2024 |
Amin M, Al-Iedani O, Lea RA, Brilot F, Maltby VE, Lechner-Scott J, 'A longitudinal analysis of brain volume changes in myelin oligodendrocyte glycoprotein antibody-associated disease.', J Neuroimaging, 34 78-85 (2024) [C1]
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Nova |
2024 |
Al-Iedani O, Lea S, Alshehri A, Maltby VE, Saugbjerg B, Ramadan S, et al., 'Multi-modal neuroimaging signatures predict cognitive decline in multiple sclerosis: A 5-year longitudinal study.', Mult Scler Relat Disord, 81 105379 (2024) [C1]
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Nova |
2023 |
Temperley IA, Seldon AN, Reckord MAW, Yarad CA, Islam FT, Duncanson K, et al., 'Dairy and gluten in disease activity in multiple sclerosis', Multiple Sclerosis Journal - Experimental, Translational and Clinical, 9 (2023) [C1]
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Nova |
2023 |
Lechner-Scott J, Maltby V, Giovannoni G, Hawkes C, Levy M, Yeh A, 'Are we there yet? The holy grail: A biomarker for Multiple Sclerosis', MULTIPLE SCLEROSIS AND RELATED DISORDERS, 78 (2023)
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2023 |
Xavier A, Campagna MP, Maltby VEE, Kilpatrick T, Taylor BVV, Butzkueven H, et al., 'Interferon beta treatment is a potent and targeted epigenetic modifier in multiple sclerosis', FRONTIERS IN IMMUNOLOGY, 14 (2023) [C1]
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Nova |
2023 |
Campagna MP, Lechner-Scott J, Maltby VE, Lea RA, Butzkueven H, Jokubaitis VG, 'Conceiving complexity: Biological mechanisms underpinning the lasting effect of pregnancy on multiple sclerosis outcomes.', Autoimmun Rev, 22 103388 (2023) [C1]
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Nova |
2023 |
Maltby V, Xavier A, Ewing E, Campagna M-P, Sampangi S, Scott RJ, et al., 'Evaluation of Cell-Specific Epigenetic Age Acceleration in People With Multiple Sclerosis.', Neurology, 101 e679-e689 (2023) [C1]
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Nova |
2023 |
Campagna MP, Xavier A, Stankovich J, Maltby VE, Slee M, Yeh WZ, et al., 'Parity is associated with long-term differences in DNA methylation at genes related to neural plasticity in multiple sclerosis', Clinical Epigenetics, 15 (2023) [C1]
Background: Pregnancy in women with multiple sclerosis (wwMS) is associated with a reduction of long-term disability progression. The mechanism that drives this effect is unknown,... [more]
Background: Pregnancy in women with multiple sclerosis (wwMS) is associated with a reduction of long-term disability progression. The mechanism that drives this effect is unknown, but converging evidence suggests a role for epigenetic mechanisms altering immune and/or central nervous system function. In this study, we aimed to identify whole blood and immune cell-specific DNA methylation patterns associated with parity in relapse-onset MS. Results: We investigated the association between whole blood and immune cell-type-specific genome-wide methylation patterns and parity in 192 women with relapse-onset MS, matched for age and disease severity. The median time from last pregnancy to blood collection was 16.7¿years (range = 1.5¿44.4¿years). We identified 2965 differentially methylated positions in whole blood, 68.5% of which were hypermethylated in parous women; together with two differentially methylated regions on Chromosomes 17 and 19 which mapped to TMC8 and ZNF577, respectively. Our findings validated 22 DMPs and 366 differentially methylated genes from existing literature on epigenetic changes associated with parity in wwMS. Differentially methylated genes in whole blood were enriched in neuronal structure and growth-related pathways. Immune cell-type-specific analysis using cell-type proportion estimates from statistical deconvolution of whole blood revealed further differential methylation in T cells specifically (four in CD4+ and eight in CD8+ T cells). We further identified reduced methylation age acceleration in parous women, demonstrating slower biological aging compared to nulligravida women. Conclusion: Differential methylation at genes related to neural plasticity offers a potential molecular mechanism driving the long-term effect of pregnancy on MS outcomes. Our results point to a potential ¿CNS signature¿ of methylation in peripheral immune cells, as previously described in relation to MS progression, induced by parity. As the first epigenome-wide association study of parity in wwMS reported, validation studies are needed to confirm our findings.
