Dr Daniel Fazakerley

Group leader - Mechanisms of Insulin Resistance
Research Fellow
School of Life and Environmental Sciences

Member of the Charles Perkins Centre

D17 - Charles Perkins Centre
The University of Sydney

Telephone +61 2 8627 1978

Biographical details

Dr Daniel Fazakerley is a post-doctoral fellow in the School of Life and Environmental Sciences based at the Charles Perkins Centre. He investigates how cells and tissues respond to insulin and how these responses become defective in metabolic disease. His overall goal is to find new ways to improve or restore insulin action. He currently leads the Mechanisms of Insulin Resistance group as part of Professor David James' lab.

Dr Fazakerley studied for his PhD with Professor Geoff Holman at the University at Bath from 2006 to 2010. During this time he investigated the intracellular trafficking of the glucose transporter, GLUT4, in skeletal muscle. Following award of his PhD in 2010, Dr Fazakerley joined Professor James’ group, then at the Garvan Institute in Sydney, on a Sir Henry Wellcome Fellowship from the Wellcome Trust. He moved to his current position at the CPC in 2014.

Research interests

Dr Fazakerley investigates how normal cellular responses to insulin are perturbed in pre-diabetes or insulin resistance. While we have known for a long time that impaired insulin-stimulated glucose transport in muscle and fat is a major cause of insulin resistance there is no consensus on the cellular stresses that cause insulin resistance in these tissues or the molecular basis for impaired insulin responses. Using proteomic techniques he has revealed a range of cellular pathways that are perturbed in insulin resistance and that appear to impinge on insulin action. His major focus is understanding how these proteins and pathways regulate insulin action and whether they can be targeted to overcome insulin resistance.

Current research students

Project title Research student
The role of Trafficking regulator of GLUT4 1 (TRARG1) in GLUT4 trafficking Xiaowen DUAN
Pancreatic Islet Cell Atlas Sheyda NAGHILOO

International links

United Kingdom

(MRC Mitochondrial Biology Unit University of Cambridge) Dr Mike Murphy

United Kingdom

(University of Bath) Dr Francoise Koumanov

Selected grants

2018

  • Redefining insulin resistance as a metabolic defect beyond glucose transport; Krycer J, James D, Fazakerley D, Healy M, Quek L; Diabetes Australia/Diabetes Research Grant Program.

2017

  • GLUT4 trafficking and insulin resistance; Burchfield J, Fazakerley D; Diabetes Australia/Research Grant.

2013

  • Investigating FABP4 as an insulinotropic adipokine; Fazakerley D; National Health and Medical Research Council (NHMRC)/Project Grants.

Selected publications

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Book Chapters

  • Norris, D., Geddes, T., James, D., Fazakerley, D., Burchfield, J. (2018). Glucose transport: Methods for interrogating GLUT4 trafficking in adipocytes. Methods in Molecular Biology, (pp. 193-215). [More Information]

