A5054339123- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Prostate Cancer Treatment and Research
- Renal and related cancers
- Acute Lymphoblastic Leukemia research
- Cell Adhesion Molecules Research
- FOXO transcription factor regulation
- PARP inhibition in cancer therapy
- Viral Infectious Diseases and Gene Expression in Insects
- Tissue Engineering and Regenerative Medicine
- Protease and Inhibitor Mechanisms
- Advanced Breast Cancer Therapies
- CAR-T cell therapy research
- RNA regulation and disease
- Cancer-related Molecular Pathways
- Sirtuins and Resveratrol in Medicine
- Cancer Genomics and Diagnostics
- Multiple Myeloma Research and Treatments
- Genomics, phytochemicals, and oxidative stress
- Cancer-related molecular mechanisms research
- Pluripotent Stem Cells Research
- Chronic Myeloid Leukemia Treatments
University of Birmingham
2017-2024
University of Tasmania
2011-2015
Abstract Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option still chemotherapy targets such However, patients harbour quiescent leukemic stem cells (LSCs) can emerge from quiescence trigger...
Highlights•An RNAi screen identifies CCND2 as a crucial transcriptional target of RUNX1/ETO•RUNX1/ETO promotes expression by binding to an upstream element•CCND2 knockdown inhibits RUNX1/ETO-driven leukemic expansion in vitro and vivo•RUNX1/ETO-expressing cells are highly sensitive CDK4/6 inhibitorSummaryOncogenic transcription factors such the fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but challenging therapeutic targets. We used...
The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukemia. Relapse can be associated with lineage switch from to myeloid leukemia, resulting in poor clinical outcomes caused by resistance chemotherapies and immunotherapies. In this study, the relapses shared oncogene breakpoints their matched lymphoid presentations originated various differentiation stages immature progenitors through committed B-cell precursors. Lineage switching is linked substantial changes...
Acute myeloid leukemia (AML) is associated with mutations in transcriptional and epigenetic regulator genes impairing differentiation. The t(8;21)(q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes hematopoietic master RUNX1. We previously showed that maintenance of t(8;21) AML dependent on expression. Its depletion causes extensive changes transcription factor binding, as well gene expression, initiates However, how these processes are connected within a...
Prostate cancer is a commonly diagnosed in men and leading cause of deaths. Whilst the underlying mechanisms to prostate are still be determined, it evident that both genetic epigenetic changes contribute development progression this disease. Epigenetic involving DNA hypo- hypermethylation, altered histone modifications more recently microRNA expression have been detected at range genes associated with cancer. Furthermore, there evidence particular different stages early detection can lead...
BACKGROUND Integrin alpha2 beta1 (α 2 β 1 ) plays an integral role in tumour cell invasion, metastasis and angiogenesis, altered expression of the receptor has been linked to prognosis several solid tumours. However, relationship is complex, with both increased decreased associated different stages metastases types. The ITGA2 gene, which codes for α subunit, was examined investigate whether a large CpG island its promoter region involved differential observed prostate cancer. METHODS...
Acute myeloid leukemia (AML) is a heterogeneous disease caused by different mutations. Previously, we showed that each mutational subtype develops its specific gene regulatory network (GRN) with transcription factors interacting within multiple modules, many of which are factor genes themselves. Here, hypothesize highly connected nodes such networks comprise crucial regulators AML maintenance. We test this hypothesis using FLT3-ITD-mutated as model and conduct an shRNA drop-out screen...
Abstract Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by mutations in genes encoding transcriptional and epigenetic regulators together with signaling genes. It characterized disturbance of differentiation abnormal proliferation hematopoietic progenitors. We have previously shown that each AML subtype establishes its own core gene regulatory network (GRN), consisting transcription factors binding to their target imposing specific expression pattern required...
Key Points C/EBPα directly represses the leukemia maintenance program; however, pattern of repressed genes is specific for each type AML. Overexpression does not globally displace these proteins from their binding sites, but overrides repressive activity.
The role of fibroblasts in determining tissue topography and immune cell organisation within chronically inflamed tissues is poorly understood. Herein, we use multi-omic spatial analysis to define the cellular zonation pattern synovium patients with inflammatory arthritis, identifying discrete niches underpinned by spatially programmed subsets synovial fibroblasts. We observe that perivascular switch on distinct matrix programs response cytokine signalling from neighbouring cells, forming...
AML is a heterogenous disease caused by different mutations. We have previously shown that each mutational sub-type develops its specific gene regulatory network (GRN) with transcription factors interacting multiple modules, many of which are factor genes themselves. Here we hypothesized highly connected nodes within such networks comprise crucial regulators maintenance. tested this hypothesis using FLT3-ITD mutated as model and conducted an shRNA drop-out screen informed analysis. show...
Summary Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option still chemotherapy targets such However, patients harbour quiescent leukemic stem cells (LSCs) can emerge from quiescence trigger...