Dr Sean Humphrey

Postdoctoral 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 4315

Website Level 5 West, D17 - Charles Perkins Centre

Biographical details

Dr Sean Humprey has always been driven to understand how things work. This curiosity led him to postdoctoral research in 'proteomics' - the study of proteins using mass spectrometry. Sean has developed cutting-edge new methods to study proteins, and how they are modified in the cell by enzymes called kinases. These methods have been published in high-profile journals, including Nature Biotechnology, and are now making it possible to undertake ambitious new biological studies that were not possible before. These have ranged from understanding embryonic stem cell differentiation, through to shedding new light on the pathways involved in opioid addiction in the brain.

Research interests

Dr Humphrey’s research focuses on developing cutting-edge mass spectrometry-based methods, and their application towards collaborative research areas in the biological sciences, as well as for drug discovery. His work emphasises the development of core enabling technologies that improve the accessibility and applicability of these methods to a wider audience of researchers and scientists.

Awards and honours

  • The University of Sydney Postdoctoral Research Fellowship
  • University of Sydney Dean’s Overseas Travel Award
  • National Association of Research Fellows (NARF) of NHMRC Postdoctoral Award
  • Max-Planck Institute of Biochemistry 2015 Junior Researcher Award
  • European Molecular Biology Organization (EMBO) Long Term Fellowship
  • Garvan Institute Thesis Prize
  • Garvan Institute Castle-Harlen Award for best performance in 2nd year PhD
  • University of New South Wales School of Medical Sciences Rising Star Award (University medalist runner up)

Selected grants

2018

  • Development of a solid-phase support for the capture of phosphopeptides; Humphrey S; DVC Research/Bridging Support Grant.
  • Taking phosphoproteomics to the clinic: high-throughput and high-sensitivity technologies for mapping molecular signalling networks.; Humphrey S, James D; DVC Research/Postdoctoral Research Fellowship Scheme.
  • Regulation of energy metabolism by CaMKK2; Humphrey S; National Health and Medical Research Council (NHMRC)/Project Grants.
  • TOR control of nutrient uptake.; Humphrey S, Peterson J; Australian Research Council (ARC)/Discovery Projects (DP).

2017

  • EasyPhos: Scalable and high performace phosphoproteomics workflow; Humphrey S; DVC Research/Bridging Support Grant.

2016

  • Ultra-high pressure system for proteomic analysis of a multi-ethnic cohort to identify biomarkers for type-2 diabetes; James D, Parker B, Humphrey S; Ian Potter Foundation/Medical Research.

