school of clinical sciences at monash health

School of Clinical Sciences at Monash Health

Dr James Harris, PhD. Head of Laboratory Research, Rheumatology Research Group School of Clinical Sciences at Monash Health Faculty of Medicine, Nursing & Health Sciences Level 5, Block E, Clayton Victoria 3168 Australia T: +61 3 9594 5660 Email [email protected] www.monash.edu.au CRICOS Provider 00008C ABN 12 377 614 012

14th June, 2021 Report on research activities facilitated by Lions Club donations Past donations from the Lions Club have funded the purchase of a Tecan Infinite M1000 PRO multifunction plate reader and a Tecan HydoFlex plate washer, both of which are used for multiple different experimental assays within the lab, daily. This equipment has contributed to multiple projects within the lab, as well as being used by other members of the School/Department. More recently, funding from the Lions Rheumatism and Arthritis Medical Research Foundation Australia has been used to support two PhD candidates in the lab. Hasnat and Mehnaz have now both submitted their PhD Theses for examination, which will hopefully be complete later this year. Both Mehnaz and Hasnat were impacted by COVID-19 and the numerous lockdowns over the past year, but both have worked very hard to get their work completed and submitted. They have also both contributed to research publications from the lab (1, 2). Both Mehnaz and Hasnat would like to thank the Lions Rheumatism and Arthritis Medical Research Foundation Australia for helping them through their studies and training, especially in these difficult times. The pandemic and the associated lockdowns have also affected lab activities, although we have been fortunate to be able to continue our research throughout. A lot of time and effort has been spent trying to raise research funding from various sources, including the Australian and US governments, as well as many philanthropic organisations. We are currently waiting on the outcomes of these. In the meantime, our research continues to grow, with exciting projects looking at potential alternatives to steroids for the treatment of autoimmune diseases, including RA and related diseases like lupus, and discovering new understanding of how inflammation and autoimmunity are regulated in all the rheumatic diseases. These studies have garnered interest from Industrial partners that we hope may lead to fruitful collaborations in the near future. On this subject, we have also instigated new collaborations with colleagues at Monash and RMIT that are generating some very exciting new data. In particular, we have found new biology for the pro-inflammatory molecule MIF (macrophage migration inhibitory) and the anti-inflammatory molecule GILZ (glucocorticoid-induced leucine zipper) that have potential for future therapeutic development in a range of diseases, including arthritis and lupus. We are also investigating a new compound (derived from a common dietary ingredient) that inhibits MIF and working with a company based in Belgium to test some of their new MIF-targeting drugs in our assays, based on new biology for MIF that we discovered. In addition, our clinical teams have continued their important work, publishing a number of articles, including some on the impacts of COVID-19 on patients with rheumatic diseases (3-7). In addition, the connections between the lab and clinical teams continue to grow, with a number of large research proposals submitted to study patients, as well as children with inflammatory diseases.

Mehnaz Pervin

Md Abul Hasnat



The most recent donation from the Lions Rheumatism and Arthritis Medical Research Foundation Australia will help us to purchase specialist kits for measuring levels of type I IFNs in biological tissues, including blood and cell culture supernatants from lab experiments. Type I IFNs are a group of molecules that regulate immune responses, particularly to viral infections, but also have pathological roles to play in autoimmune diseases. Studies in our lab have shown that our two favourite molecules, GILZ and MIF, can both regulate levels of type I IFNs, which may represent critical mechanisms of inflammation that could be targeted therapeutically. Thus, this kind donation will benefit a number of studies directly and help us to work out exactly how GILZ and MIF influence type I IFNs and how we might then use that to develop new therapies. Selected Recent Publications from the Monash Rheumatology Research Group 1. Dankers, W., Hasnat, Md. A., Swann, V., Alharbi, A., Lee, J. P. W., Cristofaro, M. A., Gantier, M. P.,

Jones, S. A., Morand, E. F., Flynn, J. A. & Harris, J. (2020). Necrotic cell death increases the release of macrophage migration inhibitory factor (MIF) by monocytes/macrophages. Immunology and Cell Biology 98, 782-790.

2. Nataraja, C., Dankers, W., Flynn, J., Lee, J. P. W., Zhu, W., Vincent, F. B., Gearing, L. J., Ooi, J., Pervin, M., Cristofaro, M. A., Sherlock, R., Hasnat, Md. A., Harris, J., Morand, E. F. & Jones, S. A. (2021). GILZ regulates the expression of pro-inflammatory cytokines against end-organ damage in a model of lupus. Frontiers in Immunology 12, 652800.

3. Northcott, M., Gearing, L. J., Nim, H. T., Nataraja, C., Hertzog, P. J., Jones, S. A. & Morand, E. F. (2021).

Glucocorticoid gene signatures in systemic lupus erythematosus and the effects of type I IFN: a cross-sectional and in vitro study. Lancet Rheumatology DOI:10.1016/S2665-9913(21)00006-0.

4. Robinson, P. & Morand, E. F. (2021). Divergent effects of acute versus chronic glucocorticoids in

COVID-19. Lancet Rheumatology 3, e168-e170.

