Sutton Arthritis Research Laboratory

Dr Lara Bereza-Malcolm, PhD

Henry Langley Postdoctoral research fellow

Dr Haiyan Lin, MD

Research assistant

https://ibjr.sydney.edu.au/

Activated protein C for chronic wound healing and the treatment of burns

• Activated protein C is a promising wound healing agent demonstrated by a decade’s research led by Professor Chris Jackson, the director of the Sutton Arthritis Research Laboratory.
• This project is investigating the effects of a mutant form of activated protein C and its ability to promoting wound healing.
• The underlying mechanisms of this activated protein C will be tested using skin cells and mouse models.
• These studies will promote the translation of activated protein C from the lab to clinical applications.

Activated protein C as a treatment for inflammatory arthritis

• This project is exploring the therapeutical potential of activated protein C and its small peptides on inflammatory arthritis.
• These peptides (a shortened form of the protein) can mimic activated protein C’s ability to protect cells without the anti-coagulant activity that occurs with activated protein C.
• The effects of activated protein C and its small peptides will be explored using immune cells, blood vessel cells (endothelial cells), joint synovial cells (synovial fibroblasts), and cartilage (chondrocytes).

Predictive biomarkers for effective treatment of rheumatoid arthritis

• Whilst biologic therapies have significantly improved prospects for rheumatoid arthritis patients, 40% of patients fail to respond fully.
• Currently it is not possible to predict which patients will respond to which biologic therapy. In most cases, the choice of biologics is based on trial‐and‐error.
• Additionally, a full response is not observed until patients have been provided continuous treatment for months. This means that if the first biologic chosen does not work, the patient may suffer extended periods of active disease.
• In this project, the responses of rheumatoid arthritis patients’ own cells to biologic treatments (used alone or in combination with our new therapy) will be measured. These in vitro response patterns will be used to predict how well a biologic will work for each individual patient.

The function of protease activated receptor-1 and 2 in the onset and development of rheumatoid arthritis

• There is a growing awareness of the role of microbiota (bacteria, fungi and/or viruses) in the onset, severity and progression of rheumatoid arthritis, as well as its impact on the therapeutic management of these patients.
• Protease activated receptor (PAR) 1 and 2 are receptors located on human cells, strongly implicated in joint inflammation and destruction. Recently these receptors have been proposed to respond to microbial infection.
• This project will investigate how these receptors affect the onset and development of rheumatoid arthritis using immune cells from rheumatoid arthritis patients and animal arthritis disease models. In addition, composition of the microbiome in rheumatoid arthritis patients and healthy individuals will be identified.
• This data will lead to the development of new therapeutic interventions to prevent disease progression and improve the overall outlook of rheumatoid arthritis patients.

• Beserra FP, Vieira AJ, Gushiken LFS, de Souza EO, Hussni MF, Hussni CA, Nóbrega RH, Martinez ERM, Jackson CJ, de Azevedo Maia GL, Rozza AL, Pellizzon CH. Oxid Lupeol, a Dietary Triterpene, Enhances Wound Healing in Streptozotocin-Induced Hyperglycemic Rats with Modulatory Effects on Inflammation, Oxidative Stress, and Angiogenesis. Med Cell Longev. 2019 May 9;2019:3182627. doi: 10.1155/2019/3182627. eCollection 2019.
• Xue M, Zhao R, Lin H, Jackson CJ. Biological molecule delivery for the treatment of chronic cutaneous wounds and scars. Adv Drug Deliv Rev. 2018 Apr;129:219-241.
• Peng Q, Luo A, Zhou Z, Xuan W, Qiu M, Wu Q, Xu L, Kong X, Zhang M, Tan W, Xue M, Wang F. Interleukin 29 inhibits RANKL-induced osteoclastogenesis via activation of JNK and STAT, and inhibition of NF-κB and NFATc1. Cytokine. 2018 Jul 9. pii: S1043-4666(18)30282-5.
• Ruilong Zhao, Christopher John Jackson, and Meilang Xue, Extracellular Matrix and Other Factors that Impact on Cutaneous. Recent Clinical Techniques, Results, and Research in Wounds book series, page 1-44. Springer. https://link.springer.com/chapter/10.1007/15695_2018_132
• Hai Po Helena Liang, Joshua Xu, Meilang Xue and Christopher J Jackson Matrix metalloproteinases in bone development and pathology: current knowledge and potential clinical utility. Metalloproteinases In Medicine (Dovepress): 2016:3:93-102.

http://sydney.edu.au/medicine/people/academics/profiles/meilang.xue.php#publications-by-year

http://sydney.edu.au/medicine/people/academics/profiles/chris.jackson.php#publications-by-year

https://sydney.edu.au/medicine/people/academics/profiles/lara.bereza-malcolm.php#publications-by-year