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Nova |
2023 |
Xavier A, Maltby VE, Ewing E, Campagna MP, Burnard SM, Tegner JN, et al., 'DNA Methylation Signatures of Multiple Sclerosis Occur Independently of Known Genetic Risk and Are Primarily Attributed to B Cells and Monocytes', International Journal of Molecular Sciences, 24 12576-12576 [C1]
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Nova |
2023 |
Lycett MJ, Lea RA, Maltby VE, Min M, Lechner-Scott J, 'The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis', Multiple Sclerosis Journal - Experimental, Translational and Clinical, 9 (2023) [C1]
Background: Cladribine is a useful therapeutic option in RRMS with moderate to high disease activity. Its oral formulation and tolerability make it a useful alternative to infusio... [more]
Background: Cladribine is a useful therapeutic option in RRMS with moderate to high disease activity. Its oral formulation and tolerability make it a useful alternative to infusion therapies. Cladribine is known to deplete CD19+ B lymphocytes, but its effect on immunoglobulin subsets is unclear. Objective: To identify whether cladribine therapy in pwMS reduces immunoglobulin subset levels as a surrogate marker of infection risk. Methods: A ¿real-world¿ retrospective analysis of 341 pwMS presenting to a single tertiary centre between March 2017 and July 2021. Differences in immunoglobulin levels between cladribine, other disease-modifying therapies and no active treatment were assessed using a univariate ANOVA. Results: Three hundred and forty-one patients had immunoglobulin levels assessed, with 29 patients treated with cladribine. The mean IgG, IgM and IgA levels on cladribine therapy were 10.44 ± 0.40, 0.99 ± 0.09 and 2.04 ± 0.18 g/L respectively. These were not significantly different from patients not on active treatment. There was a statistically significant reduction in IgG and IgM levels for patients treated with ocrelizumab (9.37 ± 0.19 and 0.68 ± 0.04 g/L) and natalizumab (8.72 ± 0.53 and 0.69 ± 0.12 g/L) compared to patients not on treatment. Conclusion: Cladribine therapy for RRMS was not associated with immunoglobulin subset deficiencies. This is contrasted to ocrelizumab and natalizumab which demonstrate significant reductions in both IgG and IgM levels.
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2022 |
Maltby VE, Lea RA, Reeves P, Saugbjerg B, Lechner-Scott J, 'Reduced cognitive function contributes to economic burden of multiple sclerosis', Multiple Sclerosis and Related Disorders, 60 (2022) [C1]
Background: Cognitive impairment is a common symptom of multiple sclerosis (MS). The effect of cognitive impairment in people with MS on employment, quality of life and mental hea... [more]
Background: Cognitive impairment is a common symptom of multiple sclerosis (MS). The effect of cognitive impairment in people with MS on employment, quality of life and mental health is known, however, few studies have investigated if cognitive deficits contribute to the economic burden of MS. Objective: To investigate if cognitive impairment correlates with the economic burden of MS. Methods: The client service receipt inventory was used to determine cost to the healthcare system, participant out of pocket cost, community cost and total societal cost. Quality of life was evaluated using the EuroQoL. Participants cognitive performance was assessed with the Audio Recorded Cognitive Screen and the symbol digit modalities test. Spearman's rank correlation coefficient (r) was used to gauge the strength of the correlation between domain scores and cost metrics. Results: Memory, speed of writing and the symbol digit modalities test were all negatively correlated with all aspects of cost of care (r = 0.24¿0.59, P < 0.5). This was found to be independent of other factors, such as EDSS or mental health indices. Conclusion: Cognitive deficits are independently correlated with the economic burden of MS and should be monitored as part of routine care.
