ORCID Profile
0000-0002-2986-5775
Current Organisations
Western Sydney Local Health District
,
University of Sydney
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Publisher: Wiley
Date: 29-10-2020
Publisher: SAGE Publications
Date: 24-08-2017
Abstract: Mutations in the nucleotide binding domain of the PRR, NOD2, are associated with the autoinflammatory diseases Blau syndrome and early-onset sarcoidosis. Current theories suggest that constitutive activation of the NOD2 pathway may be responsible for pathogenesis of these diseases. Here, we report the phenotype of a kindred with Blau syndrome caused by a novel NOD2 mutation (p.E383D). Signaling protein and cytokine expression were examined, and the results of these experiments challenge current theories of constitutive NOD2 activation in the pathophysiology of Blau syndrome.
Publisher: Springer Science and Business Media LLC
Date: 16-10-2019
DOI: 10.1038/S41435-019-0089-5
Abstract: Epstein–Barr Virus (EBV) infection appears to be necessary for the development of Multiple Sclerosis (MS), although the specific mechanisms are unknown. More than 200 single-nucleotide polymorphisms (SNPs) are known to be associated with the risk of developing MS. About a quarter of these are also highly associated with proximal gene expression in B cells infected with EBV (lymphoblastoid cell lines—LCLs). The DNA of LCLs is hypomethylated compared with both uninfected and activated B cells. Since methylation can affect gene expression, and so cell differentiation and immune evasion, we hypothesised that EBV-driven hypomethylation may affect the interaction between EBV infection and MS. We interrogated an existing dataset comprising three in iduals with whole-genome bisulfite sequencing data from EBV transformed B cells and CD40L-activated B cells. DNA methylation surrounding MS risk SNPs associated with gene expression in LCLs (LCLeQTL) was less likely to be hypomethylated than randomly selected chromosomal regions. Differential methylation was independent of genomic features such as promoter regions, but genes preferentially expressed in EBV-infected B cells, including the LCLeQTL genes, were underrepresented in the hypomethylated regions. Our data does not indicate MS genetic risk is affected by EBV hypomethylation.
Publisher: Springer Science and Business Media LLC
Date: 04-02-2021
DOI: 10.1186/S13072-021-00383-X
Abstract: The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation and DNA methylation at vitamin D receptor binding sites in adult and paediatric myeloid cells. This was accomplished through differentiating CD34+ haematopoietic progenitors into CD14+ mononuclear phagocytes, in the presence and absence of calcitriol. Few DNA methylation changes occurred in cells treated with calcitriol. However, several VDR-binding sites demonstrated increased DNA methylation in cells of adult origin when compared to cells of paediatric origin. This phenomenon was not observed at other transcription factor binding sites. Genes associated with these sites were enriched for intracellular signalling and cell activation pathways involved in myeloid cell differentiation and adaptive immune system regulation. These results suggest vitamin D exposure at critical periods during development may contribute to latitude-related differences in autoimmune disease incidence.
Publisher: Wiley
Date: 24-04-2022
DOI: 10.5694/MJA2.51499
Publisher: Cold Spring Harbor Laboratory
Date: 03-05-2020
DOI: 10.1101/2020.05.02.073551
Abstract: Retrotransposons are genetic elements capable of their own propagation and insertion into the human genome. Because of their mutagenic potential, retrotransposons are heavily suppressed by mechanisms including DNA methylation. Increased age is associated with decreasing DNA methylation of the LINE-1 retrotransposon and may partially explain the predisposition towards malignancy with advancing age. Vitamin D has been investigated for its effects on DNA methylation at LINE-1 elements with mixed results. This study hypothesised that LINE-1 DNA methylation is altered by vitamin D exposure and age. Using whole genome bisulfite sequencing of adult and newborn haematopoietic progenitors, DNA methylation at LINE-1 elements was not found to vary between cells cultured with or without calcitriol, both in adults and newborns. In contrast, several LINE-1 regions were found to be differentially methylated between adults and children, but these were not uniformly hypermethylated in paediatric cells. The results of this study suggest that at least in haematopoietic cells, vitamin D does not appear to affect LINE-1 methylation.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.PATHOL.2016.02.001
Abstract: A commercial PLA2R Ab ELISA was validated by examining its ability to distinguish primary from secondary membranous nephropathy, correlating results with clinical markers of disease activity, and comparing its performance with an indirect immunofluorescence test (IIFT). PLA2R Ab levels were measured in 77 patients with biopsy proven membranous nephropathy, ided into either idiopathic (n = 61) or secondary groups (n = 6). In the idiopathic group, measures of contemporaneous disease activity (proteinuria, serum creatinine) were compared between seropositive and seronegative subjects. ELISA values were then compared with semi-quantitative results from an IIFT using PLA2R transfected HEK293 cells as substrate. The PLA2R Ab ELISA was positive in only 15 of 61 (25%) patients with idiopathic membranous nephropathy (IMN), but there was a significant negative relationship with time since diagnosis. Thus, in a subgroup of patients diagnosed within 6 months of analysis, the sensitivity was 6/15 (55%), rising to 6/8 (75%) in those recently-diagnosed patients who had not been treated. In the entire cohort, there was a significant positive correlation between ELISA values and degree of proteinuria, but our analysis did not control for variation of both variables with time. The PLA2R Ab ELISA also showed very high agreement with IIFT (96%). Therefore, the PLA2R Ab ELISA is a highly specific test for distinguishing primary from secondary membranous nephropathy that is most sensitive in newly diagnosed patients who have not received immunosuppression. Antibody levels correlated with degree of proteinuria, but this relationship was not shown to be independent of time. Both IIFT and ELISA platforms performed comparably.
Publisher: Cold Spring Harbor Laboratory
Date: 29-04-2020
DOI: 10.1101/2020.04.27.062075
Abstract: The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation as well as DNA methylation at vitamin D receptor binding sites in adult and paediatric myeloid cells. Very few DNA methylation changes occurred in adult and paediatric cells treated with calcitriol. However, several VDR binding sites across the genome demonstrated increased DNA methylation in cells of adult origin. Genes associated with these VDR binding sites were enriched for intracellular signalling and cell activation pathways, suggesting that age-dependent potential for myeloid cell differentiation and adaptive immune system regulation may be encoded for by DNA methylation. These results suggest vitamin D exposure at critical periods in immune system development may contribute to the well characterised latitude related differences in autoimmune disease incidence.
Publisher: Springer Science and Business Media LLC
Date: 09-10-2020
No related grants have been discovered for Lawrence Ong.