays, and gene expression analyses.

Prof. Henriette Kirchner is a nutrition scientist by training focuses on metabolic diseases. She received her PhD from the Universities of Potsdam and Cincinnati in 2011 where she discovered with Prof. Matthias Tschöp that ghrelin is rather a meal preparatory signal than the hunger homone. Moreover, she helped to develop the first dual-incretins and established mouse models of metabolic surgery. In 2011 Prof. Kirchner moved to Stockholm for her post-doctoral studies in Juleen Zierath’s lab at the Karolinska Institute funded by a prestigious EMBO longterm fellowship. Still focusing on metabolic diseases she identified epigenetic patterns in liver, muscle and adipose tissue that contribute to the development obesity and type 2 diabetes. Funded by the Emmy-Noether Program she returned to Germany in 2014 and joined the Center of Brain Behavior and Metabolism (CBBM) at the University of Lübeck where she currently leads the Epigenetics & Metabolism lab with the aim to develop novel epigenetic therapies for metabolic diseases. Beginning of 2024 she was awarded one of four professorships of excellence from the State of Schleswig-Holstein, Germany.

To study disease mechanisms in a biologically relevant cell system, we provide a platform for collaborative projects using the technology of induced pluripotent stem cells (iPSCs) (https://www.stemcells-luebeck.de). These iPSCs are generated by reprogramming of patientspecific cells and differentiated into the diseased cell type. We collaborate with several national and international colleagues. Over the past 15 years, we have built up a biobank of >300 iPSC lines and developed differentiation protocols into different subtypes of neurons, astrocytes, microglia, macrophages, and cardiomyocytes to elucidate disease mechanisms. Our focus within the EKF MSG International PhD Program will be the crosstalk between different brain cells leading to neuroinflammation. To investigate neuroinflammation in Parkinson’s disease, we recently generated a human cellular model by differentiating iPSCs into dopaminergic neurons and microglia. We combined these cells in co-culture to perform cytokine profiling. We found a strong co-culture-specific response to IL-1β treatment, indicating a unique microenvironment created by dopaminergic neurons and microglia. Moreover, we detected protein level changes in genes associated with Parkinson’s disease upon inflammatory stress in microglia. We aim to further investigate the mechanisms leading to neuroinflammation in our cell models by multimodal analyses, including single-cell sequencing, proteomics, and metabolomics to resolve impaired cell states and identify previously unreported cellular crosstalk.

The JAK2V617F mutation is a major driver of myeloproliferative neoplasms (MPNs), which include PV (Polycythemia Vera), ET (Essential Thrombocythemia) and PMF (Primary Myelofibrosis). JAK2 inhibitors, such as ruxolitinib, show remarkable clinical activity in MPN patients regardless of JAK2 mutation status, and several clinical studies suggest that ruxolitinib is symptom controlling but not curative. The most devastating complication of chronic MPNs is transformation to secondary AML (sAML), and then the disease is aggressive, and other than allogeneic stem cell transplantation, there is no reliable alternative therapy for MPN patients. Recent data suggest that accumulation of driver gene mutations and its transcriptional phenotype such as induction of “inflammatory pathway” creates the fertile soil for MPN progression. However, the origin and spread of inflammation to different organs in MPN is poorly understood in context of metabolism. Several studies highlight the role of the metabolic diet in reduction of inflammation. So, we decided to understand the epigenetic changes associated with metabolism in order to suppress the inflammation in MPN diseases.

The focus of my research group is on utilizing preclinical models to develop new therapeutic approaches and translate them into clinical trials—fully in line with the principles of precision oncology. We generate hypotheses based on data on gene expression changes and mutational analyses from various oncological studies (AML, MDS, multiple myeloma), as well as from the molecular tumor board datasets of the Center for Personalized Medicine (ZPM), where I serve as campus-wide co-director. The objective is to link clinical data with multi-omic analyses (RNA-Seq, metabolic, and radiological data) in order to develop predictive models and derive individualized treatment strategies. A particular emphasis lies on investigating the interplay between epigenetic, metabolic, and DNA repair alterations in the tumor and the surrounding tissue.

The research group led by Prof. Stefan Borgwardt at the Center for Integrative Psychiatry takes an interdisciplinary approach, focusing on the biological mechanisms of mental illnesses, particularly in the context of metabolic inflammation (metaflammation). A key focus is on the role of inflammatory processes in the brain and their interaction with metabolic factors, which can influence both the development and progression of psychiatric disorders such as schizophrenia and affective disorders. His work combines modern neuroimmunological methods with imaging, psychophysiological, and clinical approaches to decipher the underlying biological mechanisms and identify potential therapeutic targets. Since 2018, Prof. Borgwardt has been recognized annually as one of the "most influential" and "Top 1% most cited scientists in the field of psychiatry/psychology" by Clarivate/Web of Science (https://hcr.clarivate.com). The connection to metaflammation lies in our focus on investigating the link between early chronic inflammatory processes in the brain and mental illnesses. Our goal is to develop new biomarker-based approaches for the early diagnosis and treatment of psychiatric disorders, based on the mechanisms of metaflammation.

The Experimental and Translational Hepatology and Hepatobiliary Oncology research group focuses on the study of acute and chronic liver diseases, liver cirrhosis, and their complications. Key aspects include molecular, metabolic, and immunological aspects of chronic liver diseases, ranging from autoimmunity to fibrogenesis and portal hypertension, tumor development, and tumor progression. The goal of the research is to identify novel diagnostic and therapeutic approaches. To this end, the group utilizes cutting-edge technologies, such as next-generation sequencing and bioinformatics concepts, as well as integrative deep learning/artificial intelligence approaches. Cellular transplantation and representative animal models, as well as the use of CRISPR/Cas9 technology, support the investigation of pathophysiological mechanisms. Patient-specific cellular models also promote individualized therapeutic approaches through a so-called Living Tissue Biobank. The application of these models not only promotes new insights into hepatobiliary oncology but also extends from metabolic diseases to infections and chronic inflammation to tissue regeneration of the liver.