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Nova |
2022 |
Campagna MP, Xavier A, Lea RA, Stankovich J, Maltby VE, Butzkueven H, et al., 'Whole-blood methylation signatures are associated with and accurately classify multiple sclerosis disease severity', Clinical Epigenetics, 14 (2022) [C1]
Background: The variation in multiple sclerosis (MS) disease severity is incompletely explained by genetics, suggesting genetic and environmental interactions are involved. Moreov... [more]
Background: The variation in multiple sclerosis (MS) disease severity is incompletely explained by genetics, suggesting genetic and environmental interactions are involved. Moreover, the lack of prognostic biomarkers makes it difficult for clinicians to optimise care. DNA methylation is one epigenetic mechanism by which gene¿environment interactions can be assessed. Here, we aimed to identify DNA methylation patterns associated with mild and severe relapse-onset MS (RMS) and to test the utility of methylation as a predictive biomarker. Methods: We conducted an epigenome-wide association study between 235 females with mild (n = 119) or severe (n = 116) with RMS. Methylation was measured with the Illumina methylationEPIC array and analysed using logistic regression. To generate hypotheses about the functional consequence of differential methylation, we conducted gene set enrichment analysis using ToppGene. We compared the accuracy of three machine learning models in classifying disease severity: (1) clinical data available at baseline (age at onset and first symptoms) built using elastic net (EN) regression, (2) methylation data using EN regression and (3) a weighted methylation risk score of differentially methylated positions (DMPs) from the main analysis using logistic regression. We used a conservative 70:30 test:train split for classification modelling. A false discovery rate threshold of 0.05 was used to assess statistical significance. Results: Females with mild or severe RMS had 1472 DMPs in whole blood (839 hypermethylated, 633 hypomethylated in the severe group). Differential methylation was enriched in genes related to neuronal cellular compartments and processes, and B-cell receptor signalling. Whole-blood methylation levels at 1708 correlated CpG sites classified disease severity more accurately (machine learning model 2, AUC = 0.91) than clinical data (model 1, AUC = 0.74) or the wMRS (model 3, AUC = 0.77). Of the 1708 selected CpGs, 100 overlapped with DMPs from the main analysis at the gene level. These overlapping genes were enriched in neuron projection and dendrite extension, lending support to our finding that neuronal processes, rather than immune processes, are implicated in disease severity. Conclusion: RMS disease severity is associated with whole-blood methylation at genes related to neuronal structure and function. Moreover, correlated whole-blood methylation patterns can assign disease severity in females with RMS more accurately than clinical data available at diagnosis.
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Nova |
2021 |
Campagna MP, Xavier A, Lechner-Scott J, Maltby V, Scott RJ, Butzkueven H, et al., 'Epigenome-wide association studies: current knowledge, strategies and recommendations', CLINICAL EPIGENETICS, 13 (2021) [C1]
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Nova |
2021 |
Maltby VE, Lea RA, Monif M, Fabis-Pedrini MJ, Buzzard K, Kalincik T, et al., 'Efficacy of Cladribine Tablets as a Treatment for People With Multiple Sclerosis: Protocol for the CLOBAS Study (Cladribine, a Multicenter, Long-term Efficacy and Biomarker Australian Study)', JMIR RESEARCH PROTOCOLS, 10 (2021)
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2020 |
Nguyen AL, Vodehnalova K, Kalincik T, Signori A, Havrdova EK, Lechner-Scott J, et al., 'Association of Pregnancy with the Onset of Clinically Isolated Syndrome', JAMA Neurology, 77 1496-1503 (2020) [C1]
