Projects per year
Personal profile
Research interests
To understand pathophysiology of diabetes associated injury in kidney and blood vessels in order to identify and validate new molecular targets for development of novel therapeutic agents to prevent, retard and treat diabetic complications such as diabetic nephropathy and diabetes associated vascular disease.
We initially identified and cloned Cell Division Autoantigen 1 (CDA1). After an extensive study on CDA1 biology, including using cultured cells, laboratory animals and clinical biopsy samples, we have now established a pivotal role for CDA1 in the pathogenesis of diabetic nephropathy (DN), a life threatening kidney disease that occurs in a significant number of diabetic subjects. Our primary finding suggests that CDA1 is a potential drug target to combat DN. As a strategy to pharmacologically target CDA1, we have recently developed a prototype peptide inhibitor, named CHA-061, which can reduce renal injury in a mouse model of DN.
We are now focusing on comprehensively assessing CHA-061 in several DN models relevant to both type 1 and type 2 diabetes. These studies will further validate CDA1 pathway as an efficacious and potentially safe drug target with the new data from these studies serving as a comparison point for evaluating new inhibitors.
We are currently collaborating with experts in multidisciplinary fields from The Monash Institute of Pharmaceutical Sciences (MIPS) and CSIRO to further improve the performance of CHA-061 as well as to convert it to a small molecule inhibitor. Our research approaches include molecular biology, cell biology, protein chemistry, crystallography, structure based design and modification of peptide and small molecule inhibitors as well as preclinical animal studies.
Supervision interests
Projects and Opportunities
Honours, Masters and PhD research projects are available in the laboratory. Please contact us to discuss the details of the projects and to see how they fit in your specific interests. Please refer to the following general description of our current projects.
Project 1: Characterization of the prototype inhibitor of CDA1, CHA-061, in diabetic nephropathy in Akita mice
Description: This project seeks to comprehensively characterize our prototype inhibitor of CDA1, CHA-061, for its treatment effect on diabetes associated kidney disease in Akita diabetic mice. The Akita mouse (Ins2Akita) harbours a mutation in the insulin 2 gene (Ins2C96Y), leading to impaired insulin secretion. This mouse model of diabetes with insulin insufficiency is relevant to type 1 (juvenile onset) diabetes as seen in clinical practice. The heterozygous Akita mice are viable and fertile, and develop hyperglycaemia, hypoinsulinemia, polydipsia and polyuria at 3-4 weeks of age. Renal injury in association with diabetes at 4-6 months of age becomes overt with a marked increase in albuminuria, development of renal fibrosis accompanied by a series of histological, molecular and biochemical changes. Akita diabetic and WT non-diabetic control mice will be treated with our CDA1 inhibitor at the age of 8 or 16 weeks for 10 weeks before being killed at the age of 4 and 6 months, respectively, for analysis of relevant renal endpoints. Dedicated animal technicians are available to assist students with animal handling and caring. Senior researchers and fellow students are also available in the lab to guide and assist with performing a broad range of laboratory experiments. This includes analysis of biological samples involving the use of molecular, biochemical and histological techniques to measure expression levels of specific genes implicated in the functional and structural features of diabetic kidney disease as well as assessing relevant signaling molecules. In vitro studies including the use of cultured cells will also be performed to complement the in vivo findings and to further delineate the molecular mechanisms underlying the action of the inhibitor.
Project 2: Characterization of the prototype inhibitor of CDA1, CHA-061, in diabetic nephropathy in db/db mice
Description: This project seeks to comprehensively characterize our prototype inhibitor of CDA1, CHA-061, for its treatment effect on diabetes associated kidney disease in db/db diabetic mice. The db/db mouse has a mutation in leptin receptor, which leads to obesity and onset of diabetes at the age of 3-4 weeks, with typical features of DN such as albuminuria, renal fibrosis and glomerular sclerotic injury seen at 16-18 weeks of age. This mouse model of diabetes is relevant to the most common form of diabetes seen in clinical practice, type 2 (maturity onset) diabetes. Diabetic db/db and control db/h mice will be treated with the prototype inhibitor, CHA-061, at the age of 8 or 16 weeks for 10 weeks. Relevant renal endpoints of these mice will be analyzed. Dedicated animal technicians are available to assist students with animal handling and caring. Senior researchers and fellow students are also available in the lab to guide and assist with performing a broad range of laboratory experiments. This includes analysis of biological samples involving the use of molecular, biochemical and histological techniques to measure expression levels of specific genes implicated in the functional and structural features of diabetic kidney disease as well as assessing relevant signaling molecules. In vitro studies including the use of cultured cells will also be performed to complement the in vivo findings and to further delineate the molecular mechanisms underlying the action of the inhibitor.
