A5102946135- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- MicroRNA in disease regulation
- Chronic Myeloid Leukemia Treatments
- Bone Metabolism and Diseases
- Cancer-related molecular mechanisms research
- Genetics and Neurodevelopmental Disorders
- Immune Cell Function and Interaction
- Gene expression and cancer classification
- Immune Response and Inflammation
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Neuroblastoma Research and Treatments
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Immunodeficiency and Autoimmune Disorders
- NF-κB Signaling Pathways
- Neuroendocrine regulation and behavior
- Cancer Cells and Metastasis
- Molecular Biology Techniques and Applications
Walter and Eliza Hall Institute of Medical Research
2012-2024
The University of Melbourne
2011-2024
Ningbo Medical Center Lihuili Hospital
2024
Ningbo University
2024
Kuang Tien General Hospital
2020
The Netherlands Cancer Institute
2012
Oncode Institute
2012
limma is an R/Bioconductor software package that provides integrated solution for analysing data from gene expression experiments. It contains rich features handling complex experimental designs and information borrowing to overcome the problem of small sample sizes. Over past decade, has been a popular choice discovery through differential analyses microarray high-throughput PCR data. The particularly strong facilities reading, normalizing exploring such Recently, capabilities have...
Hematopoiesis is a multistage process involving the differentiation of stem and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, an atlas murine gene-expression data containing 54 hematopoietic types, covering all lineages in hematopoiesis. We include rare populations such as eosinophils, mast cells, basophils, megakaryocytes, broad collection cells. show that lineage branching maturation during hematopoiesis can be reconstructed using expression patterns...
During immune responses, neutrophils must integrate survival and death signals from multiple sources to regulate their lifespan. Signals that activate either the Bcl-2- or receptor-regulated apoptosis pathways can provide powerful stimuli for undergo cell death, but whether they act cooperatively in parallel directly cross-talk is not known. Previous studies suggested Bcl-2 family proteins are required Fas-induced neutrophils, did examine could modulate its rapid onset. By monitoring rate of...
Loss-of-function mutations in hematopoietic transcription factors including PAX5 occur most cases of B-progenitor acute lymphoblastic leukemia (B-ALL), a disease characterized by the accumulation undifferentiated lymphoblasts. Although mutation is critical driver B-ALL development mice and humans, it remains unclear how its loss contributes to leukemogenesis whether ongoing deficiency required for maintenance. Here we used transgenic RNAi reversibly suppress endogenous Pax5 expression...
Abstract The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role adaptive unclear. Here we show that the LUBAC components HOIP, HOIL-1 SHARPIN have roles late thymocyte differentiation, FOXP3 + regulatory T (Treg)-cell development Treg cell homeostasis. activity not required to prevent TNF-induced apoptosis or necroptosis but necessary transcriptional programme of penultimate stage differentiation. cell-specific ablation HOIP...
Abstract Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until remodeled. The interconnected osteocyte network within the matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. not caused by low...
In the conventional model of transcriptional activation, transcription factors bind to response elements and recruit co-factors, including histone acetyltransferases. Contrary this model, we show that acetyltransferase KAT7 (HBO1/MYST2) is required genome wide for H3 lysine 14 acetylation (H3K14ac). Examining neural stem cells, find H3K14ac are present not only at transcribed genes but also inactive genes, intergenic regions, in heterochromatin. were continued actively time loss...
Recent studies have established that mutations or deletions in microRNA (miRNA) processing enzymes resulting a global decrease of miRNA expression are frequent across cancers and can be associated with poorer prognosis. While very popular profiling studies, it remains unclear whether microarrays suited not to accurately detecting decreases seen cancers. In this work, we analyzed the profiles samples using Affymetrix following inducible genetic deletion Dicer1 . Surprisingly, up third...
Neural tube defects (NTDs) are common birth in humans and show an unexplained female bias. Female mice lacking the tumor suppressor p53 display NTDs with incomplete penetrance. We found that combined loss of pro-apoptotic BIM caused 100% penetrant, female-exclusive NTDs, which allowed us to investigate female-specific functions p53. report p53-/- embryonic neural samples fewer cells inactive X chromosome markers Xist H3K27me3 a concomitant increase biallelic expression X-linked genes, Huwe1...
Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins molecular processes that contribute to SqCC formation are largely unexplored. Here we show human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor counterparts have limited colony-forming capacity. We demonstrate this difference arises in part because...
Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are IL-6 family members with a wide range of biological functions. Human OSM (hOSM) murine LIF (mLIF) act in mouse cells via receptor (LIFR)-glycoprotein 130 (gp130) heterodimer. In contrast, (mOSM) signals mainly an (OSMR)-gp130 heterodimer binds only very low affinity to mLIFR. hOSM mLIF stimulate bone remodeling by both reducing osteocytic sclerostin up-regulating the pro-osteoclastic activator NF-κB ligand (RANKL) osteoblasts....
Heterozygous mutations in the histone lysine acetyltransferase gene KAT6B ( MYST4/MORF/QKF ) underlie neurodevelopmental disorders, but mechanistic roles of remain poorly understood. Here, we show that loss embryonic neural stem and progenitor cells (NSPCs) impaired cell proliferation, neuronal differentiation, neurite outgrowth. Mechanistically, resulted reduced acetylation at H3 9 expression key nervous system development genes NSPCs developing cortex, including SOX family, particular Sox2...
Abstract SMCHD1 is an epigenetic modifier of gene expression that critical to maintain X chromosome inactivation. Here, we show in mouse genetic inactivation Smchd1 accelerates tumorigenesis male mice. Loss transformed embryonic fibroblasts increased tumor growth upon transplantation into immunodeficient nude In addition, loss Eμ-Myc transgenic mice undergo lymphomagenesis reduced disease latency by 50% relative control animals. premalignant deficient Smchd1, there was increase the number...
MicroRNAs (miRNAs) have been implicated in governing lineage specification and differentiation multiple organs; however, little is known about their specific roles mammopoiesis. We determined the global miRNA expression profiles of functionally distinct epithelial subpopulations mouse human mammary tissue, compared these to cognate transcriptomes epigenomes. Finally, signatures were used interrogate different subtypes breast cancer, with a view determining networks deregulated during...
Genetic alterations disrupting the transcription factor IKZF1 (encoding IKAROS) are associated with poor outcome in B lineage acute lymphoblastic leukemia (B-ALL) and occur >70% of high-risk BCR-ABL1+ (Ph+) Ph-like disease subtypes. To examine IKAROS function this context, we have developed novel mouse models allowing reversible RNAi-based control Ikaros expression established B-ALL vivo. Notably, leukemias driven by combined BCR-ABL1 suppression rapidly regress when endogenous is...
Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human aneuploidy. Pre-leukemic myeloproliferative changes in DS foetal livers precede acquisition GATA1 mutations, transient disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy Erg gene required for myeloproliferation Ts(1716)65Dn mouse model. We demonstrate here that genetic specifically attributable to lead lineage priming primitive early multipotential progenitor cells mice, excess...