Dr Daniel Fazakerley

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

D17 - Charles Perkins Centre
The University of Sydney


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 the 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 glucose transport. Using proteomic techniques he has revealed a range of cellular pathways that are perturbed in insulin resistance and that appear to impinge on insulin’s ability to promote glucose transport. His major focus is understanding how these protiens and pathways regulate insulin action and whether they can be targeted to overcome insulin resistance.

International links

United Kingdom

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

United Kingdom

(University of Bath) Dr Francoise Koumanov

Selected grants

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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Journals

  • 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., 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. The 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. The 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. The 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]

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., 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. The 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. The 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. The 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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