David E James



  1. Yang G, Humphrey S, Murashige D, Francis D, Wang Q, Cooke K, et al. RagC phosphorylation autoregulates mTOR complex 1. EMBO J. 2018;: pubmed publisher
    ..Finally, we identify mTORC1 as the upstream kinase of RagC on S21. Our data highlight the importance of RagC phosphorylation in its function and identify a previously unappreciated auto-regulatory mechanism of mTORC1 activity. ..
  2. Fazakerley D, Krycer J, Kearney A, Hocking S, James D. Muscle and adipose tissue insulin resistance: malady without mechanism?. J Lipid Res. 2018;: pubmed publisher
    ..This review highlights key points in this pathway that require further research effort. ..
  3. Tan S, Fisher Wellman K, Fazakerley D, Ng Y, Pant H, Li J, et al. Selective insulin resistance in adipocytes. J Biol Chem. 2015;290:11337-48 pubmed publisher
    ..We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin. ..
  4. Parker B, Yang G, Humphrey S, Chaudhuri R, Ma X, Peterman S, et al. Targeted phosphoproteomics of insulin signaling using data-independent acquisition mass spectrometry. Sci Signal. 2015;8:rs6 pubmed publisher
  5. Phua Y, Nguyen A, Roden D, Elsworth B, Deng N, Nikolic I, et al. MicroRNA profiling of the pubertal mouse mammary gland identifies miR-184 as a candidate breast tumour suppressor gene. Breast Cancer Res. 2015;17:83 pubmed publisher
    ..These studies elucidate a new layer of regulation in the PI3K/AKT/mTOR pathway with relevance to mammary development and tumour progression and identify miR-184 as a putative breast tumour suppressor. ..
  6. Su Z, Deshpande V, James D, Stöckli J. Tankyrase modulates insulin sensitivity in skeletal muscle cells by regulating the stability of GLUT4 vesicle proteins. J Biol Chem. 2018;293:8578-8587 pubmed publisher
    ..These studies reveal an important role for tankyrase in maintaining the stability of key GLUT4 regulatory proteins that in turn plays a role in regulating cellular insulin sensitivity. ..
  7. Fazakerley D, Minard A, Krycer J, Thomas K, Stöckli J, Harney D, et al. Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation. J Biol Chem. 2018;293:7315-7328 pubmed publisher
  8. Burchfield J, Kebede M, Meoli C, Stöckli J, Whitworth P, Wright A, et al. High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice. J Biol Chem. 2018;293:5731-5745 pubmed publisher
    ..Overall, the excessive calorie intake was accompanied by deteriorating function of numerous physiological systems. ..
  9. Parker B, Thaysen Andersen M, Fazakerley D, Holliday M, Packer N, James D. Terminal Galactosylation and Sialylation Switching on Membrane Glycoproteins upon TNF-Alpha-Induced Insulin Resistance in Adipocytes. Mol Cell Proteomics. 2016;15:141-53 pubmed publisher
    ..This revealed the modulation of N-glycosylation on specific proteins in IR, including those previously associated with insulin-stimulated GLUT4 trafficking to the plasma membrane. ..

More Information


  1. Humphrey S, James D, Mann M. Protein Phosphorylation: A Major Switch Mechanism for Metabolic Regulation. Trends Endocrinol Metab. 2015;26:676-87 pubmed publisher
  2. 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. ..
  3. 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. ..
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. 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. ..
  9. Stöckli 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. ..
  10. 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
  11. 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. ..
  12. 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. ..
  13. Chaudhuri R, Sadrieh A, Hoffman N, Parker B, Humphrey S, Stöckli 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. ..
  14. 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 PPARγ action in the adipocyte. Further studies are required to establish the exact role of TUSC5 in adipocytes. ..
  15. 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. ..
  16. 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. ..