A5058826920- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Renal cell carcinoma treatment
- Acute Myeloid Leukemia Research
- Renal and related cancers
- Hops Chemistry and Applications
- Protein Degradation and Inhibitors
- Fermentation and Sensory Analysis
- Acute Ischemic Stroke Management
- Mitochondrial Function and Pathology
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Cardiac Imaging and Diagnostics
- Cancer Research and Treatments
- Immune Response and Inflammation
- Chronic Lymphocytic Leukemia Research
- Ferroptosis and cancer prognosis
- Endoplasmic Reticulum Stress and Disease
- Cerebrovascular and Carotid Artery Diseases
- FOXO transcription factor regulation
- Coronary Interventions and Diagnostics
- Cardiac, Anesthesia and Surgical Outcomes
- Acute Lymphoblastic Leukemia research
- NF-κB Signaling Pathways
- Animal and Plant Science Education
Medizinische Hochschule Hannover
2024-2025
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2021-2025
University Hospital Cologne
2022-2025
University Hospital Heidelberg
2021-2025
Heidelberg University
2021-2025
University of Cologne
2018-2025
University of Cambridge
2018-2024
Hutchison/MRC Research Centre
2018-2024
Medical Research Council
2018-2024
Heidelberg University
2024
Targeted immunotherapy in acute myeloid leukemia (AML) is challenged by the lack of AML-specific target antigens and clonal heterogeneity, leading to unwanted on-target off-leukemia toxicity risk relapse from minor clones. We hypothesize that combinatorial targeting AML cells can enhance therapeutic efficacy without increasing toxicity. To identify antigen combinations specific for leukemic stem cells, we generated a detailed protein expression profile based on flow cytometry primary (n =...
The bioenergetics and molecular determinants of the metabolic response to mitochondrial dysfunction are incompletely understood, in part due a lack appropriate isogenic cellular models primary defects. Here, we capitalize on recently developed cell model with defined levels m.8993T>G mutation heteroplasmy, mTUNE, investigate underpinnings dysfunction. We found that impaired utilization reduced nicotinamide adenine dinucleotide (NADH) by respiratory chain leads cytosolic reductive...
Abstract Digested dietary fats are taken up by enterocytes where they assembled into pre-chylomicrons in the endoplasmic reticulum followed transport to Golgi for maturation and subsequent secretion circulation 1 . The role of mitochondria lipid processing is unclear. Here we show that mitochondrial dysfunction inhibits chylomicron production lipids peripheral organs. Mice with specific ablation aspartyl-tRNA synthetase DARS2 (ref. 2 ), respiratory chain subunit SDHA 3 or assembly factor...
Current treatments for acute ischemic stroke aim to reinstate a normal perfusion in the territory but can also cause significant ischemia-reperfusion (IR) injury. Previous data experimental models of show that ischemia leads accumulation succinate, and, upon reperfusion, accumulated succinate is rapidly oxidized by dehydrogenase (SDH) drive superoxide production at mitochondrial complex I. Despite this process initiating IR injury and causing further tissue damage, potential targeting...
A key challenge for climate change mitigation on the consumer side is to break habits that excessively lead carbon emission. One of culturally most robust human routines heavy reliance Western societies conventional meat sources such as beef, pork, and poultry, which were recently accused causing particularly high costs. In this light, UN (FAO) has suggested increasing use insects an alternative source animal protein intended diets. Yet, have not reached mainstream cuisine. Currently, a...
Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression poorly understood. Here, we integrate multimodal analyses primary metastatic clonally-related clear cell renal cells (ccRCC) grown in physiological media to identify key stage-specific vulnerabilities. We show that a VHL loss-dependent branched-chain amino acid catabolism sustains de novo biosynthesis aspartate arginine enabling with...
Cancer is a multifaceted disease in which inherited genetic variants can be important drivers of tumorigenesis. The discovery that germline mutations metabolic genes predispose to familial forms cancer caused shift our understanding how metabolism contributes tumorigenesis, providing evidence alterations oncogenic. In this review, we focus on mitochondrial enzymes whose cancer, and fully appraise their involvement formation progression. Elucidating the molecular mechanisms orchestrate...
Immunotherapies, such as chimeric antigen receptor (CAR) modified T cells and antibody-drug conjugates (ADCs), have revolutionized the treatment of cancer, especially lymphoid malignancies. The application targeted immunotherapy to patients with acute myeloid leukemia (AML) has been limited in particular by lack a tumor-specific target antigen. Gemtuzumab ozogamicin (GO), an ADC targeting CD33, is only approved immunotherapeutic agent AML. In our study, we introduce CD33-directed...