Journals

  • Krycer, J., Diskin, C., Healy, M., Zeng, X., Fazakerley, D., James, D. (2018). A gas trapping method for high-throughput metabolic experiments. BioTechniques, 64(1), 27-29. [More Information]
  • Burchfield, J., Kebede, M., Meoli, C., Stoeckli, J., Whitworth, P., Wright, A., Hoffman, N., Minard, A., Ma, X., Krycer, J., Healy, M., Yau, B., Thomas, K., Cooney, G., James, D., Fazakerley, D., et al (2018). High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice. Journal of Biological Chemistry, 293(15), 5731-5745. [More Information]
  • Duan, X., Krycer, J., Cooke, K., Yang, G., James, D., Fazakerley, D. (2018). Membrane Topology of Trafficking Regulator of GLUT4 1 (TRARG1). Biochemistry, 57(26), 3606-3615. [More Information]
  • Fazakerley, D., Chaudhuri, R., Yang, P., Maghazal, G., Thomas, K., Krycer, J., Humphrey, S., Parker, B., Fisher-Wellman, K., Meoli, C., Hoffman, N., Diskin, C., Burchfield, J., Yang, J., James, D., et al (2018). Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. eLife, 7, 1-38. [More Information]
  • Fazakerley, D., Minard, A., Krycer, J., Thomas, K., Stoeckli, J., Harney, D., Burchfield, J., Maghzal, G., Caldwell, S., Hartley, R., James, D., et al (2018). Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation. Journal of Biological Chemistry, 293(19), 7315-7328. [More Information]
  • Chaudhuri, R., Krycer, J., Fazakerley, D., Fisher-Wellman, K., Su, Z., Hoehn, K., Yang, Y., Kuncic, Z., Vafaee, F., James, D. (2018). The transcriptional response to oxidative stress is part of, but not sufcient for, insulin resistance in adipocytes. Scientific Reports, 8(1), 1774 - 1-1774 - 15. [More Information]
  • Chaudhuri, R., Krycer, J., Fazakerley, D., Fisher-Wellman, K., Su, Z., Hoehn, K., Yang, J., Kuncic, Z., Vafaee, F., James, D. (2018). The transcriptional response to oxidative stress is part of, but not sufficient for, insulin resistance in adipocytes. Scientific Reports, 8(1), 1-15. [More Information]
  • Balaban, S., Shearer, R., Lee, L., van Geldermalsen, M., Schreuder, M., Shtein, H., Cairns, R., Thomas, K., Fazakerley, D., Grewal, T., Holst, J., Hoy, A., et al (2017). Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer and Metabolism, 5(1). [More Information]
  • Norris, D., Yang, P., Krycer, J., Fazakerley, D., James, D., Burchfield, J. (2017). An improved Akt reporter reveals intra- and inter-cellular heterogeneity and oscillations in signal transduction. Journal of Cell Science, 130, 2757-2766. [More Information]
  • Krycer, J., Fisher-Wellman, K., Fazakerley, D., Muoio, D., James, D. (2017). Bicarbonate alters cellular responses in respiration assays. Biochemical and Biophysical Research Communications, 489, 399-403. [More Information]
  • Krycer, J., Yugi, K., Hirayama, A., Fazakerley, D., Quek, L., Scalzo, R., Ohno, S., Hodson, M., Ikeda, S., Shoji, F., Domanova, W., Parker, B., Healy, M., Humphrey, S., Cooney, G., James, D., et al (2017). Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism. Cell Reports, 21(12), 3536-3547. [More Information]
  • Stoeckli, J., Fisher-Wellman, K., Chaudhuri, R., Zeng, X., Fazakerley, D., Meoli, C., Thomas, K., Hoffman, N., Mangiafico, S., Xirouchaki, C., Cooney, G., James, D., et al (2017). Metabolomic analysis of insulin resistance across different mouse strains and diets. Journal of Biological Chemistry, 292(47), 19135-19145. [More Information]
  • Krycer, J., Fazakerley, D., Cater, R., Thomas, K., Naghiloo, S., Burchfield, J., Humphrey, S., Vandenberg, R., Ryan, R., James, D. (2017). The amino acid transporter SLC1A3 is plasma membrane-localised in adipocytes and its activity is insensitive to insulin. FEBS Letters, 591(2), 322-330. [More Information]
