A5009952080- Adipokines, Inflammation, and Metabolic Diseases
- Air Quality and Health Impacts
- Diet and metabolism studies
- Liver Disease Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Diabetes and associated disorders
- Bariatric Surgery and Outcomes
- Gestational Diabetes Research and Management
- Energy and Environment Impacts
- Immune cells in cancer
- Birth, Development, and Health
- Gut microbiota and health
- Biomarkers in Disease Mechanisms
- Chronic Myeloid Leukemia Treatments
- Regulation of Appetite and Obesity
- Diet, Metabolism, and Disease
- Immune Cell Function and Interaction
- Dietary Effects on Health
- Body Contouring and Surgery
- Ubiquitin and proteasome pathways
- Heme Oxygenase-1 and Carbon Monoxide
- Extracellular vesicles in disease
- Photochromic and Fluorescence Chemistry
- Advanced Glycation End Products research
- Pharmacology and Obesity Treatment
University of California, San Diego
2022-2025
University of Basel
2017-2023
Goethe University Frankfurt
2023
University Hospital of Basel
2017-2022
While macrophage heterogeneity during metabolic dysfunction-associated steatohepatitis (MASH) has been described, the fate of these macrophages MASH regression is poorly understood. Comparing progression vs regression, we identified specific subpopulations that are critical for MASH/fibrosis resolution. We elucidated restorative pathways and gene signatures define regression-associated establish importance TREM2 + regression. Liver-resident Kupffer cells lost replaced by four distinct...
Chronic low-grade inflammation is a hallmark of obesity and associated with cardiovascular complications. However, it remains unclear where this starts. As the gut constantly exposed to food, microbiota, metabolites, we hypothesized that mucosal immunity triggers an innate inflammatory response in obesity. We characterized five distinct macrophage subpopulations (P1-P5) along gastrointestinal tract blood monocyte (classical, non-classical, intermediate), which replenish intestinal...
Abstract Aims/hypothesis Colony stimulating factor 1 (CSF1) promotes the proliferation, differentiation and survival of macrophages, which have been implicated in both beneficial detrimental effects on glucose metabolism. However, physiological role CSF1 signalling homeostasis potential therapeutic implications modulating this pathway are not known. We aimed to study composition tissue macrophages (and other immune cells) following receptor (CSF1R) inhibition elucidate metabolic consequences...
Abstract Background Air pollution has emerged as an unexpected risk factor for diabetes. However, the mechanism behind remains ill-defined. So far, lung been considered main target organ of air pollution. In contrast, gut received little scientific attention. Since particles can reach after mucociliary clearance from lungs and through contaminated food, our aim was to assess whether exposure deposition in or drive metabolic dysfunction mice. Methods To study effects versus exposure, we...
Abstract The obesity epidemic continues to worsen worldwide. However, the mechanisms initiating glucose dysregulation in remain poorly understood. We assessed role that colonic macrophage subpopulations play homeostasis mice fed a high-fat diet (HFD). Concurrent with intolerance, pro-inflammatory/monocyte-derived macrophages increased HFD. A link between numbers and glycemia was established by pharmacological dose-dependent ablation of macrophages. In particular, colon-specific depletion...
Abstract Immunotherapy profoundly impacted cancer treatments by harnessing the patient’s immune system. Phagocytosis, process whereby cells engulf and destroy foreign particles or cells, plays a critical role in tumour cell clearance. Herein, we introduce novel concept termed “ENPHASYS” – En hancement of Pha gocytic Sy napse s designed to direct amplify phagocytosis using heterobifunctional molecules named phagocytic synapse enhancers (PSEs). By engineering de novo PD-L1 binder linked...
Abstract Gestational diabetes mellitus (GDM) is one of the most common diseases associated with pregnancy, however, underlying mechanisms remain unclear. Based on well documented role inflammation in type 2 diabetes, aim was to investigate GDM. We established a mouse model for GDM basis its two major risk factors, obesity and aging. In these mice, we observed increased Interleukin-1β (IL-1β) expression uterus placenta along elevated circulating IL-1β concentrations compared normoglycemic...
Macrophages have been recognized as key players in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether pharmacological attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and anti-diabetic properties, how this impacts on NAFLD. We analyzed the pro- gene expression murine human monocytes vitro presence or absence imatinib. In a time-resolved study, we characterized metabolic manifestations such hepatic steatosis,...
Abstract Background We previously found that air pollution particles reaching the gastrointestinal tract elicit gut inflammation as shown by up-regulated gene expression of pro-inflammatory cytokines and monocyte/macrophage markers. This inflammatory response was associated with beta-cell dysfunction glucose intolerance. So far, it remains unclear whether changes upon oral exposure are causally linked to development diabetes. Hence, our aim assess role immune cells in mediating intolerance...
Abstract Fluorescent biosensors revolutionized biomedical science by enabling the direct measurement of signaling activities in living cells, yet current technology is limited resolution and dimensionality. Here, we introduce highly sensitive chemigenetic kinase activity that combine genetically encodable self-labeling protein tag HaloTag7 with bright far-red-emitting synthetic fluorophores. This enables five-color biosensor multiplexing, 4D imaging, functional super-resolution imaging via...
Introduction Increasing survival rates after hematopoietic stem cell transplantation (HSCT) in childhood should put focus on improving the quality of life as adults. An essential aspect is fertility and its preservation. In order to take advantage possibility preservation, counseling be provided patients their parents prior gonadotoxic therapies. Methods The aim this survey was analyze impact pediatric using questionnaires designed for study questions. Fifty-one 7 adolescent were interviewed...
Background: Chronic inflammation such as systemic or tissue has been well established in metabolic disease. Although macrophages thereby play a key role, not much is known about the initiation of inflammation. As gut makes up largest macrophage reservoir body and gastrointestinal changes occur disease (altered microbiota, increased endotoxin cytokines), aim our study was to assess role intestinal (iMϕs) obesity. Research Design Method: IMϕs were isolated from colon C57BL/6, germ-free CCR2-/-...
Abstract Aims Non-alcoholic fatty liver disease (NAFLD) has become one of the most common diseases worldwide. As macrophages play a key role in NAFLD, therapies targeting have been postulated. Indeed, strategies depleting or blocking monocyte recruitment into improve however, are not feasible clinical practice. Our goal was to assess whether attenuation can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and anti-diabetic properties, how this impacts NAFLD....
Background: Epidemiological studies show an association between air pollution and increased diabetes risk. However, the causal mechanism remains poorly understood. While it is believed that particles inhaled into lungs cause via local systemic inflammation, these also reach gastrointestinal (GI) tract by swallowing mucociliary clearance could thereby initiate diabetes. Research Design Method: To differentiate effects of reaching vs. GI tract, male C57B6/N mice were exposed to diesel exhaust...
Background: Besides classical risk factors such as sedentary lifestyle and unhealthy diet, air pollution has emerged an unexpected factor for type 2 diabetes. However, the causal mechanism remains poorly understood. Air particles are known to reach gastrointestinal tract by mucociliary clearance. Underlining clinical relevance of oral exposure, been associated with a variety diseases. Therefore, we aim study effects exposure on glucose metabolism potential immune-mediated mechanism. Research...
Air pollution has emerged as an unexpected risk factor for diabetes 1–6 . The mechanisms linking air and remain, however, unknown. It been postulated that lung exposure mediates via systemic inflammation insulin resistance 7–9 By contrast, gut to pollutants received little attention, even though a large proportion of particles are swallowed after mucociliary clearance from the upper airways 10 Here, we identified intestinal macrophages key mediators with impaired beta-cell function. Upon...