A5050661206- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Sirtuins and Resveratrol in Medicine
- Muscle metabolism and nutrition
- Hedgehog Signaling Pathway Studies
- RNA modifications and cancer
- Regulation of Appetite and Obesity
- Peptidase Inhibition and Analysis
- Protein Tyrosine Phosphatases
- Genomics and Chromatin Dynamics
- Fatty Acid Research and Health
- Liver Disease Diagnosis and Treatment
- Signaling Pathways in Disease
- Biochemical and Molecular Research
- MicroRNA in disease regulation
- Protein Degradation and Inhibitors
- Neonatal Respiratory Health Research
- Glioma Diagnosis and Treatment
- Biochemical effects in animals
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- Tea Polyphenols and Effects
- Circadian rhythm and melatonin
- Epigenetics and DNA Methylation
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
Medical Research Council
2022
Cancer Research UK
2022
University of Oxford
2022
CRUK/MRC Oxford Institute for Radiation Oncology
2022
University of Geneva
2015-2020
Available treatment for obesity and type 2 diabetes mellitus (T2DM) is suboptimal. Thus, identifying novel molecular target(s) exerting protective effects against these metabolic imbalances of enormous medical significance. Sirt6 loss- gain-of-function studies have generated confounding data regarding the role this sirtuin on energy glucose homeostasis, leaving unclear whether activation or inhibition SIRT6 may be beneficial and/or T2DM.To address issues, we developed studied a mouse model...
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer are reduced by overexpression the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive bear mutations activate phosphatidylinositol-3-kinase (PI3K) signaling, and SIRT6 reduces growth, progression, grade breast in a mouse model with PI3K activation. Tumor metabolomic transcriptomic analyses reveal dampens signaling characteristics causes metabolic rearrangements this model....
Abstract Obesity-induced inflammation engenders insulin resistance and type 2 diabetes mellitus (T2DM) but the inflammatory effectors linking obesity to are incompletely understood. Here, we show that hepatic expression of Protein Tyrosine Phosphatase Receptor Gamma (PTPR-γ) is stimulated by in obese/T2DM mice positively correlates with indices humans. NF-κB binds promoter Ptprg required for inflammation-induced PTPR-γ expression. loss-of-function lowers glycemia insulinemia enhancing...
Cancer therapy is limited, in part, by lack of specificity. Thus, identifying molecules that are selectively expressed by, and relevant for, cancer cells paramount medical importance. Here, we show peptidyl-prolyl-cis-trans-isomerase (PPIase) FK506-binding protein 10 (FKBP10)-positive present lesions but absent the healthy parenchyma human lung. FKBP10 expression negatively correlates with survival lung patients, its downregulation causes a dramatic diminution tumor burden mice....
Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary molecular mechanisms able to improve is paramount medical importance because such can be leveraged as a therapy for obesity related disorders. Here, we show that designer protein-deprived diet enriched free essential amino acids 1) promote the brown fat thermogenic program fatty acid oxidation, 2) stimulate uncoupling protein 1 (UCP1)-independent respiration subcutaneous white...
Abstract Medulloblastoma is the most common malignant brain tumour in children. Genomic studies have identified distinct disease subgroups: wnt/wingless (WNT), sonic hedgehog (SHH), and non-WNT/non-SHH, comprising group 3 4. Alterations WNT SHH signalling form pathogenetic basis for their subgroups, whereas those non-WNT/non-SHH tumours remain largely elusive. Recent analyses revealed recurrent in-frame insertions E3 ubiquitin ligase adaptor Kelch Repeat BTB Domain Containing 4 (KBTBD4)...
Loss of synchrony between geophysical time and insulin action predisposes to metabolic diseases. Yet the brain peripheral pathways linking proper effect diurnal changes in light-dark feeding-fasting inputs are poorly understood. Here, we show that sensitivity several metabolically relevant tissues fluctuates during 24 h period. For example, mice, skeletal muscle, liver, adipose tissue is lowest light Mechanistically, by performing loss- gain-of-light-action food-restriction experiments,...
Abstract Tens of millions suffer from insulin deficiency (ID); a defect leading to severe metabolic imbalance and death. The only means for management ID is therapy; yet, this approach sub-optimal causes life-threatening hypoglycemia. Hence, represents great medical societal challenge. Here we report that S100A9, also known as Calgranulin B or Myeloid-Related Protein 14 (MRP14), leptin-induced circulating cue exerting beneficial anti-diabetic action. In murine models ID, enhanced expression...
Abstract Genomic studies in medulloblastoma have identified distinct disease subgroups: wnt/wingless (WNT), sonic hedgehog (SHH), and non-WNT/non-SHH, comprising group 3 4. Alterations WNT SHH signalling form the pathogenetic basis for their subgroups, whereas those non-WNT/non-SHH tumours remain largely elusive. Recent analyses revealed recurrent in-frame insertions E3 ubiquitin ligase adaptor Kelch Repeat BTB Domain Containing 4 (KBTBD4) cases of medulloblastoma. Critically, with KBTBD4...
ABSTRACT Introduction Cancer therapy is limited by lack of specificity. Thus, identifying molecules that are relevant for tumorigenesis and selectively expressed cancer cells paramount medical importance. Here, following computational immunohistological analyses, we found in both mouse human FKBP10 an oncofetal protein during adulthood lung cells. Our results from vitro vivo functional assays demonstrated downregulation hinders growth tumours owing to decreased cell proliferation. By...
Reduced activity of thermogenic adipocytes leads to increased adiposity and defects in glucose metabolism. Thus, exploring dietary molecular mechanisms able stimulate these is paramount medical importance, as such can be leveraged a therapy for obesity and/or type 2 diabetes. Here, we show that designer diet enriched soluble essential amino acids i) promote brown fat thermogenesis, ii) uncoupling protein 1 (UCP1)-independent respiration subcutaneous white adipose tissue, iii) prevent reverse...
Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary molecular mechanisms able to improve is paramount medical importance, as such can be leveraged a therapy for obesity related disorders. Here, <a>we show that designer protein-deprived diet enriched free essential amino acids i) promote the brown fat thermogenic program fatty acid oxidation, ii) stimulate uncoupling protein 1 (UCP1)-independent respiration subcutaneous white...
Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary molecular mechanisms able to improve is paramount medical importance, as such can be leveraged a therapy for obesity related disorders. Here, <a>we show that designer protein-deprived diet enriched free essential amino acids i) promote the brown fat thermogenic program fatty acid oxidation, ii) stimulate uncoupling protein 1 (UCP1)-independent respiration subcutaneous white...