  • Minard, A., Tan, S., Yang, P., Fazakerley, D., Domanova, W., Parker, B., Humphrey, S., Jothi, R., Stoeckli, J., James, D. (2016). mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes. Cell Reports, 17(1), 29-36. [More Information]
  • Kleinert, M., Parker, B., Chaudhuri, R., Fazakerley, D., Serup, A., Thomas, K., Krycer, J., Sylow Hansen, L., Fritzen, A., Hoffman, N., James, D., et al (2016). mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3. Molecular Metabolism, 5(8), 646-655. [More Information]
  • Parker, B., Thaysen-Andersen, M., Fazakerley, D., Holliday, M., Packer, N., James, D. (2016). Terminal Galactosylation and Sialylation Switching on Membrane Glycoproteins upon TNF-Alpha-Induced Insulin Resistance in Adipocytes. Molecular and Cellular Proteomics, 15(1), 141-153. [More Information]
  • Domanova, W., Krycer, J., Chaudhuri, R., Yang, P., Vafaee, F., Fazakerley, D., Humphrey, S., James, D., Kuncic, Z. (2016). Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies. PloS One, 11(6), 1-14. [More Information]
  • Wu, L., Fazakerley, D., Cantley, J. (2015). Circulating AFABP promotes insulin secretion. Obesity, 23(8), 1525-2-s2.0-84937519995. [More Information]
  • Chaudhuri, R., Khoo, P., Tonks, K., Junutula, J., Kolumam, G., Modrusan, Z., Samocha-Bonet, D., Meoli, C., Hocking, S., Fazakerley, D., Stockli, J., Yang, J., James, D., et al (2015). Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity. Npj Systems Biology And Applications, 1, 1-10. [More Information]
  • Hoffman, N., Parker, B., Chaudhuri, R., Fisher-Wellman, K., Kleinert, M., Humphrey, S., Yang, P., Holliday, M., Trefely, S., Fazakerley, D., Stoeckli, J., Burchfield, J., James, D., et al (2015). Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates. Cell Metabolism, 22(5), 922-935. [More Information]
  • Koumanov, F., Pereira, V., Richardson, J., Sargent, S., Fazakerley, D., Holman, G. (2015). Insulin regulates Rab3-Noc2 complex dissociation to promote GLUT4 translocation in rat adipocytes. Diabetologia, 58(8), 1877-1886. [More Information]
  • Trefely, S., Khoo, P., Krycer, J., Chaudhuri, R., Fazakerley, D., Parker, B., Sultani, G., Lee, J., Stephan, J., Torres, E., James, D., Stoeckli, J., et al (2015). Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/IGF-1 Signalling Pathway. Journal of Biological Chemistry, 290(43), 25834-25846. [More Information]
  • Fazakerley, D., Naghiloo, S., Chaudhuri, R., Koumanov, F., Burchfield, J., Thomas, K., Krycer, J., Prior, M., Parker, B., Murrow, B., Stoeckli, J., Meoli, C., James, D., et al (2015). Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumour Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes. Journal of Biological Chemistry, 290(39), 23528-23542. [More Information]
  • Tan, S., Fisher_Wellman, K., Fazakerley, D., Ng, Y., Pant, H., Li, J., Meoli, C., Coster, A., Stoeckli, J., James, D. (2015). Selective insulin resistance in adipocytes. Journal of Biological Chemistry, 290(18), 11337-11348. [More Information]
  • Stoeckli, J., Meoli, C., Hoffman, N., Fazakerley, D., Pant, H., Cleasby, M., Ma, X., Kleinert, M., Brandon, A., Lopez, J., James, D., et al (2015). The RabGAP TBC1D1 Plays a Central Role in Exercise-Regulated Glucose Metabolism in Skeletal Muscle. Diabetes, 64(6), 1914-1922. [More Information]
  • Kleinert, M., Sylow Hansen, L., Fazakerley, D., Krycer, J., Thomas, K., Oxbøll, A., Jordy, A., Jensen, T., Yang, G., Schjerling, P., James, D., et al (2014). Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo. Molecular Metabolism, 3(6), 630-641. [More Information]