The primary research focus of my group is to unravel the intricate interactions between nutritional components, gastrointestinal tissues, and immune cells in gastrointestinal disorders such as Irritable Bowel Syndrome (IBS) and food hypersensitivities. Additionally, we aim to elucidate the role of granulocytes in the inflammatory processes underlying metabolic disorders, including obesity, diabetes, and non-alcoholic steatohepatitis (NASH) with a University of Lübeck funded project (SPP Metainflammation). Our expertise lies primarily in the non-classical immunological functions of eosinophils, complement activation, and anaphylatoxin signaling in such contexts. As part of the Institute for Nutritional Medicine, led by Director Christian Sina, our group maintains close collaborations with the Molecular Gastroenterology team, headed by Prof. Derer, fostering a dynamic and stimulating research environment. Moreover, our institute is equipped with cutting-edge high-throughput technologies, including a CosMX spatial melecular imager, enhancing our ability to conduct advanced molecular investigations.

My research in Clinical Endocrinology, Diabetes & Metabolism is dedicated to the investigation of metabolic disorders, with a particular emphasis on obesity and type 2 diabetes (T2D). My work delves into the mechanisms driving metabolic disease and related complications with a focus on e.g. the role of sleep, circadian rhythms, and meal timing while exploring innovative therapeutic approaches. A crucial aspect of my research involves identifying predictors of effective weight loss in patients undergoing lifestyle interventions, pharmacotherapy (GLP - 1RA, GLP - 1/GIP), or bariatric surgery, and assessing their impact on complications such as obstructive sleep apnea (OSA), metabolic dysfunction - associated steatotic liver disease (MASLD), and retinal changes. Moreover, my work investigates chronic inflammation and immune dysregulation in obesity and T2D, aiming to develop targeted therapies for these conditions . My working group employs state - of - the - art methods for metabolic phenotyping in clinical research, including hyperinsulinemic clamp studies, body composition analysis by MRI and DEXA scan, whole - body plethysmography, and actigraphy. In collaboration with the Department of Ophthalmology, my studies on choroidal thickness as a potential early biomarker for diabetic retinopathy, utilize high - resolution optical coherence tomography (OCT) and fluorescence lifetime imaging to characterize metabolic changes in the posterior structures of the eye.

Our group is a translational research group at the Department of Surgery. We focus on preclinical models of gastrointestinal tumors, i.e., pancreatic cancer to test treatment response ex vivo and facilitate personalized patient treatment. Underlying molecular mechanisms of treatment resistance in pancreatic cancer are poorly understood. There has been emerging evidence over the last few years that intratumoral heterogeneity (ITH) is a key determinant in tumor biology, treatment response and ultimately patient survival. We establish clonal models from patient-derived primary cell lines/ organoids and classical cell line models to evaluate clone-specific treatment response and its association with transcriptomic and proteomic profiles. The main focus of our work are organotypic slice cultures (OTSCs) as preclinical ex vivo model for the development of personalized treatment strategies. Most currently used preclinical models such as patient-derived cell lines/ organoids and xenografts lack the specific tumor microenvironment (TME) and therefore allow only limited response prediction. OTSCs of fresh tumor samples are a close approximation of the tumor in situ. They maintain their baseline morphology, proliferative activity and microenvironment during the cultivation for a defined, tissue-dependent period. We could show that distinct components of the immunological TME, including immune cell populations positive for CD3, CD4, CD8, CD68 and CD163, are consistently present in pancreatic cancer OTSCs. This technique enables us to evaluate treatment effects spatially-resolved in the specific preserved immunological/ inflammatory tissue context by downstream analyses of the transcriptome, proteome und metabolome. Individual patients are followed up closely in our clinical department. Ex vivo responses and molecular findings are correlated with treatment and survival of the respective patients.

Our research focuses on host-pathogen interactions, with a particular emphasis on human pathogenic Chlamydia trachomatis, the most common bacterial sexual transmitted diseases. The ability of the bacterium to adapt to environmental conditions, such as changes in oxygen levels and microbiota, is essential for infection establishment and intracellular survival. To better understand the pathogenicity of Chlamydia, we use multi omics approach in vitro, ex vivo organoids, and in vivo mouse models to elucidate the metabolic reprogramming of bacteria and mammalian cells during the course of infection under different microenvironments. The goal of our research is to translate basic research into clinical applications.

Our research investigates the immunological and oncological impacts of cigarette smoking, e - cigarettes, and heated tobacco products. We analyze their effects on inflammatory pathways, immune checkpoint molecules (e.g., PD - L1), monocyte activation, and cyto kine profiles. Utilizing in vitro and clinical studies, we explore the role of these nicotine delivery systems in thoracic oncology, particularly in lung cancer progression and immune modulation. By integrating molecular and translational approaches, our work aims to provide insights into smoking - /vaping - associated inflammation and its implications for cancer and cancer therapy.

Exposure to inhalative noxious substances is a driver of chronic inflammation leading to lung cancer. My group is interconnected with clinical and experimental research within the Department focusing on how metabolic and inflammatory reactions are ultimately leading to lung cancer. Within this context, my group is interested in loc al and systemic effects of the human microbiome. Thus, we perform holistic microbiome analyses on patients with a focus on modern nicotine delivery systems and other inhalable substances and we are engaging in experimental work, trying to dissect how the microbiome contributes to metabolic and inflammatory shifts in this context.