Importance: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode ... [more]
Importance: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS). Objective: To investigate the association of pregnancy with time to CIS onset. Design, Setting, and Participants: This multicenter cohort study collected reproductive history (duration of each pregnancy, date of delivery, length of breastfeeding) on all participants between September 1, 2016, and June 25, 2019. Adult women being treated at the MS outpatient clinics of 4 tertiary hospitals in 2 countries (Charles University and General University Hospital in Prague, Czech Republic; Royal Melbourne Hospital in Melbourne, Australia; Alfred Hospital in Melbourne, Australia; and John Hunter Hospital in Newcastle, Australia) were recruited to participate in the study. Preexisting data (date of CIS onset, date of birth, sex, date of clinical onset, and Expanded Disability Status Scale result) were collected from MSBase, an international registry of long-term prospectively collected data on patients with MS. Data analyses were performed from June 1, 2019, to February 3, 2020. Exposures: Gravida (defined as any pregnancy, including pregnancy that ended in miscarriage and induced abortion) and parity (defined as childbirth after gestational age of more than 20 weeks, including livebirth and stillbirth) before CIS onset. Main Outcomes and Measures: Time to CIS onset. The following were assessed: (1) whether women with previous pregnancies and childbirths had a delayed onset of CIS compared with those who had never been pregnant and those who had never given birth, and (2) whether a dose response existed, whereby a higher number of gravidity and parity was associated with a later onset of CIS. Results: Of the 2557 women included in the study, the mean (SD) age at CIS onset was 31.5 (9.7) years. Of these women, before CIS onset, 1188 (46%) had at least 1 pregnancy and 1100 (43%) had at least 1 childbirth. The mean (SD) age at first pregnancy was 23.3 (4.5) years and at first childbirth was 23.8 (4.5) years. Women with previous pregnancies and childbirths had a later onset of CIS compared with those who had never been pregnant (HR, 0.68; 95% CI, 0.62-0.75; P <.001), with a median delay of 3.3 (95% CI, 2.5-4.1) years. Women who had given birth also had a later CIS onset compared with women who had never given birth (HR 0.68; 95% CI, 0.61-0.75; P <.001), with a similar median delay of 3.4 (95% CI, 1.6-5.2) years. A higher gravidity and parity number was not associated with delay in CIS onset. Conclusions and Relevance: This study suggests an association between previous pregnancies and childbirths and timing of CIS onset, but having more pregnancies or childbirths did not appear to be associated with a later CIS onset. Further studies are needed to help explain the mechanisms behind the associations between pregnancy and onset of multiple sclerosis 2020 American Medical Association. All rights reserved.
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Nova |
2020 |
Groen K, Maltby VE, Scott RJ, Tajouri L, Lechner-Scott J, 'Erythrocyte microRNAs show biomarker potential and implicate multiple sclerosis susceptibility genes.', Clinical and translational medicine, 10 74-90 (2020) [C1]
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Nova |
2020 |
Maltby VE, Lea RA, Burnard S, Xavier A, Van Cao T, White N, et al., 'Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients', SCIENTIFIC REPORTS, 10 (2020) [C1]
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Nova |
2020 |
Lechner-Scott J, Hawkes CH, Giovannoni G, Levy M, Maltby V, 'Why should Neurologists get involved in family planning?', MULTIPLE SCLEROSIS AND RELATED DISORDERS, 46 (2020)
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2020 |
Groen K, Maltby VE, Scott RJ, Tajouri L, Lechner-Scott J, 'Concentrations of plasma-borne extracellular particles differ between multiple sclerosis disease courses and compared to healthy controls', Multiple Sclerosis and Related Disorders, 45 (2020) [C1]