5. Stuart, R. L., Zhu, W., Morand, E. F. & Stripp, A (2020). Breaking the chain of transmission within a tertiary health service: An approach to contact tracing during the COVID-19 pandemic. Infection Disease and Health doi: 10.1016/j.idh.2020.11.003.

6. Wang, D., Yeo, A. L., Dendle, C., Morton, S., Morand, E. F. & Leech, M (2020). Severe infections remain

common in a real-world rheumatoid arthritis cohort: A simple clinical model to predict infection risk. European Journal of Rheumatology doi: 10.5152/eurjrheum.2020.20172.

7. Antony, A., Connelly, K., De Silva, T., Eades, L., Tillett, W., Ayoub, S. & Morand, E. F. (2020).

Perspectives of patients with inflammatory rheumatic diseases in the early phase of COVID-19. Arthritis Care and Research 72, 1189-1195



Recent News stories from the lab Trailblazing women immunologists of Australia and New Zealand 29 April 2021

L–R: Professor Katharina Gaus, Professor Barbara Heslop, Professor Margaret Baird, Miss Dora Lush, Dr Margaret Holmes and Miss F Eleanor Williams MBE ARRC. The authors were unable to obtain photos of Dr Lucy M Bryce CBE and Dr Hildred Butler. Image: Immunol Cell Biol.

Dr Jess Borger, Catriona Nguyen-Robertson and Dr James Harris, have published an essay on trailblazing women immunologists of Australia and New Zealand.

The editorial and issue put a spotlight on the groundbreaking work of female immunologist over the last 100 years, as well as highlighting the difficulties/inequity still faced by women in Science and Immunology. The work has received considerable attention on social media. The authors Dr Jess Borger (Central Clinical School), Catriona Nguyen-Robertson (University of Melbourne) and Dr James Harris were inspired by the recent passing of Katarina Gaus (University of NSW).

The special issue and editorial which has captured international attention discusses important contributions to immunology research made by women in Australia and New Zealand over the past 100 years and highlights the difficulties women scientists have faced - and continue to face.

Dr James Harris said, "This is an important read for all immunologists (and scientist and clinicians)".

See their lively, informative essay in the journal Immunology and Cell Biology, where they have pulled together previously scattered or difficult to locate information to showcase the achievements of these outstanding female immunologists.

Borger JG, Nguyen-Robertson CV, Harris J. Trailblazing women immunologists of Australia and New Zealand. Immunol Cell Biol. 2021 Apr;99(4):338-343. doi: 10.1111/imcb.12454. PMID: 33860547.



Janssen-Cilag Medical Grant to help investigate lupus in Indigenous Australians By VITHYA PREMKUMAR 25 January 2021

Dr Fabien Vincent

School of Clinical Sciences at Monash Health researcher Dr Fabien Vincent receives a $15,000 Janssen-Cilag Pty Ltd Medical Grant for his vital research into systemic lupus erythematosus (SLE, or lupus).

Lupus is an incurable autoimmune illness affecting more than 5 million people worldwide. Lupus is more common and severe in Indigenous Australians, but the reason for this is not known.

To understand this better, Dr Vincent and his team (Rheumatology Group, Centre for Inflammatory Diseases) will establish the first national registry and biobank of Indigenous Australian lupus, nested within the Australian Lupus Registry & Biobank (ALRB), and create the first collection of clinical and biological profiles data on lupus in Indigenous Australians available in the public domain, establishing a resource for clinical applications beyond the life of this research program.

Thousands of genes and proteins in the blood will be measured from blood samples and using complex data analysis methods, known as bioinformatics, the ‘stack’ of these blood markers will be analysed.



Dr Vincent said, "This study will be a first in Indigenous Australians with lupus, and will help in identifying the right drug for the right patient. Understanding lupus at this level will expedite changes affecting the management and treatment, resulting in personalised and targeted therapies to improve the health of Indigenous Australians".

"Funding from the Janssen-Cilag Pty Ltd Medical Grant will be of invaluable help to carry out this research program to identify the biological profile of Indigenous Australians with lupus".



Dr Vera Golder receives Henry Krum Early Career Researcher Publication Prize By VITHYA PREMKUMAR 02 September 2020

Dr Vera Golder

Congratulations to Dr Vera Golder on receiving the Henry Krum Early Career Researcher Publication Prize for Clinical Sciences.

"I am deeply honoured to receive the Henry Krum Prize for Clinical Sciences. First and foremost, this body of work would not have been possible without the tremendous effort, collaboration and comradery of the researchers from the Asia Pacific Lupus Collaboration, for this I thank you. The winning publication is the culmination of 4 years of work to develop and validate an attainable clinical treatment target for systemic lupus erythematosus (SLE) - the Lupus Low Disease Activity State (LLDAS). The majority of patients were able to attain LLDAS for at least one clinical visit, and even a single visit in LLDAS was highly protective against accrual of irreversible end organ damage, a major driver of premature mortality in SLE. Not only are the results of this study practice changing, but also have a significant impact on the design of clinical trials in SLE", said Dr Golder.

school of clinical sciences at monash health

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