David E James
- Chaudhuri R, Krycer J, Fazakerley D, Fisher Wellman K, Su Z, Hoehn K, et al. The transcriptional response to oxidative stress is part of, but not sufficient for, insulin resistance in adipocytes. Sci Rep. 2018;8:1774 pubmed publisher..This suggests that the primary site by which oxidative stress impairs insulin action occurs post-transcriptionally, warranting a multi-level 'trans-omic' approach when studying time-resolved responses to cellular perturbations. ..
- Trefely S, Khoo P, Krycer J, Chaudhuri R, Fazakerley D, Parker B, et al. Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/Insulin-like Growth Factor (IGF)-1 Signaling Pathway. J Biol Chem. 2015;290:25834-46 pubmed publisher..Our findings have important implications for diseases such as type 2 diabetes and cancer that are characterized by marked disruption of both metabolism and growth factor signaling. ..
- Hoffman N, Parker B, Chaudhuri R, Fisher Wellman K, Kleinert M, Humphrey S, et al. Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates. Cell Metab. 2015;22:922-35 pubmed publisher..These data expose the unexplored complexity of acute exercise signaling and provide insights into the role of AMPK in mitochondrial biochemistry. ..
- Wu L, Meoli C, Mangiafico S, Fazakerley D, Cogger V, Mohamad M, et al. Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction. Diabetes. 2014;63:2656-67 pubmed publisher..These findings show an important and unexpected role for VEGF in liver insulin resistance, opening up a potentially novel therapeutic avenue for obesity-related metabolic disease. ..
- Minard A, Tan S, Yang P, Fazakerley D, Domanova W, Parker B, et al. mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes. Cell Rep. 2016;17:29-36 pubmed publisher..This study provides a global view of FGF21 signaling and suggests that mTORC1 may act to facilitate FGF21-mediated health benefits in vivo. ..
- Krycer J, Fisher Wellman K, Fazakerley D, Muoio D, James D. Bicarbonate alters cellular responses in respiration assays. Biochem Biophys Res Commun. 2017;489:399-403 pubmed publisher..Permeabilised cell experiments suggest that bicarbonate increases substrate availability, likely by acting as a cofactor for carboxylase enzymes. This emphasises the importance of buffer choice in experimental biology. ..
- Stöckli J, Fisher Wellman K, Chaudhuri R, Zeng X, Fazakerley D, Meoli C, et al. Metabolomic analysis of insulin resistance across different mouse strains and diets. J Biol Chem. 2017;292:19135-19145 pubmed publisher..These data indicate the power of simultaneous analysis of individual, genetic, and environmental variance in mice for identifying novel factors that accurately predict metabolic phenotypes like whole-body insulin sensitivity. ..
- StÃ¶ckli J, Meoli C, Hoffman N, Fazakerley D, Pant H, Cleasby M, et al. The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle. Diabetes. 2015;64:1914-22 pubmed publisher..These findings indicate that the RabGAP TBC1D1 plays a key role in regulating GLUT4 protein levels and in exercise-mediated glucose uptake in nonoxidative muscle fibers. ..
- Chaudhuri R, Sadrieh A, Hoffman N, Parker B, Humphrey S, StÃ¶ckli J, et al. PhosphOrtholog: a web-based tool for cross-species mapping of orthologous protein post-translational modifications. BMC Genomics. 2015;16:617 pubmed publisher..Moreover, PhosphOrtholog is generic being applicable to other PTM datasets such as acetylation, ubiquitination and methylation. ..
- Minard A, Wong M, Chaudhuri R, Tan S, Humphrey S, Parker B, et al. Hyperactivation of the Insulin Signaling Pathway Improves Intracellular Proteostasis by Coordinately Up-regulating the Proteostatic Machinery in Adipocytes. J Biol Chem. 2016;291:25629-25640 pubmed
- Parker B, Burchfield J, Clayton D, Geddes T, Payne R, Kiens B, et al. Multiplexed Temporal Quantification of the Exercise-regulated Plasma Peptidome. Mol Cell Proteomics. 2017;16:2055-2068 pubmed publisher..This will likely be a key method for pinpointing exercise regulated factors that generate health benefits. ..
- Krycer J, Yugi K, Hirayama A, Fazakerley D, Quek L, Scalzo R, et al. Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism. Cell Rep. 2017;21:3536-3547 pubmed publisher..This complements the supply-driven regulation of anabolism by substrate accumulation and highlights an additional role for insulin action in adipocyte glucose metabolism. ..
- Fazakerley D, Naghiloo S, Chaudhuri R, Koumanov F, Burchfield J, Thomas K, et al. Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumor Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes. J Biol Chem. 2015;290:23528-42 pubmed publisher..These findings functionally link TUSC5 to GLUT4 trafficking, insulin action, insulin resistance, and PPARÎ³ action in the adipocyte. Further studies are required to establish the exact role of TUSC5 in adipocytes. ..
- Yang G, Murashige D, Humphrey S, James D. A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation. Cell Rep. 2015;12:937-43 pubmed publisher..Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt. ..
- Ma X, Yang P, Kaplan W, Lee B, Wu L, Yang J, et al. ISL1 regulates peroxisome proliferator-activated receptor ? activation and early adipogenesis via bone morphogenetic protein 4-dependent and -independent mechanisms. Mol Cell Biol. 2014;34:3607-17 pubmed publisher..Our time course gene expression survey sets the stage for further studies to explore other early and immediate regulators. ..