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Nova |
2020 |
Maltby VE, Lea RA, Ribbons K, Lea MG, Schofield PW, Lechner-Scott J, 'Comparison of BICAMS and ARCS for assessment of cognition in multiple sclerosis and predictive value of employment status', Multiple Sclerosis and Related Disorders, 41 (2020) [C1]
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Nova |
2018 |
Groen K, Lea RA, Maltby VE, Scott RJ, Lechner-Scott J, 'Letter to the editor: blood processing and sample storage have negligible effects on methylation', CLINICAL EPIGENETICS, 10 (2018) [C1]
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Nova |
2018 |
Maltby VE, Lea RA, Graves MC, Sanders KA, Benton MC, Tajouri L, et al., 'Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients.', Scientific reports, 8 (2018) [C1]
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Nova |
2018 |
Rhead B, Brorson IS, Berge T, Adams C, Quach H, Moen SM, et al., 'Increased DNA methylation of SLFN12 in CD4(+) and CD8(+) T cells from multiple sclerosis patients', PLOS ONE, 13 (2018) [C1]
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Nova |
2018 |
Groen K, Maltby VE, Lea RA, Sanders KA, Fink JL, Scott RJ, et al., 'Erythrocyte microRNA sequencing reveals differential expression in relapsing-remitting multiple sclerosis.', BMC medical genomics, 11 (2018) [C1]
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Nova |
2018 |
Maltby VE, Lea RA, Ribbons KA, Sanders KA, Kennedy D, Min M, et al., 'DNA methylation changes in CD4+ T cells isolated from multiple sclerosis patients on dimethyl fumarate.', Multiple Sclerosis Journal - Experimental, Translational and Clinical, 4 (2018) [C1]
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Nova |
2017 |
Martin BJE, McBurney KL, Maltby VE, Jensen KN, Brind Amour J, Howe LAJ, 'Histone H3K4 and H3K36 methylation independently recruit the NuA3 histone acetyltransferase in Saccharomyces cerevisiae', Genetics, 205 1113-1123 (2017) [C1]
Histone post-translational modifications (PTMs) alter chromatin structure by promoting the interaction of chromatinmodifying complexes with nucleosomes. The majority of chromatin-... [more]
Histone post-translational modifications (PTMs) alter chromatin structure by promoting the interaction of chromatinmodifying complexes with nucleosomes. The majority of chromatin-modifying complexes contain multiple domains that preferentially interact with modified histones, leading to speculation that these domains function in concert to target nucleosomes with distinct combinations of histone PTMs. In Saccharomyces cerevisiae, the NuA3 histone acetyltransferase complex contains three domains, the PHD finger in Yng1, the PWWP domain in Pdp3, and the YEATS domain in Taf14; which in vitro bind to H3K4 methylation, H3K36 methylation, and acetylated and crotonylated H3K9, respectively. While the in vitro binding has been well characterized, the relative in vivo contributions of these histone PTMs in targeting NuA3 is unknown. Here, through genome-wide colocalization and by mutational interrogation, we demonstrate that the PHD finger of Yng1, and the PWWP domain of Pdp3 independently target NuA3 to H3K4 and H3K36 methylated chromatin, respectively. In contrast, we find no evidence to support the YEATS domain of Taf14 functioning in NuA3 recruitment. Collectively our results suggest that the presence of multiple histone PTM binding domains within NuA3, rather than restricting it to nucleosomes containing distinct combinations of histone PTMs, can serve to increase the range of nucleosomes bound by the complex. Interestingly, however, the simple presence of NuA3 is insufficient to ensure acetylation of the associated nucleosomes, suggesting a secondary level of acetylation regulation that does not involve control of HAT-nucleosome interactions.
