A5020486321- PARP inhibition in cancer therapy
- Pancreatic function and diabetes
- DNA Repair Mechanisms
- MicroRNA in disease regulation
- Adipose Tissue and Metabolism
- Dietary Effects on Health
- Cell death mechanisms and regulation
- Sirtuins and Resveratrol in Medicine
- Immune Cell Function and Interaction
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Virus-based gene therapy research
- RNA modifications and cancer
- Diabetes and associated disorders
- Regulation of Appetite and Obesity
- Adipokines, Inflammation, and Metabolic Diseases
- Toxin Mechanisms and Immunotoxins
- NF-κB Signaling Pathways
- Circular RNAs in diseases
- Lipid metabolism and disorders
- COVID-19 Clinical Research Studies
- Immune cells in cancer
- Diabetes Management and Research
- interferon and immune responses
- S100 Proteins and Annexins
Helmholtz Zentrum München
2021-2025
University of British Columbia
2013-2021
Ludwig-Maximilians-Universität München
2021
German Center for Diabetes Research
2020
University Hospital Heidelberg
2019-2020
Heidelberg University
2019-2020
Technical University of Munich
2019
University of Zurich
2010-2017
Life Science Zurich
2010-2012
Czech Academy of Sciences, Institute of Physiology
2012
NF-κB regulates the expression of a large number target genes involved in immune and inflammatory response, apoptosis, cell proliferation, differentiation survival. In this study, we identified SIRT2 as deacetylase transcription factor p65. is member family sirtuins, which are NAD+-dependent deacetylases several cellular processes. interacts with p65 cytoplasm deacetylates vitro vivo at Lys310. Moreover, hyperacetylated Lys310 Sirt2−/− cells after TNFα stimulation, results increase subset...
The bone marrow in the skull is important for shaping immune responses brain and meninges, but its molecular makeup among bones relevance human diseases remain unclear. Here, we show that mouse has most distinct transcriptomic profile compared with other states of health injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals distinct, differentially expressed neutrophil-related pathways unique synaptic protein signature. 3D imaging demonstrates...
Type 1 diabetes is a progressive autoimmune disease that largely silent in its initial stages. Yet, sensitive methods for detection of β-cell death and prediction prevention are lacking. Micro-RNAs (miRNAs) have been found at high concentrations body fluids. Here this study we sought to determine whether an islet enriched miRNA, miR-375, suitable blood marker detect predict mice. We measured miR-375 levels by quantitative RT-PCR plasma samples streptozotocin (STZ)-treated C57BL/6 mice...
Human embryonic stem cells (hESCs) were used as a model system of human pancreas development to study characteristics the polyhormonal that arise during fetal development. HESCs differentiated into fetal-like pancreatic in vitro using 33-day, 7-stage protocol. Cultures ~90-95% PDX1-positive by day (d) 11 and 70-75% NKX6.1-positive d17. Polyhormonal scattered at d17, but developed islet-like clusters expressed key transcription factors d33. C-peptide glucagon secretion first detected d17...
Type 1 diabetes (T1D) is an autoimmune disease that clinically silent until the majority of β cells are destroyed. There unmet need for reliable and cost-effective biomarkers to predict diagnose at early stage. A number stable microRNAs (miRNAs) have been reported in serum plasma now being investigated as different diseases. We measured levels 745 miRNAs sera children with recent-onset T1D age-matched controls using locked nucleic acid-enhanced (LNA-enhanced) quantitative PCR profiling....
Pluripotent human embryonic stem cells (hESCs) are a potential source of transplantable for treating patients with diabetes. To investigate the impact host recipient on hESC-derived pancreatic progenitor cell maturation, were transplanted into immunodeficient SCID-beige mice or nude rats. Following transplant, basal C-peptide levels consistently higher in compared rats, but only rats showed robust meal- and glucose-responsive secretion by 19-21 weeks. Grafts from contained proportion...
Poly(ADP-ribose)polymerase-1 (PARP1) is a chromatin-associated enzyme that was described to affect chromatin compaction. Previous reports suggested dynamic modulation of the landscape during adipocyte differentiation. We thus hypothesized PARP1 plays an important transcriptional role in adipogenesis and metabolism therefore used development function as model elucidate molecular action obesity-related diseases. Our results show PARP1-dependent ADP-ribose polymer (PAR) formation increases and,...
Abstract Hypoxia-inducible factor 1 (HIF-1) is the key transcription regulating hypoxia-dependent gene expression. Lack of oxygen stabilizes HIF-1, which in turn modulates expression pattern to adapt cells hypoxic environment. Activation HIF-1 also detected most solid tumors and supports tumor growth through target genes that are involved processes like cell proliferation, energy metabolism, delivery. Poly(ADP-ribose) polymerase (PARP1) a chromatin-associated protein, was shown regulate...
