Dr Joyce Chiu
School of Medical Sciences
Faculty of Medicine and Health
Dr Joyce Chiu is a pioneer in the field of “mechano-redox biology” with her discovery of novel regulation of integrin adhesion by force and redox reactions. She has developed state-of-art proteomic methods that enable detection and quantification of redox changes in proteins at the atomic level. As an expert in redox biochemistry and cell biology, Dr Chiu has discovered novel redox regulation of thrombosis, angiogenesis, inflammation and metabolism. Her extensive experience in working with vascular thiol isomerases has led to the discovery of a new class of reversible anti-thrombotic compounds that target secreted protein disulphide isomerase. Her research has been published in top biomedical journals including Circulation Research, eLife, Nature Communications, Circulation, Trends in Cell Biology, Nucleic Acids Research, and Blood. Her discovery of novel redox regulation in cancer and thrombosis led to her award of the Helen and Robert Ellis Fellowship (2017-2019) and the Professor Tony Basten Fellowship (2018) from the Sydney Medical School Foundation. Dr Chiu has recently received the Outstanding Young Scientist Award from the Joint Symposium of the Asian Pacific Society of Thrombosis and Haemostasis and Japanese Society of Thrombosis and Haemostasis (2021) and an Oral Communication Award from the 15th World Congress on Inflammation (2022).
Disulphide bond is a chemical bond between two cysteine residues. For decades, disulphide bonds are thought to be inert structural elements that stabilise protein conformation. Emerging evidence indicates that disulphide bonds are functional and control functions in the proteins they reside. Disulphide bonds are reversible in nature such that they can be cleaved and re-formed. They are also mechano-sensitive, and twisting or bending of disulphide bonds by force can facilitate or harden their cleavage/formation. With their unique biophysical properties, disulphide bonds serve as versatile molecular switches that regulate protein functions in the vasculature. Using my proteomic methodologies, I have elucidated novel mechano-redox or redox regulation of blood coagulation, angiogenesis, inflammation and metabolism by disulphide bonds. In collaborations, my research employs bioinformatics, microfluidics, single-molecule force spectroscopy, and mouse models to interrogate mechano-redox regulation of protein functions.
1. Mechano-redox regulation of integrins
2021 - Thrombosis and Haemostasis Society of Australia and New Zealand
2019 - International Society of Thrombosis and Haemostasis
2007- present Australian Society for Biochemistry and Molecular Biology (ASBMB) Ordinary member
2022 Oral Communication Award from the 15th World Congress on Inflammation
2021 Outstanding Young Scientist Award from the Joint Symposium of the Asian Pacific Society of Thrombosis and Haemostasis and Japanese Society of Thrombosis and Haemostasis
(Harvard University) Investigation of the function of vascular thiol isomerases in thrombosis |
Publications
Journals
- Lv, K., Chen, S., Xu, X., Chiu, J., Wang, H., Han, Y., Yang, X., Bowley, S., Wang, H., Tang, Z., Ju, A., Hogg, P., et al (2024). Protein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis. Nature Communications, 15(1). [More Information]
- Kutzki, F., Butera, D., Lay, A., Maag, D., Chiu, J., Woon, H., Kubař, T., Elstner, M., Aponte-Santamaria, C., Hogg, P., et al (2023). Disulfide bond reduction and exchange in C4 domain of von Willebrand factor undermines platelet binding. Journal of Thrombosis and Haemostasis, 21(8), 2089-2100. [More Information]
- Lay, A., Dupuy, A., Hagimola, L., Tieng, J., Larance, M., Zhang, Y., Yang, J., Kong, Y., Chiu, J., Gray, E., Maclean, J., Hofma, B., Jackson, S., Hogg, P., Passam, F., et al (2023). Endoplasmic reticulum protein 5 attenuates platelet endoplasmic reticulum stress and secretion in a mouse model. Blood Advances, 7(9), 1650-1665. [More Information]
2024
- Lv, K., Chen, S., Xu, X., Chiu, J., Wang, H., Han, Y., Yang, X., Bowley, S., Wang, H., Tang, Z., Ju, A., Hogg, P., et al (2024). Protein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis. Nature Communications, 15(1). [More Information]
2023
- Kutzki, F., Butera, D., Lay, A., Maag, D., Chiu, J., Woon, H., Kubař, T., Elstner, M., Aponte-Santamaria, C., Hogg, P., et al (2023). Disulfide bond reduction and exchange in C4 domain of von Willebrand factor undermines platelet binding. Journal of Thrombosis and Haemostasis, 21(8), 2089-2100. [More Information]
- Lay, A., Dupuy, A., Hagimola, L., Tieng, J., Larance, M., Zhang, Y., Yang, J., Kong, Y., Chiu, J., Gray, E., Maclean, J., Hofma, B., Jackson, S., Hogg, P., Passam, F., et al (2023). Endoplasmic reticulum protein 5 attenuates platelet endoplasmic reticulum stress and secretion in a mouse model. Blood Advances, 7(9), 1650-1665. [More Information]
- Dupuy, A., Aponte-Santamaría, C., Yeheskel, A., Hortle, E., Oehlers, S., Grater, F., Hogg, P., Passam, F., Chiu, J. (2023). Mechano-Redox Control of Mac-1 De-Adhesion by PDI Promotes Directional Movement under Flow. Circulation Research, 132(9), E151-E168. [More Information]