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Nova |
2017 |
Maltby VE, Lea RA, Sanders KA, White N, Benton MC, Scott RJ, Lechner-Scott J, 'Differential methylation at MHC in CD4
Background: Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains uncertainty as to how... [more]
Background: Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains uncertainty as to how these variants contribute to disease. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. In a previous study, we found a differentially methylation region (DMR) at MHC HLA-DRB1 that was associated within relapsing-remitting MS (RRMS) patients in CD4+ T cells. This study aimed to confirm this earlier finding in an independent RRMS cohort of treatment-naive female patients. Methods: Total genomic DNA was extracted from CD4+ T cells of 28 female RRMS and 22 age-matched healthy controls subjects. DNA was bisulfite-converted and hybridised to Illumina 450K arrays. Beta values for all CpGs were analysed using the DMPFinder function in the MINFI program, and a follow-up prioritisation process was applied to identify the most robust MS-associated DMRs. Results: This study confirmed our previous findings of a hypomethylated DMR at HLA-DRB1 and a hypermethylated DMR at HLA-DRB5 in this RRMS patient cohort. In addition, we identified a large independent DMR at MHC, whereby 11 CpGs in RNF39 were hypermethylated in MS cases compared to controls (max. ¿beta = 0.19, P = 2.1 × 10-4). We did not find evidence that SNP genotype was influencing the DMR in this cohort. A smaller MHC DMR was also identified at HCG4B, and two non-MHC DMRs at PM20D1 on chr1 and ERICH1 on chr8 were also identified. Conclusions: The findings from this study confirm our previous results of a DMR at HLA-DRB1 and also suggest hypermethylation in an independent MHC locus, RNF39, is associated with MS. Taken together, our results highlight the importance of epigenetic factors at the MHC locus in MS independent of treatment, age and sex. Prospective studies are now required to discern whether methylation at MHC is involved in influencing risk of disease onset or whether the disease itself has altered the methylation profile.
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Nova |
2016 |
Sanders KA, Benton MC, Lea RA, Maltby VE, Agland S, Griffin N, et al., 'Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+T cells', CLINICAL EPIGENETICS, 8 (2016) [C1]
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Nova |
2016 |
Groen K, Maltby VE, Sanders KA, Scott RJ, Tajouri L, Lechner-Scott J, 'Erythrocytes in multiple sclerosis - forgotten contributors to the pathophysiology?', Multiple Sclerosis Journal Experimental, Translational and Clinical, 2 2055217316649981-2055217316649981 (2016) [C1]
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Nova |
2016 |
Murray HC, Maltby VE, Smith DW, Bowden NA, 'Nucleotide excision repair deficiency in melanoma in response to UVA', Experimental Hematology and Oncology, 5 (2016) [C1]
Background: The causative link between UV exposure and melanoma development is well known, however the mechanistic relationship remains incompletely characterised. UVA and UVB com... [more]
Background: The causative link between UV exposure and melanoma development is well known, however the mechanistic relationship remains incompletely characterised. UVA and UVB components of sunlight are implicated in melanomagenesis; however the majority of studies have focused on the effects of UVB and UVC light. Interestingly, melanoma tumour sequencing has revealed an overrepresentation of mutations signature of unrepaired UV-induced DNA damage. Repair of UVA-induced DNA damage is thought to occur primarily through the Nucleotide Excision Repair (NER) pathway, which recognises and repairs damage either coupled to transcription (Transcription Coupled Repair; TCR), or through global genome scanning (Global Genome Repair; GGR). Current literature suggests NER is deficient in melanoma, however the cause of this remains unknown; and whether reduced NER activity in response to UVA may be involved in melanoma development remains uncharacterised. In this study we aimed to determine if melanoma cells exhibit reduced levels of NER activity in response to UVA. Methods: Melanocyte and melanoma cell lines were UVA-irradiated, and DNA damage levels assessed by immunodetection of Cyclobutane Pyrimidine Dimer (CPD) and (6-4) Photoproduct [(6-4)PP] lesions. Expression of NER pathway components and p53 following UVA treatment was quantified by qPCR and western blot. Results: UVA did not induce detectable induction of (6-4)PP lesions, consistent with previous studies. Repair of CPDs induced by UVA was initiated at 4 h and complete within 48 h in normal melanocytes, whereas repair initiation was delayed to 24 h and >40 % of lesions remained in melanoma cell lines at 48 h. This was coupled with a delayed and reduced induction of GGR component XPC in melanoma cells, independent of p53. Conclusion: These findings support that NER activity is reduced in melanoma cells due to deficient GGR. Further investigation into the role of NER in UVA-induced melanomagenesis is warranted and may have implications for melanoma treatment.