Selected publications

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Journals

  • Fazakerley, D., Fritzen, A., Healy (Nelson), M., Thorius, I., Cooke, K., Humphrey, S., Cooney, G., James, D. (2019). Insulin Tolerance Test under Anaesthesia to Measure Tissue-specific Insulin-stimulated Glucose Disposal. Bio-protocol, 9(2), 1-13. [More Information]
  • Yang, G., Humphrey, S., Murashige, D., Francis, D., Wang, Q., Cooke, K., Neely, G., James, D. (2019). RagC phosphorylation autoregulates mTOR complex 1. EMBO Journal, 38(3), 1-10. [More Information]
  • Humphrey, S., Karayel, O., James, D., Mann, M. (2018). High-throughput and high-sensitivity phosphoproteomics with the EasyPhos platform. Nature Protocols, 13(9), 1897-1916. [More Information]
  • Liu, J., Sharma, K., Zangrandi, L., Chen, C., Humphrey, S., Chiu, Y., Spetea, M., Liu-Chen, L., Schwarzer, C., Mann, M. (2018). In vivo brain GPCR signaling elucidated by phosphoproteomics. Science, 360(6395), 1-10. [More Information]
  • Fazakerley, D., Chaudhuri, R., Yang, P., Maghazal, G., Cooke, 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(Article number e32111), 1-38. [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 (Nelson), 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]
  • Robles, M., Humphrey, S., Mann, M. (2017). Phosphorylation Is a Central Mechanism for Circadian Control of Metabolism and Physiology. Cell Metabolism, 25(1), 118-127. [More Information]
  • Krycer, J., Fazakerley, D., Cater, R., Cooke, 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]
  • Sacco, F., Humphrey, S., Cox, J., Mischnik, M., Schulte, A., Klabunde, T., Schaefer, M., Mann, M. (2016). Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion. Nature Communications, 7, 1-13. [More Information]
  • Minard, A., Wong, M., Chaudhuri, R., Tan, S., Humphrey, S., Parker, B., Yang, J., Laybutt, D., Cooney, G., Coster, A., Stoeckli, J., James, D. (2016). Hyperactivation of the Insulin Signaling Pathway Improves Intracellular Proteostasis by Coordinately Up-regulating the Proteostatic Machinery in Adipocytes. Journal of Biological Chemistry, 291(49), 25629-25640. [More Information]
  • Yang, P., Patrick, E., Humphrey, S., Ghazanfar, S., James, D., Jothi, R., Yang, J. (2016). KinasePA: Phosphoproteomics data annotation using hypothesis driven kinase perturbation analysis. Proteomics, 16(13), 1868-1871. [More Information]
  • Zaman, S., Choudhury, M., Jiang, J., Srivastava, P., Mohanty, B., Danielson, C., Humphrey, S., Jazwinski, S., Bastia, D. (2016). Mechanism of Regulation of Intrachromatid Recombination and Long-Range Chromosome Interactions in Saccharomyces cerevisiae. Molecular and Cellular Biology, 36(10), 1451-1463. [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]
  • Yang, P., Humphrey, S., James, D., Yang, J., Jothi, R. (2016). Positive-unlabeled ensemble learning for kinase substrate prediction from dynamic phosphoproteomics data. Bioinformatics, 32(2), 252-259. [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]
  • Yang, G., Murashige, D., Humphrey, S., James, D. (2015). A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation. Cell Reports, 12(6), 937-943. [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]
  • Humphrey, S., Azimifar, S., Mann, M. (2015). High-throughput phosphoproteomics reveals in vivo insulin signaling dynamics. Nature Biotechnology, 33(9), 990-995. [More Information]
  • Chaudhuri, R., Sadrieh, A., Hoffman, N., Parker, B., Humphrey, S., Stoeckli, J., Hill, A., James, D., Yang, J. (2015). PhosphOrtholog: a web-based tool for cross-species mapping of orthologous protein post-translational modification. BMC Genomics, 16(1), 1-14. [More Information]
  • Humphrey, S., James, D., Mann, M. (2015). Protein Phosphorylation: A Major Switch Mechanism for Metabolic Regulation. Trends in Endocrinology and Metabolism, 26(12), 676-687. [More Information]
  • Parker, B., Yang, G., Humphrey, S., Chaudhuri, R., Ma, X., Peterman, S., James, D. (2015). Targeted phosphoproteomics of insulin signaling using data-independent acquisition mass spectrometry. Science Signaling, 8(380), 1-8. [More Information]
  • Humphrey, S., Yang, G., Yang, P., Fazakerley, D., Stockli, J., Yang, J., James, D. (2013). Dynamic adipocyte phosphoproteome reveals that akt directly regulates mTORC2. Cell Metabolism, 17(6), 1009-1020. [More Information]
  • Yang, P., Humphrey, S., Fazakerley, D., Prior, M., Yang, G., James, D., Yang, J. (2012). Re-Fraction: A machine learning approach for deterministic identification of protein homologues and splice variants in large-scale MS-based proteomics. Journal of Proteome Research, 11(5), 3035-3045. [More Information]
  • Davey, J., Humphrey, S., Junutula, J., Mishra, A., Lambright, D., James, D., Stockli, J. (2012). TBC1D13 is a RAB35 specific GAP that plays an important role in GLUT4 trafficking in adipocytes. Traffic, 13(10), 1429-1441. [More Information]
  • Humphrey, S., James, D. (2012). Uncaging Akt. Science Signaling, 5(223). [More Information]
  • Prior, M., Larance, M., Lawrence, R., Soul, J., Humphrey, S., Burchfield, J., Kistler, C., Davey, J., La-Borde, P., Buckley, M., James, D., et al (2011). Quantitative Proteomic Analysis of the Adipocyte Plasma Membrane. Journal of Proteome Research, 10(11), 4970-4982. [More Information]

2019

  • Fazakerley, D., Fritzen, A., Healy (Nelson), M., Thorius, I., Cooke, K., Humphrey, S., Cooney, G., James, D. (2019). Insulin Tolerance Test under Anaesthesia to Measure Tissue-specific Insulin-stimulated Glucose Disposal. Bio-protocol, 9(2), 1-13. [More Information]
  • Yang, G., Humphrey, S., Murashige, D., Francis, D., Wang, Q., Cooke, K., Neely, G., James, D. (2019). RagC phosphorylation autoregulates mTOR complex 1. EMBO Journal, 38(3), 1-10. [More Information]

2018

  • Humphrey, S., Karayel, O., James, D., Mann, M. (2018). High-throughput and high-sensitivity phosphoproteomics with the EasyPhos platform. Nature Protocols, 13(9), 1897-1916. [More Information]
  • Liu, J., Sharma, K., Zangrandi, L., Chen, C., Humphrey, S., Chiu, Y., Spetea, M., Liu-Chen, L., Schwarzer, C., Mann, M. (2018). In vivo brain GPCR signaling elucidated by phosphoproteomics. Science, 360(6395), 1-10. [More Information]
  • Fazakerley, D., Chaudhuri, R., Yang, P., Maghazal, G., Cooke, 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(Article number e32111), 1-38. [More Information]