ADP-ribosyltransferase Diphtheria toxinlike 1 [ARTD1; formerly called poly-ADP-ribose polymerase (PARP1)] is a chromatin-associated enzyme involved in regulating metabolic homeostasis. The liver at the core of glucose and lipid metabolism significantly affected by obesity syndrome. Here, we show that when fed high-fat diet (HFD), mice lacking ARTD1 developed exacerbated hepatic steatosis. ARTD1–/– had 19% higher weight than wild-type (WT) animals exhibited increased serum concentration...
One of the fastest cellular responses to genotoxic stress is formation poly(ADP-ribose) polymers (PAR) by poly(ADP-ribose)polymerase 1 (PARP1, or ARTD1). PARP1 and its enzymatic product PAR regulate diverse biological processes, such as DNA repair, chromatin remodeling, transcription cell death. However, inter-dependent function protein activity clouds mechanism underlying response. We generated a knock-in mouse model carrying point mutation in catalytic domain (D993A), which impairs...
Childhood obesity and early rapid growth increase the risk for type 2 diabetes. Such overnutrition can be modeled in mice by reducing litter size. We investigated effects of increased dietary fat intake on β cell function Swiss Webster mice. On a moderate-fat diet, accelerated weight gain induced hyperinsulinemia pups. Early males exhibited higher mass but reduced islet insulin content Pdx1 expression. Males had high diabetes incidence that was overnutrition, characterized progressive...
SUMMARY The meninges of the brain are an important component neuroinflammatory response. Diverse immune cells move from calvaria marrow into dura mater via recently discovered skull-meninges connections (SMCs). However, how bone is different other bones and whether it contributes to human diseases remain unknown. Using multi-omics approaches whole mouse transparency we reveal that highly heterogeneous across body. harbors most distinct molecular signature with hundreds differentially...
Abstract Although innate immunity is linked to metabolic health, the effect of leptin signaling in cells from immune system on glucose homeostasis has not been thoroughly investigated. We generated two mouse models using Cre-lox methodology determine myeloid cell-specific receptor ( Lepr ) reconstitution and knockdown vivo metabolism. Male mice with Lyz2Cre + loxTB/loxTB had better glycemic control as they aged compared male whole-body transcriptional blockade − ). In contrast, females only...
Summary Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on individual’s age unclear. Here, we investigated effects systemic metabolism and pancreatic islet function in old, middle-aged, young mice. Short-term improved glucose homeostasis across all groups, without altering morphology. In contrast, while chronic was beneficial for adult mice, it resulted impaired β-cell young. Using scRNAseq, delineated that...
Overconsumption of saturated fats promotes obesity and type 2 diabetes. Excess weight gain in early life may be particularly detrimental by promoting earlier diabetes onset potentially adversely affecting normal development. In the present study we investigated effects dietary fat composition on overnutrition-induced body glucose regulation Swiss Webster mice, which show susceptibility to high-fat diet-induced We compared homeostasis between a lard-based (HFL) diet, high fats, olive oil/fish...
Abstract Pancreas is a vital organ composed of exocrine and endocrine cells that aid digestion food regulate blood glucose levels. Perturbations in the function pancreatic leads to development life-burdening and/or threatening diseases such as diabetes cancer. Thus, it critical understand molecular check-points maintain normal pancreas physiology. MicroRNAs (miRNAs) are small non-coding RNAs involved regulating gene expression diseased tissues. Several miRNAs have tissue-specific patterns...
<div>Abstract<p>Hypoxia-inducible factor 1 (HIF-1) is the key transcription regulating hypoxia-dependent gene expression. Lack of oxygen stabilizes HIF-1, which in turn modulates expression pattern to adapt cells hypoxic environment. Activation HIF-1 also detected most solid tumors and supports tumor growth through target genes that are involved processes like cell proliferation, energy metabolism, delivery. Poly(ADP-ribose) polymerase (PARP1) a chromatin-associated protein, was...
<div>Abstract<p>Hypoxia-inducible factor 1 (HIF-1) is the key transcription regulating hypoxia-dependent gene expression. Lack of oxygen stabilizes HIF-1, which in turn modulates expression pattern to adapt cells hypoxic environment. Activation HIF-1 also detected most solid tumors and supports tumor growth through target genes that are involved processes like cell proliferation, energy metabolism, delivery. Poly(ADP-ribose) polymerase (PARP1) a chromatin-associated protein, was...
Supplementary Figure S1 from Poly(ADP-Ribose) Polymerase 1 Promotes Tumor Cell Survival by Coactivating Hypoxia-Inducible Factor-1–Dependent Gene Expression