Sherman Leung

BSc (Hons), PhD

Honorary Research Fellow (UQ), Clinical Team Leader (Nucleus Network)

    Research Themes

    Immunology and Bone
    Microbiome, Infection and Chronic Disease
    Pharmaco­therapeutics

    My Research

    Passionate about cutting-edge medical research — I lead a clinical research team at Nucleus Network for early phase clinical trials. Historically, my research interests include diabetes, immunology and the human gut microbiome.

    Projects

    Receptor for advanced glycation end products (RAGE) in type 1 diabetes (T1D)

    Type 1 diabetes (T1D) is an autoimmune disease which leads to the destruction of the pancreatic beta cells and a requirement for exogenous insulin treatment. Numerous genetic and environmental risk factors have been associated with T1D but, of high interest, is a potential role for the immunoglobulin superfamily glycoprotein named the receptor for advanced glycation end products (RAGE). RAGE is a pattern recognition receptor which binds a wide variety of ligands including well characterised immunomodulatory compounds including HMGB1 and LPS, but also a heterogeneous class of post-translationally modified peptides, lipids and nucleic acids named advanced glycation end products (AGEs). Interestingly, dietary AGEs have been postulated to modulate the gut microbiome as well as transverse into the circulation leading to increased circulating AGEs, which are an independent predictor for progression to T1D in children. To this end, the modern Western diet has a tendency to be enriched in dietary AGEs which are irreversibly formed through the heating and processing of foods. Clearly, RAGE is a highly interesting target which deserves further investigation in T1D.

    Human faecal metagenomic sequencing

    The human gut microbiome has been associated with general health and wellbeing, as well as several disease indications including diabetes, obesity, cardiovascular disease, colorectal cancer, Parkinson's Disease, autism spectrum disorder and inflammatory bowel disease. Metagenomics is an unbiased and comprehensive technology for assessing the relative abundances of microbial communities and their associated genes, as compared with culture-dependent analysis techniques and 16S rRNA sequencing which provide a limited amount of data and taxonomic accuracy. Human gut metagenomics is a fundamental area of expertise at Microba in which it is utilised in Microba's research and development pipelines as well as for servicing external clients and collaborators. Of high relevance, Microba has developed an end-to-end research service for external use in which human faeces is collected using a liquid-free proprietary sampling device that does not require cold chain storage for up to four weeks, which greatly assists with participant compliance in clinical trials and cost minimisation from ambient specimen transport. Microba's sequencing laboratory, world leading bioinformatics classifiers and bespoke bioinformatics reports are also included in the end-to-end research service. Please contact [email protected] for further information regarding this service which is fit for purpose in clinical trials.

    Type 1 diabetes, and the role of the RAGE receptor in disease development

    Publications

    Le Bagge S, Fotheringham A, Leung S, Forbes K (2020), Targeting the receptor for advanced glycation end products (RAGE) in type 1 diabetes, Medicinal Research Reviews, doi:10.1002/med.21654

    Leung S, Borg J, McCarthy D, Boursalian T, Cracraft J, Zhuang A, Fotheringham A, Flemming N, Watkins T, Miles J, Per-Henrik G, Scheijen J, Schalkwijk C, Steptoe R, Radford K, Knip M, Forbes J (2020), Expansion of functional regulatory T cells using soluble RAGE prevents type 1 diabetes, bioRxiv, doi:10.1101/2020.01.10.902627

    Zhuang A, Yap F, McCarthy D, Leung S, Penfold S, Leung C, Sourris K, Harcourt B, Thallas-Bonke V, Coughlan M, Schulz B, Forbes J (2019), Globally elevating the AGE clearance receptor, OST48, does not protect against the development of diabetic kidney disease, despite improving insulin secretion, bioRxiv, doi:10.1101/710558

    Leung S, Forbes M, Borg J (2016), Receptor for advanced glycation end products (RAGE) in type 1 diabetes pathogenesis, Current Diabetes Reports, 16(100), doi:10.1007/s11892-016-0782-y

    Leung S, Borg D, McCarthy D, Zhuang A, Fotheringham A, Di Trapani G, Groop P-H, Knip M, Forbes J (2015), Human soluble receptor for advanced glycation end products therapy reduces autoimmune diabetes in the non-obese diabetic mouse, Pediatric Diabetes, 16(S21), doi:10.1111/pedi.12309  

    Leung S, Borg D, Zhuang A, Fotheringham A, McCarthy D, Di Trapani G, Groop P-H, Knip M, Forbes J (2015), Delivery of recombinant human soluble receptor for advanced glycation end products delays autoimmune diabetes in the NOD mouse model, Diabetologia, 58(S1), doi:10.1007/s00125-015-3687-4

    Leung S, Borg D, McCarthy D, Zhuang A, Ward M, Forbes J (2015), Recombinant human soluble receptor for advanced glycation end product therapy reduces autoimmune diabetes in the NOD mouse model, Diabetes, 64(S1), doi:10.2337/db15-1801-1846

    Leung, S, Borg D, Paul M, Sharland A, Forbes J (2015), Gene therapy using recombinant adeno-associated virus serotype 2/8 liver-directed expression of sRAGE in experimental type 1 diabetes, Journal of Gene Medicine, 17, doi:10.1002/jgm.2834

    Research fields

    Diabetes; T cells; pancreatic islets; gene therapies; adeno-associated virus; AAV; glucagon; receptor for advanced glycation end products; RAGE

    Connect

    ORCID