Project 3: To improve the potency of CHA-061, the prototype peptide inhibitor of CDA1
Description: This project seeks to further improve the behavior of our prototype peptide inhibitor CHA-061 against the profibrotic effect of CDA1. CHA-061 is a Retro Inverso D amino acid peptide containing a short sequence of a newly identified CDA1 binding protein and a previously described “Cell Penetrating Peptide” (CPP). The CDA1 binding protein part of the CHA-061 inhibitor competitively binds to CDA1 leading to inhibition of formation of the CDA1 complex with its key binding partner protein in the cells. The CPP part of CHA-061 assists with cellular entry of the inhibitor. The theme of this project is to modify this prototype peptide inhibitor and/or to convert it, based on the structure of the CDA1/CHA-061 binding interface, to a new orally bioavailable small molecule inhibitor. The approaches include screening residue substitution derivative peptides using relevant assays (both cell-free and cell based assays), solving CDA1/CHA-061 binding structures by crystallography, medicinal chemistry modification and screening for low molecular weight chemical fragments which bind to CDA1 (Fragment-based Lead Discovery, or FBLD). This is an ideal project for a researcher interested in pharmacology, structural biology and drug discovery.
Monash teaching commitment
Supervision:
>25 Research students, including Honors, Masters, PhD students and overseas visiting scientists
Examiner:
Honors, Masters, PhD thesis examination for University of Melbourne, University of Sydney, RMIT University, University of Queensland
Chief Examiner and coordinator:
Monash University Masters and PhD course unit TRM5007/TRM6007 (2021 - Present)
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
Molecular Biology, PhD, Deakin University
1991 → 1995
MVetS, Nanjing Agricultural University
1983 → 1986
External positions
Head, Laboratory of Cell Proliferation and Fibrosis in Diabetic Complications Diabetes and Metabolism Division, , Baker Heart and Diabetes Institute
2006 → 2016
Senior Research Officer, Baker Heart and Diabetes Institute
2004 → 2005
Research area keywords
- Diabetes
- Pathophysiology
- Diabetic Complications
- Diabetic Nephropathy
- Renal Fibrosis
- Diabetic Vascular Disease
- Cell Division Autoantigen 1 (CDA1)
- Transforming Growth Factor-beta (TGF-β)
Collaborations and top research areas from the last five years
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New strategy to safely and effectively reduce diabetic kidney disease
Chai, Z.-L. (Primary Chief Investigator (PCI)), Chalmers, D. (Chief Investigator (CI)) & Cooper, M. (Associate Investigator (AI))
1/01/22 → 31/12/25
Project: Research
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Development and Practical Clinical Translation of New Diagnostic and Prognostic Markers of COVID-19 and Long COVID
Nicholson, J. K. (Chief Investigator (CI)), Holmes, E. (Chief Investigator (CI)), Wist, J. (Chief Investigator (CI)), Chai, Z.-L. (Chief Investigator (CI)) & Zimmet, P. (Chief Investigator (CI))
Project: Research
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Molecular phenomic approaches to improve understanding of Post-Acute COVID-19 Syndrome – a biomarker-augmented strategy for risk based stratification and targeted intervention to improve clinical outcomes
Nicholson, J. K. (Primary Chief Investigator (PCI)), Holmes, E. (Chief Investigator (CI)), Richards, T. (Chief Investigator (CI)), Zimmet, P. (Chief Investigator (CI)), Yeap, B. B. (Chief Investigator (CI)), Wist, J. (Chief Investigator (CI)), Chai, Z.-L. (Chief Investigator (CI)) & Su, J. (Chief Investigator (CI))
1/01/22 → 31/12/24
Project: Research
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Sweet Diabetes Fund