2022
- Dupuy, A., Ju, A., Chiu, J., Passam, F. (2022). Mechano-Redox Control of Integrins in Thromboinflammation. Antioxidants & Redox Signaling, 37(13-15), 1072-1093. [More Information]
2021
- Pijning, A., Blyth, M., Coote, M., Passam, F., Chiu, J., Hogg, P. (2021). An alternate covalent form of platelet αIIbβ3 integrin that resides in focal adhesions and has altered function. Blood, 138(15), 1359-1372. [More Information]
- Xu, X., Chiu, J., Chen, S., Fang, C. (2021). Pathophysiological roles of cell surface and extracellular protein disulfide isomerase and their molecular mechanisms. British Journal of Pharmacology, 178(15), 2911-2930. [More Information]
2020
- Lu, Z., Chiu, J., Lee, L., Schindeler, A., Jackson, M., Ramaswamy, Y., Dunstan, C., Hogg, P., Zreiqat, H. (2020). Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7. Stem Cells Translational Medicine, 9(3), 403-415. [More Information]
2019
- Chiu, J., Hogg, P. (2019). Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation. Journal of Biological Chemistry, 294(8), 2949-2960. [More Information]
- Passam, F., Chiu, J. (2019). Allosteric disulphide bonds as reversible mechano-sensitive switches that control protein functions in the vasculature. Biophysical Reviews, 11(3), 419-430. [More Information]
- Su, Z., Burchfield, J., Yang, P., Humphrey, S., Yang, G., Francis, D., Yasmin, S., Shin, S., Norris, D., Kearney, A., Astore, M., Scavuzzo, J., Wang, Q., Parker, B., Neely, G., Vafaee, F., Chiu, J., Yeo, R., Hogg, P., Fazakerley, D., Kuyucak, S., James, D., et al (2019). Global redox proteome and phosphoproteome analysis reveals redox switch in Akt. Nature Communications, 10(1), 1-18. [More Information]
2018
- Pijning, A., Chiu, J., Yeo, R., Wong, J., Hogg, P. (2018). Identification of allosteric disulfides from labile bonds in X-ray structures. Royal Society Open Science, 5(2), 1-13. [More Information]
- Passam, F., Chiu, J., Ju, A., Pijning, A., Jahan, Z., Mor-Cohen, R., Yeheskel, A., Kolsek, K., Tharichen, L., Aponte-Santamaria, C., Hogg, P., et al (2018). Mechano-redox control of integrin de-adhesion. eLife, 7, 1-22. [More Information]
- Bekendam, R., Iyu, D., Passam, F., Stopa, J., De Ceunynck, K., Muse, O., Bendapudi, P., Garnier, C., Gopal, S., Chiu, J., Hogg, P., et al (2018). Protein disulfide isomerase regulation by nitric oxide maintains vascular quiescence and controls thrombus formation. Journal of Thrombosis and Haemostasis, 16(11), 2322-2335. [More Information]
2016
- Bekendam, R., Bendapudi, P., Lin, L., Nag, P., Pu, J., Kennedy, D., Feldenzer, A., Chiu, J., Cook, K., Furie, B., Hogg, P., et al (2016). A substrate-driven allosteric switch that enhances PDI catalytic activity. Nature Communications, 7, 1-11. [More Information]
2015
- Chiu, J., Passam, F., Butera, D., Hogg, P. (2015). Protein Disulfide Isomerase in Thrombosis. Seminars in Thrombosis and Hemostasis, 41(7), 765-773. [More Information]
2014
- Butera, D., Cook, K., Chiu, J., Wong, J., Hogg, P. (2014). Control of blood proteins by functional disulfide bonds. Blood, 123(13), 2000-2007. [More Information]
- Chiu, J., Wong, J., Gerometta, M., Hogg, P. (2014). Mechanism of dimerization of a recombinant mature vascular endothelial growth factor C. Biochemistry, 53(1), 7-9. [More Information]
- Chiu, J., Wong, J., Hogg, P. (2014). Redox Regulation of Methionine Aminopeptidase 2 Activity. Journal of Biological Chemistry, 289(21), 15035-15043. [More Information]
2013
- Ng, J., Chiu, J., Hogg, P., Wong, J. (2013). Tyrosine nitration moderates the peptidase activity of human methionyl aminopeptidase 2. Biochemical and Biophysical Research Communications, 440(1), 37-42. [More Information]
2012
- Chiu, J., Dawes, I. (2012). Redox control of cell proliferation. Trends in Cell Biology, 22(11), 592-601. [More Information]
- Park, D., Chiu, J., Perrone, G., Dilda, P., Hogg, P. (2012). The tumour metabolism inhibitors GSAO and PENAO react with cysteines 57 and 257 of mitochondrial adenine nucleotide translocase. Cancer Cell International, 12(1), 1-6. [More Information]
2011
- Chiu, J., Tactacan, C., Tan, S., Lin, R., Wouters, M., Dawes, I. (2011). Cell cycle sensing of oxidative stress in Saccharomyces cerevisiae by oxidation of a specific cysteine residue in the transcription factor Swi6p. Journal of Biological Chemistry, 286(7), 5204-5214. [More Information]
Selected Grants
2018
- Towards a novel 'mechanomedicine' against the sticky clot problem of diabetes by targeting oxidoreductase ERp5 , Chiu J, Ju A, Charles Perkins Centre/Early-Mid Career Researcher Seed Funding Grant
2017
- ERp5 is essential to thrombosis , Chiu J, Sydney Medical School/Professor Tony Basten Fellowship in Medical Genetics and Molecular Biology
- Metabolic reprogramming in cancer cells through thioredoxin activation of Akt1, Chiu J, Sydney Medical School Foundation/Helen and Robert Ellis Fellowship
In the media
https://www.canberratimes.com.au/story/8159684/cardiovascular-disease-hope-in-blood-cell-finding/
https://www.centenary.org.au/news/inflammation-presentation-awarded/
https://www.woolcock.org.au/news/young-research-stars-shine-brightly