Dr Jacky Stoeckli
Senior Research Fellow
School of Life and Environmental Sciences
I obtained my PhD from the University of Basel in 2003. During this period I was trained in Cell Biology, Molecular Biology and Biochemistry and studied protein trafficking and trafficking signals. In 2004 I joined Prof David James' group when he was at the Garvan Institute in Sydney. Initially I focused on insulin regulated protein trafficking with a particular interest in GLUT4 and the vesicle trafficking proteins, such as Rabs and RabGAPs. In the James Lab I learned about Insulin Signalling, Glucose Metabolism and Mouse Physiology. In 2015 I was appointed as a Research Fellow at the Charles Perkins Centre and the School of Life and Environmental Sciences at the University of Sydney. My group "Molecular Cell Biology" within the larger James lab focuses on the insulin regulation of lipolysis.
Adipose tissue lipolysis is induced during fasting via catecholamines and other factors to activate lipolysis to release FFA into the circulation as an energy source for other tissues.These stimuli activate lipolysis in fat cells via elevated cAMP and activation of PKA. Active PKA phosphorylates substrates like Hormone Sensitive Lipase (HSL) and the lipid droplet (LD) protein Perilipin 1 (PLIN1), releasing PLIN1 from CGI-58, leading to formation of an active complex comprising Adipose Triglyceride Lipase (ATGL) and its co-activator CGI-58. This results in LD recruitment/activation of the two lipases involved in the first two steps of lipolysis and complete hydrolysis of TG to three molecules of FFAs and one of glycerol.
Insulin suppresses lipolysis but recently gaps have emerged in our understanding of insulin regulation of lipolysis. In view of the detrimental consequences of unsuppressed lipolysis, such as insulin resistance and fatty liver disease, it is surprising how little we know about the mechanism of this process. My focus is to shed light on this process and to identify novel regulators of lipolysis.
Former UNSW PhD students:
Poh Sim Khoo (UNSW, graduated 2011)
Dave Pederson (graduated 2012)
Sean Humphrey (graduated 2013)
Sophie Trefely (graduated 2015)
Annabel Minard (graduated 2017)
Beverley Murrow (graduated 2017)
Former USYD Honours students (all 1st class Honours):
Anagha Killedar (2012)
Imogen Faulds (2015)
Gaia Herrmann (2016)
Insulin regulation of lipolysis
Novel regulators of lipolysis
Publications
Book Chapters
- Stoeckli, J., Piper, R., James, D. (2016). Regulated versus Constitutive Secretion - A Major Form of Intercellular Communication. In Not known (Eds.), Encyclopedia of Cell Biology, (pp. 376-383). TBC. [More Information]
Journals
- Diaz Vegas, A., Cooke, K., Cutler, H., Yau, B., Masson, S., Harney, D., Fuller, O., Potter, M., Madsen, S., Craw, N., Zhang, Y., Moreno, C., Kebede, M., Neely, G., Stoeckli, J., Burchfield, J., James, D. (2024). Deletion of miPEP in adipocytes protects against obesity and insulin resistance by boosting muscle metabolism. Molecular Metabolism, 86. [More Information]
- Cutler, H., Madsen, S., Masson, S., Cooke, K., Potter, M., Burchfield, J., Stoeckli, J., Nelson, M., Cooney, G., James, D. (2024). Dual Tracer Test to Measure Tissue-Specific Insulin Action in Individual Mice Identifies In Vivo Insulin Resistance Without Fasting Hyperinsulinemia. Diabetes, 73(3), 359-373. [More Information]
- Yau, B., Madsen, S., Nelson, M., Cooke, K., Fritzen, A., Thorius, I., Stoeckli, J., James, D., Kebede, M. (2024). Genetics and diet shape the relationship between islet function and whole body metabolism. American Journal of Physiology - Endocrinology and Metabolism, 326(5), E663-E672. [More Information]
2024
- Diaz Vegas, A., Cooke, K., Cutler, H., Yau, B., Masson, S., Harney, D., Fuller, O., Potter, M., Madsen, S., Craw, N., Zhang, Y., Moreno, C., Kebede, M., Neely, G., Stoeckli, J., Burchfield, J., James, D. (2024). Deletion of miPEP in adipocytes protects against obesity and insulin resistance by boosting muscle metabolism. Molecular Metabolism, 86. [More Information]
- Cutler, H., Madsen, S., Masson, S., Cooke, K., Potter, M., Burchfield, J., Stoeckli, J., Nelson, M., Cooney, G., James, D. (2024). Dual Tracer Test to Measure Tissue-Specific Insulin Action in Individual Mice Identifies In Vivo Insulin Resistance Without Fasting Hyperinsulinemia. Diabetes, 73(3), 359-373. [More Information]
- Yau, B., Madsen, S., Nelson, M., Cooke, K., Fritzen, A., Thorius, I., Stoeckli, J., James, D., Kebede, M. (2024). Genetics and diet shape the relationship between islet function and whole body metabolism. American Journal of Physiology - Endocrinology and Metabolism, 326(5), E663-E672. [More Information]