Abstract Venetoclax/azacitidine combination therapy is effective in acute myeloid leukemia (AML) and tolerable for older, multimorbid patients. Despite promising response rates, many patients do not achieve sustained remission or are upfront refractory. Identification of resistance mechanisms additional therapeutic targets represent unmet clinical needs. By using a genome-wide CRISPR/Cas9 library screen targeting 18,053 protein- coding genes human AML cell line, various conferring to...
Immunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that might also influence BKV infection risk. In this case-control study RTx patients viremia within 4 years (BKV group) were compared a negative control group. The expressed as blood concentration normalized by daily dose (C/D ratio) was applied to assess rate. detected in 86 median time...
ABSTRACT The subfraction of extracellular vesicles, called exosomes, transfers biological molecular information not only between cells but also tissues and organs as nanolevel signals. Owing to their unique properties such that they contain several RNA species proteins implicated in kidney development, exosomes are putative candidates serve developmental programming units embryonic induction tissue interactions. We used the mammalian metanephric its nephron‐forming mesenchyme containing...
In atopic dermatitis (AD), lesional skin is frequently colonized by Staphylococcus aureus , which promotes clinical symptoms of the disease. The inflammatory milieu in characterized a Th2 response, including M2 macrophages, cannot eradicate S. . Therefore, repolarization macrophages toward M1 phenotype may foster control Our data show that deubiquitinating enzyme cylindromatosis ( CYLD ) strongly expressed AD patients and prevents clearance Mechanistically, impaired macrophage polarization...
Abstract Cells undergoing regulated necrosis systemically communicate with the immune system via release of protein and non-protein secretomes. Ferroptosis is a recently described iron-dependent type driven by massive lipid peroxidation. While membrane rupture occurs during ferroptosis, comprehensive appraisal ferroptotic secretomes their potential biological activity has been lacking. Here, we apply multi-omics approach to provide an atlas ferroptosis-induced reveal novel function in...
Purpose Entomophagy (i.e. human insect consumption) is seen as one promising route to substantially reduce food-related carbon footprints insects can be produced at a fraction of the emitted by traditional Western meat production (e.g. beef, pork, poultry). In this light, purpose paper address how prices may affect preferences for food. Design/methodology/approach Drawing on consumer research “positive” functions widely held belief that price and quality are positively correlated), authors...
Abstract From the catalytic breakdown of nutrients to signaling, interactions between metabolites and proteins play an essential role in cellular function. An important case is cell–cell communication, where metabolites, secreted into microenvironment, initiate signaling cascades by binding intra- or extracellular receptors neighboring cells. Protein–protein communication are routinely predicted from transcriptomic data. However, inferring metabolite-mediated intercellular remains...
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a syndrome caused by inactivating germline mutations in fumarate hydratase (FH) subsequent accumulation of fumarate. Fumarate leads to profound epigenetic changes the activation an anti-oxidant response via nuclear translocation transcription factor NRF2. The extent which chromatin remodeling shapes this currently unknown. Here, we explored effects FH loss on landscape identify networks involved remodeled FH-deficient cells. We FOXA2...
The inflammation regulating transcription factor NFκB and the tumor-suppressing p53 can act as functional antagonists. Chronic (NFκB activity) may contribute to development of cancer through inhibition function, while, conversely, activity dampen inflammation. Here we report that E3 ubiquitin ligase MDM2, whose gene is transcriptionally activated by both p53, bind inhibit p65RelA subunit NFκB. interaction mediated N-terminal acidic/zinc finger domains MDM2 on one hand Rel homology domain...
The objective of our study was to investigate the tandem irritation potential two organic solvents with concurrent exposure hydrophilic detergent irritant sodium lauryl sulphate (SLS). A repeated test performed undiluted solvents, cumene (C) and octane (O), either alternating application SLS 0.5% or twice daily each alone in 27 volunteers on skin back. cumulative induced over 4 days quantified using visual scoring non-invasive bioengineering measurements (skin colour reflectance, hydration...
Fumarate hydratase (FH) is a mitochondrial enzyme that catalyzes the reversible hydration of fumarate to malate in tricarboxylic acid (TCA) cycle. Germline mutations FH lead hereditary leiomyomatosis and renal cell carcinoma (HLRCC), cancer syndrome characterized by highly aggressive form cancer. Although HLRCC tumors metastasize rapidly, FH-deficient mice develop premalignant cysts kidneys, rather than carcinomas. How Fh1 -deficient cells overcome these tumor-suppressive events during...