2018

  • Krycer, J., Diskin, C., Healy, M., Zeng, X., Fazakerley, D., James, D. (2018). A gas trapping method for high-throughput metabolic experiments. BioTechniques, 64(1), 27-29. [More Information]
  • Norris, D., Geddes, T., James, D., Fazakerley, D., Burchfield, J. (2018). Glucose transport: Methods for interrogating GLUT4 trafficking in adipocytes. Methods in Molecular Biology, (pp. 193-215). [More Information]
  • Burchfield, J., Kebede, M., Meoli, C., Stoeckli, J., Whitworth, P., Wright, A., Hoffman, N., Minard, A., Ma, X., Krycer, J., Healy, M., Yau, B., Thomas, K., Cooney, G., James, D., Fazakerley, D., et al (2018). High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice. Journal of Biological Chemistry, 293(15), 5731-5745. [More Information]
  • Duan, X., Krycer, J., Cooke, K., Yang, G., James, D., Fazakerley, D. (2018). Membrane Topology of Trafficking Regulator of GLUT4 1 (TRARG1). Biochemistry, 57(26), 3606-3615. [More Information]
  • Fazakerley, D., Chaudhuri, R., Yang, P., Maghazal, G., Thomas, K., Krycer, J., Humphrey, S., Parker, B., Fisher-Wellman, K., Meoli, C., Hoffman, N., Diskin, C., Burchfield, J., Yang, J., James, D., et al (2018). Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. eLife, 7, 1-38. [More Information]
  • Fazakerley, D., Minard, A., Krycer, J., Thomas, K., Stoeckli, J., Harney, D., Burchfield, J., Maghzal, G., Caldwell, S., Hartley, R., James, D., et al (2018). Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation. Journal of Biological Chemistry, 293(19), 7315-7328. [More Information]
  • Chaudhuri, R., Krycer, J., Fazakerley, D., Fisher-Wellman, K., Su, Z., Hoehn, K., Yang, Y., Kuncic, Z., Vafaee, F., James, D. (2018). The transcriptional response to oxidative stress is part of, but not sufcient for, insulin resistance in adipocytes. Scientific Reports, 8(1), 1774 - 1-1774 - 15. [More Information]
  • Chaudhuri, R., Krycer, J., Fazakerley, D., Fisher-Wellman, K., Su, Z., Hoehn, K., Yang, J., Kuncic, Z., Vafaee, F., James, D. (2018). The transcriptional response to oxidative stress is part of, but not sufficient for, insulin resistance in adipocytes. Scientific Reports, 8(1), 1-15. [More Information]

2017

  • Balaban, S., Shearer, R., Lee, L., van Geldermalsen, M., Schreuder, M., Shtein, H., Cairns, R., Thomas, K., Fazakerley, D., Grewal, T., Holst, J., Hoy, A., et al (2017). Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer and Metabolism, 5(1). [More Information]
  • Norris, D., Yang, P., Krycer, J., Fazakerley, D., James, D., Burchfield, J. (2017). An improved Akt reporter reveals intra- and inter-cellular heterogeneity and oscillations in signal transduction. Journal of Cell Science, 130, 2757-2766. [More Information]
  • Krycer, J., Fisher-Wellman, K., Fazakerley, D., Muoio, D., James, D. (2017). Bicarbonate alters cellular responses in respiration assays. Biochemical and Biophysical Research Communications, 489, 399-403. [More Information]
  • Krycer, J., Yugi, K., Hirayama, A., Fazakerley, D., Quek, L., Scalzo, R., Ohno, S., Hodson, M., Ikeda, S., Shoji, F., Domanova, W., Parker, B., Healy, M., Humphrey, S., Cooney, G., James, D., et al (2017). Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism. Cell Reports, 21(12), 3536-3547. [More Information]
  • Stoeckli, J., Fisher-Wellman, K., Chaudhuri, R., Zeng, X., Fazakerley, D., Meoli, C., Thomas, K., Hoffman, N., Mangiafico, S., Xirouchaki, C., Cooney, G., James, D., et al (2017). Metabolomic analysis of insulin resistance across different mouse strains and diets. Journal of Biological Chemistry, 292(47), 19135-19145. [More Information]
  • Krycer, J., Fazakerley, D., Cater, R., Thomas, K., Naghiloo, S., Burchfield, J., Humphrey, S., Vandenberg, R., Ryan, R., James, D. (2017). The amino acid transporter SLC1A3 is plasma membrane-localised in adipocytes and its activity is insensitive to insulin. FEBS Letters, 591(2), 322-330. [More Information]