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Nova |
2015 |
Maltby VE, Graves MC, Lea RA, Benton MC, Sanders KA, Tajouri L, et al., 'Genome-wide DNA methylation profiling of CD8+T cells shows a distinct epigenetic signature to CD4+T cells in multiple sclerosis patients', CLINICAL EPIGENETICS, 7 (2015) [C1]
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Nova |
2014 |
Maltby VE, Crock PA, Luedecke DK, 'A rare case of pituitary infarction leading to spontaneous tumour resolution and CSF-sella syndrome in an 11-year-old girl and a review of the paediatric literature', JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, 27 939-946 (2014) [C3]
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Nova |
2014 |
Smith CJA, Bensing S, Maltby VE, Zhang M, Scott RJ, Smith R, et al., 'Intermediate lobe immunoreactivity in a patient with suspected lymphocytic hypophysitis', Pituitary, 17 22-29 (2014) [C1]
Lymphocytic hypophysitis is an organ-specific autoimmune disease characterised by destruction of pituitary hormone-secreting cells due to attack by self-reactive T lymphocytes. Th... [more]
Lymphocytic hypophysitis is an organ-specific autoimmune disease characterised by destruction of pituitary hormone-secreting cells due to attack by self-reactive T lymphocytes. The spectrum of pituitary autoantibodies characterised by indirect immunofluorescence (IF) in these patients has not been substantially defined. The purpose of this study was to determine the spectrum of pituitary autoantibodies in 16 lymphocytic hypophysitis patients. Pituitary sections were prepared from guinea pigs and sera from 16 lymphocytic hypophysitis patients (13 biopsy proven and 3 suspected cases) and 13 healthy controls were evaluated for immunoreactivity to the pituitary tissue by immunofluorescence. A single patient was found to have high titre pituitary autoantibodies against guinea pig pituitary tissue. Immunoreactivity was directed against cells of the intermediate lobe. We present the case report of the patient who is a 24 year old woman that presented with headaches, polyuria and polydipsia. A uniformly enlarged pituitary mass was visible on MRI and a diagnosis of suspected lymphocytic hypophysitis was made. Based on our IF study, we postulate this patient has an autoimmune process directed towards the major cell type in the intermediate lobe, the melanotroph. Pre-adsorption with peptides representing adrenocorticotropic hormone, a-melanocyte stimulating hormone or ß-endorphin did not affect the IF signal suggesting our patient's pituitary autoantibodies may target some other product of Proopiomelanocortin (POMC) processing, such as corticotrophin-like intermediate peptide or ¿-lipoprotein. Alternatively, the autoantibodies may target a peptide completely unrelated to POMC processing. © 2013 Springer Science+Business Media New York.
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2012 |
Maltby VE, Martin BJ, Brind'Amour J, Chruscicki AT, McBurney KL, Schulze JM, et al., 'Histone H3K4 demethylation is negatively regulated by histone H3 acetylation in Saccharomyces cerevisiae', Proceedings of the National Academy of Sciences of USA, 109 8505-8510 (2012) [C1]
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2012 |
Maltby VE, Martin BJ, Schulze JM, Johnson IJ, Hentrich T, Sharma A, et al., 'Histone H3 lysine 36 methylation targets the Isw1b remodeling complex to chromatin', Molecular and Cellular Biology, 32 3479-3485 (2012) [C1]
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2010 |
Chruscicki AT, MacDonald VE, Young BP, Loewen CJ, Howe LJ, 'Critical Determinants for Chromatin Binding by Saccharomyces cerevisiae Yng1 Exist Outside of the Plant Homeodomain Finger', Genetics, 185 469-477 (2010) [C1]
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2009 |
MacDonald VE, Howe LJ, 'Histone acetylation: where to go and how to get there.', Epigenetics, 4 139-143 (2009) [C2]
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2006 |
Martin DG, Baetz K, Shi X, Walter K, MacDonald VE, Wlodarski MJ, et al., 'The Yng1p plant homeodomain finger is a methyl-histone binding module that recognizes lysine 4-methylated histone H3.', Molecular and Cellular Biology, 26 7871-7879 (2006) [C1]
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