A5046391142- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Immune responses and vaccinations
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Multiple Sclerosis Research Studies
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Family Support in Illness
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Cancer, Lipids, and Metabolism
- Renal and related cancers
- Reproductive System and Pregnancy
- Hematopoietic Stem Cell Transplantation
- Protein Degradation and Inhibitors
- Viral-associated cancers and disorders
- Polyomavirus and related diseases
- Genetic Associations and Epidemiology
- Immune cells in cancer
Hunter Medical Research Institute
2017-2025
University of Newcastle Australia
2018-2025
Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) myelodysplastic syndrome. HMAs act in a replication-dependent manner remove DNA methylation from the genome. However, AML cells targeted by HMA therapy often quiescent within bone marrow, where oxygen levels low. In this study, we investigate effects of hypoxia on responses cells. cell lines (MOLM-13, MV-4-11, HL-60) were...
Objective: To understand the immediate impact that testicular heat stress has on isolated populations of precursor male germ cells including Spermatocytes and Spermatids. Design: Mice were given pre-cursor immediately isolated. RNA sequencing was performed validated using qPCR. Subjects: This work carried out in adult CD1 mice. Results: Using next-generation 134 differentially expressed transcripts found to be upon exposure hyperthermia, 93% which upregulated. In addition, hyperthermia...
DNA methylation is an epigenetic mark that influenced by environmental factors and associated with changes to gene expression phenotypes. It may link exposures disease etiology or indicate important pathways involved in pathogenesis. We identified genomic regions are differentially methylated T cells of patients relapsing remitting multiple sclerosis (MS) compared healthy controls. was assessed at 450,000 sites CD4+ CD8+ purified from peripheral blood 94 women MS women, were using...
Epigenetic mechanisms can regulate how DNA is expressed independently of sequence and are known to be associated with various diseases. Among those epigenetic mechanisms, methylation (DNAm) influenced by genotype the environment, making it an important molecular interface for studying disease etiology progression. In this study, we examined whole blood profiles a large group people (pw) multiple sclerosis (MS) compared controls. We reveal that differences in pwMS occur genetic risk loci show...
Global changes in DNA methylation are observed development and disease, single-cell analyses highlighting the heterogeneous regulation of these processes. However, technical challenges associated with analysis limit studies. We present transposable element sequencing (scTEM-seq) for cost-effective estimation average levels. By targeting high-copy SINE Alu elements, we achieve amplicon bisulphite thousands loci covered each scTEM-seq library. Parallel transcriptome is also performed to link...
The pathology of progressive multiple sclerosis (MS) is poorly understood. We have previously assessed DNA methylation in the CD4+ T cells relapsing-remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) HLA-DRB1 RNF39. This study aimed investigate profiles patients. was measured two separate case/control cohorts using Illumina 450K/EPIC arrays data analysed with Chip Analysis Methylation Pipeline (ChAMP). Single nucleotide...
DNA hypomethylating agents (HMAs) are used to treat acute myeloid leukaemia (AML) and myelodysplasia patients who unsuitable for intensive chemotherapy, but low response rates therapy-resistant relapse remain significant challenges. To optimise HMA efficacy, we must understand how resistance arise from cells that survive treatment. Here combine single-cell multi-omic analysis with parallel colony-forming assays link HMA-induced molecular heterogeneity functional consequences in AML cells....
Abstract Multiple sclerosis is a complex autoimmune disease that causes neuronal demyelination and debilitating physical cognitive symptoms. Epigenetic factors can mediate genetic environmental effects on risk. Here we profiled blood-based DNA methylation in 583 MS cases 643 healthy controls representing 3 independent study groups. An epigenome-wide association was performed, incorporating statistical deconvolution to identify immune cell-specific signals, which were validated purified cell...
Conventional genome-wide association studies (GWASs) of complex traits, such as Multiple Sclerosis (MS), are reliant on per-SNP p-values and therefore heavily burdened by multiple testing correction. Thus, in order to detect more subtle alterations, ever increasing sample sizes required, while ignoring potentially valuable information that is readily available existing datasets. To overcome this, we used penalised regression incorporating elastic net with a stability selection method...
Abstract Background Acute myeloid leukaemia (AML) is a deadly haematological malignancy that originates from mutated progenitor cells lie quiescent in the hypoxic bone marrow. Elderly patients who cannot tolerate standard chemotherapies are administered low-dose hypomethylating agents (HMA) which act replication-dependent manner to reprogram epigenome. Relapse common following HMA treatment and may arise Therefore, effects of hypoxia on efficacy influence AML progression. Results cell lines...
Abstract Many powerful techniques are available for the analysis of single cell DNA methylation, but all have associated technical challenges. Throughput and coverage common challenges, expense is a limitation practically methylation related multiomic methods. Single transposable element sequencing (scTEM-seq) provides simplified protocol global that alleviates costs with sequencing. Paired fluorescence activated sorting (FACS) parallel transcriptome each cell, scTEM-seq allows effects...
ABSTRACT Global changes in DNA methylation are observed developmental and disease contexts, singlecell analyses highlighting the heterogeneous regulation of these processes. However, technical challenges associated with single-cell analysis limit studies. We present transposable element sequencing (scTEM-seq) for cost-effective estimation global levels. By targeting high-copy LINE-1 SINE Alu elements, we achieve amplicon bisulphite thousands loci covered each library. Parallel transcriptome...