2023
- Madsen, S., Nelson, M., Deshpande, V., Humphrey, S., Cooke, K., Howell, A., Diaz Vegas, A., Burchfield, J., Stoeckli, J., James, D. (2023). Deep Proteome Profiling of White Adipose Tissue Reveals Marked Conservation and Distinct Features Between Different Anatomical Depots. Molecular and Cellular Proteomics, 22(3), 100508. [More Information]
- Masson, S., Madsen, S., Cooke, K., Potter, M., Diaz Vegas, A., Carroll, L., Thillainadesan, S., Cutler, H., Walder, K., Cooney, G., Stoeckli, J., James, D., et al (2023). Leveraging genetic diversity to identify small molecules that reverse mouse skeletal muscle insulin resistance. eLife, 12. [More Information]
2022
- Nelson, M., Madsen, S., Cooke, K., Fritzen, A., Thorius, I., Masson, S., carroll, L., Weiss, F., Seldin, M., Potter, M., Hocking, S., Fazakerley, D., Brandon, A., Thillainadesan, S., Senior, A., Cooney, G., Stoeckli, J., James, D. (2022). Systems-level analysis of insulin action in mouse strains provides insight into tissue- and pathway-specific interactions that drive insulin resistance. Cell Metabolism, 34(2), 227-239.e6. [More Information]
2021
- Farmer, T., Xie, S., Naslavsky, N., Stoeckli, J., James, D., Caplan, S. (2021). Defining the protein and lipid constituents of tubular recycling endosomes. Journal of Biological Chemistry, 296, 100190. [More Information]
- Francis, D., Ghazanfar, S., Havula, E., Krycer, J., Strbenac, D., Senior, A., Minard, A., Geddes, T., Nelson, M., Weiss, F., Stoeckli, J., Yang, J., James, D. (2021). Genome-wide analysis in Drosophila reveals diet-by-gene interactions and uncovers diet-responsive genes. G3: Genes, Genomes, Genetics, 11(10), jkab171. [More Information]
- Harney, D., Cielesh, M., Chu, R., Cooke, K., James, D., Stoeckli, J., Larance, M. (2021). Proteomics analysis of adipose depots after intermittent fasting reveals visceral fat preservation mechanisms. Cell Reports, 34(9), 108804. [More Information]
2020
- Li, Z., Weller, S., Drizyte-Miller, K., Chen, J., Krueger, E., Mehall, B., Stoeckli, J., Casey, C., Cao, H., McNiven, M. (2020). Maturation of Lipophagic Organelles in Hepatocytes Is Dependent Upon a Rab10/Dynamin-2 Complex. Hepatology, 72(2), 486-502. [More Information]
2019
- Stoeckli, J., Zadoorian, A., Cooke, K., Deshpande, V., Yau, B., Kebede, M., Humphrey, S., James, D. (2019). ABHD15 regulates adipose tissue lipolysis and hepatic lipid accumulation. Molecular Metabolism, 25, 83-94. [More Information]
- Nelson, M., Parker, B., Burchfield, J., Hoffman, N., Needham, E., Cooke, K., Naim, T., Sylow, L., Ling, N., Francis, D., Norris, D., Chaudhuri, R., Stoeckli, J., James, D., et al (2019). Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry. EMBO Journal, 38(24), 1-20. [More Information]
2018
- Burchfield, J., Kebede, M., Meoli, C., Stoeckli, J., Whitworth, P., Wright, A., Hoffman, N., Minard, A., Ma, X., Krycer, J., Nelson, M., Yau, B., Cooke, 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]
- Fazakerley, D., Minard, A., Krycer, J., Cooke, 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]
- Su, Z., Deshpande, V., James, D., Stoeckli, J. (2018). Tankyrase modulates insulin sensitivity in skeletal muscle cells by regulating the stability of GLUT4 vesicle proteins. Journal of Biological Chemistry, 293(22), 8578-8587. [More Information]
2017
- Stoeckli, J., Fisher-Wellman, K., Chaudhuri, R., Zeng, X., Fazakerley, D., Meoli, C., Cooke, 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]
2016
- Li, Z., Schulze, R., Weller, S., Krueger, E., Schott, M., Zhang, X., Casey, C., Liu, J., Stoeckli, J., James, D., et al (2016). A novel Rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets. Science Advances, 2(12), 1-16. [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]
- 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]
2015
- Chaudhuri, R., Khoo, P., Tonks, K., Junutula, J., Kolumam, G., Modrusan, Z., Samocha-Bonet, D., Meoli, C., Hocking, S., Fazakerley, D., Stoeckli, 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]
- 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]
2013
- Pedersen, D., Diakanastasis, B., Stöckli, J., Schmitz-Peiffer, C. (2013). Protein Kinase Cε Modulates Insulin Receptor Localization and Trafficking in Mouse Embryonic Fibroblasts. PloS One, 8(3). [More Information]
Selected Grants
2021
- Novel Insights into Lipid Homeostasis through analysis of Human Genetic Mutations, Stoeckli J, Diabetes Australia/Diabetes Research Grant Program
2020
- Unravelling a canonical mitochondrial stress response pathway, James D, New E, Stoeckli J, Burchfield J, Yang G, Australian Research Council (ARC)/Discovery Projects (DP)