2017

  • 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 (Nelson), 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]
  • Robles, M., Humphrey, S., Mann, M. (2017). Phosphorylation Is a Central Mechanism for Circadian Control of Metabolism and Physiology. Cell Metabolism, 25(1), 118-127. [More Information]
  • Krycer, J., Fazakerley, D., Cater, R., Cooke, 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

  • Sacco, F., Humphrey, S., Cox, J., Mischnik, M., Schulte, A., Klabunde, T., Schaefer, M., Mann, M. (2016). Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion. Nature Communications, 7, 1-13. [More Information]
  • Minard, A., Wong, M., Chaudhuri, R., Tan, S., Humphrey, S., Parker, B., Yang, J., Laybutt, D., Cooney, G., Coster, A., Stoeckli, J., James, D. (2016). Hyperactivation of the Insulin Signaling Pathway Improves Intracellular Proteostasis by Coordinately Up-regulating the Proteostatic Machinery in Adipocytes. Journal of Biological Chemistry, 291(49), 25629-25640. [More Information]
  • Yang, P., Patrick, E., Humphrey, S., Ghazanfar, S., James, D., Jothi, R., Yang, J. (2016). KinasePA: Phosphoproteomics data annotation using hypothesis driven kinase perturbation analysis. Proteomics, 16(13), 1868-1871. [More Information]
  • Zaman, S., Choudhury, M., Jiang, J., Srivastava, P., Mohanty, B., Danielson, C., Humphrey, S., Jazwinski, S., Bastia, D. (2016). Mechanism of Regulation of Intrachromatid Recombination and Long-Range Chromosome Interactions in Saccharomyces cerevisiae. Molecular and Cellular Biology, 36(10), 1451-1463. [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]
  • Yang, P., Humphrey, S., James, D., Yang, J., Jothi, R. (2016). Positive-unlabeled ensemble learning for kinase substrate prediction from dynamic phosphoproteomics data. Bioinformatics, 32(2), 252-259. [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

  • Yang, G., Murashige, D., Humphrey, S., James, D. (2015). A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation. Cell Reports, 12(6), 937-943. [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]
  • Humphrey, S., Azimifar, S., Mann, M. (2015). High-throughput phosphoproteomics reveals in vivo insulin signaling dynamics. Nature Biotechnology, 33(9), 990-995. [More Information]
  • Chaudhuri, R., Sadrieh, A., Hoffman, N., Parker, B., Humphrey, S., Stoeckli, J., Hill, A., James, D., Yang, J. (2015). PhosphOrtholog: a web-based tool for cross-species mapping of orthologous protein post-translational modification. BMC Genomics, 16(1), 1-14. [More Information]
  • Humphrey, S., James, D., Mann, M. (2015). Protein Phosphorylation: A Major Switch Mechanism for Metabolic Regulation. Trends in Endocrinology and Metabolism, 26(12), 676-687. [More Information]
  • Parker, B., Yang, G., Humphrey, S., Chaudhuri, R., Ma, X., Peterman, S., James, D. (2015). Targeted phosphoproteomics of insulin signaling using data-independent acquisition mass spectrometry. Science Signaling, 8(380), 1-8. [More Information]

2013

  • Humphrey, S., Yang, G., Yang, P., Fazakerley, D., Stockli, J., Yang, J., James, D. (2013). Dynamic adipocyte phosphoproteome reveals that akt directly regulates mTORC2. Cell Metabolism, 17(6), 1009-1020. [More Information]

2012

  • Yang, P., Humphrey, S., Fazakerley, D., Prior, M., Yang, G., James, D., Yang, J. (2012). Re-Fraction: A machine learning approach for deterministic identification of protein homologues and splice variants in large-scale MS-based proteomics. Journal of Proteome Research, 11(5), 3035-3045. [More Information]
  • Davey, J., Humphrey, S., Junutula, J., Mishra, A., Lambright, D., James, D., Stockli, J. (2012). TBC1D13 is a RAB35 specific GAP that plays an important role in GLUT4 trafficking in adipocytes. Traffic, 13(10), 1429-1441. [More Information]
  • Humphrey, S., James, D. (2012). Uncaging Akt. Science Signaling, 5(223). [More Information]

2011

  • Prior, M., Larance, M., Lawrence, R., Soul, J., Humphrey, S., Burchfield, J., Kistler, C., Davey, J., La-Borde, P., Buckley, M., James, D., et al (2011). Quantitative Proteomic Analysis of the Adipocyte Plasma Membrane. Journal of Proteome Research, 10(11), 4970-4982. [More Information]

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