A5070441623- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Cancer-related Molecular Pathways
- Genetics, Aging, and Longevity in Model Organisms
- Single-cell and spatial transcriptomics
- FOXO transcription factor regulation
- interferon and immune responses
- Pluripotent Stem Cells Research
- Hematopoietic Stem Cell Transplantation
- Cancer Mechanisms and Therapy
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- Metabolism, Diabetes, and Cancer
- Microtubule and mitosis dynamics
- Cancer Research and Treatments
- Inflammasome and immune disorders
- Birth, Development, and Health
- Neuroblastoma Research and Treatments
- Erythrocyte Function and Pathophysiology
- Cancer therapeutics and mechanisms
- Invertebrate Immune Response Mechanisms
- Clinical Nutrition and Gastroenterology
Max Planck Institute for Biology of Ageing
2020-2024
University Hospital Cologne
2019-2023
University of Cologne
2019-2023
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2019-2021
Heinrich Heine University Düsseldorf
2019
Düsseldorf University Hospital
2019
Small cell size preserves the function of hematopoietic stem cells (HSCs); HSC enlargement during aging causes their dysfunction.
Late-life-initiated dietary interventions show limited efficacy in extending longevity or mitigating frailty, yet the underlying causes remain unclear. Here we studied age-related fasting response of short-lived killifish Nothobranchius furzeri. Transcriptomic analysis uncovered existence a fasting-like transcriptional program adipose tissue old fish that overrides feeding response, setting persistent metabolic quiescence. The fasting-refeeding cycle triggers an inverse oscillatory...
The advent of molecularly targeted therapeutic agents has opened a new era in cancer therapy. However, many tumors rely on nondruggable cancer-driving lesions. In addition, long-lasting clinical benefits from single-agent therapies rarely occur, as most the acquire resistance over time. identification combination regimens interfering with signaling through oncogenically rewired pathways provides promising approach to enhance efficacy single-agent-targeted treatments. Moreover, drug might...
Abstract Objective We describe a family with novel mutation in the TNF Receptor Superfamily Member 1A (TNFRSF1A) gene causing receptor–associated periodic syndrome (TRAPS) renal AA amyloidosis. Methods Case series of affected members. further investigated plasma metabolome these patients comparison healthy controls using mass spectrometry. Results In all symptomatic members, we detected previously undescribed variant c.332A>G (p.Q111R) TNFRSF1A gene. Canakinumab proved an effective...
Abstract Stem cells are remarkably small in size. Whether size is important for stem cell function unknown. We find that murine hematopoietic (HSCs) enlarge under conditions known to decrease function. This decreased fitness of large HSCs due reduced proliferative potential. Preventing HSC enlargement by inhibiting macromolecule biosynthesis or reducing shortening G 1 averts the loss potential causing exhaustion. Finally, we show a fraction and human during aging. this age-dependent improves...
Abstract The cGAS/STING pathway is a central innate immune signaling whose chronic activation has been implicated in numerous age-related pathologies, yet its impact on life span itself unknown. Here we engineered knockouts of this the killifish Nothobranchius furzeri , and assessed physiology aging. In vitro loss cGAS or STING mitigated DNA damage-induced senescence cultured fibroblasts. vivo knockout unexpectedly led to low-grade inflammation. It also attenuated changes gene expression...
Abstract Caloric Restriction (CR) extends lifespan and augments cellular stress-resistance from yeast to primates, making CR an attractive strategy for organ protection in the clinic. Translation of patients is complex, due problems regarding adherence, feasibility safety concerns frail patients. Novel tailored dietary regimens, which modulate composition macro- micronutrients rather than reducing calorie intake promise similar protective effects increased translatability. However, a direct...
<p>Additional information on data analysis and experimental procedures are included in the Supplementary Methods.</p>
<p>Table S6 contains all p-values related to Fig. 4C.</p>
<p>Table S3 contains normalized cell viability values of 4x4 combination experiments (original data Fig. S2).</p>
<p>Table S1 complements the Material and Methods part listing cell lines growing conditions, primer sequences, antibodies, compounds their concentrations.</p>
<p>Table S4 contains all apoptotic effects of single agent inhibitors and their combinations (original data Fig 1C Fig. S3).</p>
<p>Table S5 contains data of the GSEA analysis.</p>
<p>Table S2 contains normalized cell viability values of single agent dose-response curves 18 compounds employed in the screen (original data Fig. S1).</p>
<p>Figure S1 shows single agent dose-response curves of 18 compounds employed in the screen. Figure S2 synergy scores 23 compound combinations. S3 apoptotic effects inhibitors and their combinations on a panel 24 cell lines. S4 for 6x6 concentration combined CHK1/GLUT1 or ATR/GLUT1 inhibition as well tumor volume fold changes A549- HCC44-derived xenografts treated with CHK1-inhibitor, GLUT1-inhibitor combination both. S5 CHK1/HER2 HER2-inhibitor S6 that sensitive lines are enriched...
<p>Figure S1 shows single agent dose-response curves of 18 compounds employed in the screen. Figure S2 synergy scores 23 compound combinations. S3 apoptotic effects inhibitors and their combinations on a panel 24 cell lines. S4 for 6x6 concentration combined CHK1/GLUT1 or ATR/GLUT1 inhibition as well tumor volume fold changes A549- HCC44-derived xenografts treated with CHK1-inhibitor, GLUT1-inhibitor combination both. S5 CHK1/HER2 HER2-inhibitor S6 that sensitive lines are enriched...
<p>Table S4 contains all apoptotic effects of single agent inhibitors and their combinations (original data Fig 1C Fig. S3).</p>
<p>Table S3 contains normalized cell viability values of 4x4 combination experiments (original data Fig. S2).</p>
<p>Table S1 complements the Material and Methods part listing cell lines growing conditions, primer sequences, antibodies, compounds their concentrations.</p>
<p>Additional information on data analysis and experimental procedures are included in the Supplementary Methods.</p>
<p>Table S6 contains all p-values related to Fig. 4C.</p>
<p>Table S5 contains data of the GSEA analysis.</p>
<p>Table S2 contains normalized cell viability values of single agent dose-response curves 18 compounds employed in the screen (original data Fig. S1).</p>