Chai, Z.-L. (Primary Chief Investigator (PCI)) & Cooper, M. (Chief Investigator (CI))
22/12/21 → 22/12/22
Project: Research
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Strategical Expansion of Australian Excellency of Diabetes Research via practical connection and cooperation in China
Chai, Z.-L. (Primary Chief Investigator (PCI)), Zimmet, P. (Chief Investigator (CI)), Jandeleit-Dahm, K. (Chief Investigator (CI)), Slattery, R. (Chief Investigator (CI)), Zhang, L. (Chief Investigator (CI)), Liu, Z. (Chief Investigator (CI)) & Bu, P. (Chief Investigator (CI))
1/10/21 → 31/12/24
Project: Research
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The circadian syndrome is a predictor for cognition impairment in middle-aged adults: Comparison with the metabolic syndrome
Shi, Z., Stern, N., Liu, J., Tuomilehto, J., Kronfeld-Schor, N., El-Osta, A., Alberti, G., Chai, Z., Bilu, C., Einat, H., Marcus, Y. & Zimmet, P., Jul 2024, In: Diabetes/Metabolism Research and Reviews. 40, 5, 11 p., e3827.Research output: Contribution to journal › Article › Research › peer-review
Open Access6 Citations (Scopus) -
Association between Covid-19 vaccination and incidence of type 1 diabetes in China: Evidence from 14.14 million registered residents between 2007 and 2021
Liu, C., Guo, M.-N., Chai, Z., Xin, Z., Chen, G., Zimmet, P. Z. & Yang, J.-K., Jul 2023, In: Diabetes Research and Clinical Practice. 201, 5 p., 110723.Research output: Contribution to journal › Article › Research › peer-review
Open Access4 Citations (Scopus) -
Global Diabetes Prevalence in COVID-19 Patients and Contribution to COVID-19–Related Severity and Mortality: A Systematic Review and Meta-analysis
Li, R., Shen, M., Yang, Q., Fairley, C. K., Chai, Z., McIntyre, R., Ong, J. J., Liu, H., Lu, P., Hu, W., Zou, Z., Li, Z., He, S., Zhuang, G. & Zhang, L., Apr 2023, In: Diabetes Care. 46, 4, p. 890-897 8 p.Research output: Contribution to journal › Review Article › Research › peer-review
Open Access42 Citations (Scopus) -
Moxonidine Increases Uptake of Oxidised Low-Density Lipoprotein in Cultured Vascular Smooth Muscle Cells and Inhibits Atherosclerosis in Apolipoprotein E-Deficient Mice
Wang, Y., Nguyen, D. T., Anesi, J., Alramahi, A., Witting, P. K., Chai, Z., Khan, A. W., Kelly, J., Denton, K. M. & Golledge, J., Feb 2023, In: International Journal of Molecular Sciences. 24, 4, 15 p., 3857.Research output: Contribution to journal › Article › Research › peer-review
Open Access9 Citations (Scopus) -
Projected rapid growth in diabetes disease burden and economic burden in China: a spatio-temporal study from 2020 to 2030
Liu, J., Liu, M., Chai, Z., Li, C., Wang, Y., Shen, M., Zhuang, G. & Zhang, L., Apr 2023, In: The Lancet Regional Health - Western Pacific. 33, 11 p., 100700.Research output: Contribution to journal › Article › Research › peer-review
Open Access112 Citations (Scopus)
Activities
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Yuxiang Liu
Chai, Z.-L. (Host)
26 Apr 2024Activity: Hosting a visitor types › Hosting an academic or industry visitor
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Hua Tian
Chai, Z.-L. (Host)
4 Jan 2023 → 31 Dec 2023Activity: Hosting a visitor types › Hosting an academic or industry visitor
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Yue-han Wei
Chai, Z.-L. (Host)
1 Dec 2022 → 30 Jun 2023Activity: Hosting a visitor types › Hosting an academic or industry visitor
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Frontiers in Medicine (Journal)
Chai, Z.-L. (Associate editor)
2022 → …Activity: Publication peer-review and editorial work types › Editorial responsibility
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Yuxin Yang
Chai, Z.-L. (Host)
1 Aug 2019 → 31 Dec 2020Activity: Hosting a visitor types › Hosting an academic or industry visitor