2016

  • Minard, A., Tan, S., Yang, P., Fazakerley, D., Domanova, W., Parker, B., Humphrey, S., Jothi, R., Stoeckli, J., James, D. (2016). mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes. Cell Reports, 17(1), 29-36. [More Information]
  • Kleinert, M., Parker, B., Chaudhuri, R., Fazakerley, D., Serup, A., Thomas, K., Krycer, J., Sylow Hansen, L., Fritzen, A., Hoffman, N., James, D., et al (2016). mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3. Molecular Metabolism, 5(8), 646-655. [More Information]
  • Parker, B., Thaysen-Andersen, M., Fazakerley, D., Holliday, M., Packer, N., James, D. (2016). Terminal Galactosylation and Sialylation Switching on Membrane Glycoproteins upon TNF-Alpha-Induced Insulin Resistance in Adipocytes. Molecular and Cellular Proteomics, 15(1), 141-153. [More Information]
  • Domanova, W., Krycer, J., Chaudhuri, R., Yang, P., Vafaee, F., Fazakerley, D., Humphrey, S., James, D., Kuncic, Z. (2016). Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies. PloS One, 11(6), 1-14. [More Information]

2015

  • Wu, L., Fazakerley, D., Cantley, J. (2015). Circulating AFABP promotes insulin secretion. Obesity, 23(8), 1525-2-s2.0-84937519995. [More Information]
  • Chaudhuri, R., Khoo, P., Tonks, K., Junutula, J., Kolumam, G., Modrusan, Z., Samocha-Bonet, D., Meoli, C., Hocking, S., Fazakerley, D., Stockli, J., Yang, J., James, D., et al (2015). Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity. Npj Systems Biology And Applications, 1, 1-10. [More Information]
  • Hoffman, N., Parker, B., Chaudhuri, R., Fisher-Wellman, K., Kleinert, M., Humphrey, S., Yang, P., Holliday, M., Trefely, S., Fazakerley, D., Stoeckli, J., Burchfield, J., James, D., et al (2015). Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates. Cell Metabolism, 22(5), 922-935. [More Information]
  • Koumanov, F., Pereira, V., Richardson, J., Sargent, S., Fazakerley, D., Holman, G. (2015). Insulin regulates Rab3-Noc2 complex dissociation to promote GLUT4 translocation in rat adipocytes. Diabetologia, 58(8), 1877-1886. [More Information]
  • Trefely, S., Khoo, P., Krycer, J., Chaudhuri, R., Fazakerley, D., Parker, B., Sultani, G., Lee, J., Stephan, J., Torres, E., James, D., Stoeckli, J., et al (2015). Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/IGF-1 Signalling Pathway. Journal of Biological Chemistry, 290(43), 25834-25846. [More Information]
  • Fazakerley, D., Naghiloo, S., Chaudhuri, R., Koumanov, F., Burchfield, J., Thomas, K., Krycer, J., Prior, M., Parker, B., Murrow, B., Stoeckli, J., Meoli, C., James, D., et al (2015). Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumour Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes. Journal of Biological Chemistry, 290(39), 23528-23542. [More Information]
  • Tan, S., Fisher_Wellman, K., Fazakerley, D., Ng, Y., Pant, H., Li, J., Meoli, C., Coster, A., Stoeckli, J., James, D. (2015). Selective insulin resistance in adipocytes. Journal of Biological Chemistry, 290(18), 11337-11348. [More Information]
  • Stoeckli, J., Meoli, C., Hoffman, N., Fazakerley, D., Pant, H., Cleasby, M., Ma, X., Kleinert, M., Brandon, A., Lopez, J., James, D., et al (2015). The RabGAP TBC1D1 Plays a Central Role in Exercise-Regulated Glucose Metabolism in Skeletal Muscle. Diabetes, 64(6), 1914-1922. [More Information]

2014

  • Kleinert, M., Sylow Hansen, L., Fazakerley, D., Krycer, J., Thomas, K., Oxbøll, A., Jordy, A., Jensen, T., Yang, G., Schjerling, P., James, D., et al (2014). Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo. Molecular Metabolism, 3(6), 630-641. [More Information]

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