Rhys S. Allan
A5003796244- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Immune cells in cancer
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Chromosomal and Genetic Variations
- Nuclear Structure and Function
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Histone Deacetylase Inhibitors Research
- CAR-T cell therapy research
- NF-κB Signaling Pathways
- Telomeres, Telomerase, and Senescence
- Protein Degradation and Inhibitors
- vaccines and immunoinformatics approaches
- Cancer-related molecular mechanisms research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA Research and Splicing
- Acute Myeloid Leukemia Research
- Immune responses and vaccinations
Walter and Eliza Hall Institute of Medical Research
2016-2025
The University of Melbourne
2016-2025
Institut Curie
2012
Inserm
2012
The classical paradigm for dendritic cell function derives from the study of Langerhans cells, which predominate within skin epidermis. After an encounter with foreign agents, cells are thought to migrate draining lymph nodes, where they initiate T priming. Contrary this, we show here that infection murine epidermis by herpes simplex virus did not result in priming virus-specific cytotoxic lymphocytes cells. Rather, response required a distinct CD8alpha+ subset. Thus, traditional view...
Abstract Neutrophils are implicated in multiple homeostatic and pathological processes, but whether functional diversity requires discrete neutrophil subsets is not known. Here, we apply single-cell RNA sequencing to neutrophils from normal inflamed mouse tissues. Whereas conventional clustering yields alternative organizational structures, diffusion mapping plus velocity discloses a single developmental spectrum, ordered chronologically. Termed here neutrotime, this spectrum extends...
Abstract Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it unknown whether stable non-genetic can be overcome. Using single cell RNA-sequencing of paired naïve resistant AML patient samples cellular barcoding a unique mouse model resistance, here we demonstrate that transcriptional plasticity drives epigenetic resistance. With CRISPR-Cas9 screen identify regulators enhancer function as important modulators the...
To separate causal effects of histone acetylation on chromatin accessibility and transcriptional output, we used integrated epigenomic transcriptomic analyses following acute inhibition major cellular lysine acetyltransferases P300 CBP in hematological malignancies. We found that catalytic P300/CBP dynamically perturbs steady-state kinetics suppresses oncogenic networks the absence changes to accessibility. CRISPR-Cas9 screening identified NCOR1 HDAC3 co-repressors as principal antagonists...
Inflammatory cytokines are fundamental mediators of the organismal response to injury, infection, or other harmful stimuli. To elucidate early and mostly direct transcriptional signatures inflammatory cytokines, we profiled all immunologic cell types by RNAseq after systemic exposure IL1β, IL6, TNFα. Our results revealed a significant overlap in responses, with broad divergence between myeloid lymphoid cells, but very few cell-type-specific responses. Pathway motif analysis identified...
Abstract Skin-draining lymph nodes contain a number of dendritic cell (DC) subsets different origins. Some these are migratory, such as the skin-derived epidermal Langerhans cells and separate dermal DC subset, whereas others lymphoid resident in nature, CD8+ DCs found throughout tissues. In this study, we examine subset presentation self-Ag by migratory lymphoid-resident DCs, both steady state under conditions local skin infection. We show that is confined to migrating settings. Steady...
Abstract Remodelling of chromatin architecture is known to regulate gene expression and has been well characterized in cell lineage development but less so response perturbation. Activation T cells, which triggers extensive changes transcriptional programs, serves as an instructive model elucidate how orchestrate To characterize coordinate at different levels architecture, we analyzed accessibility, chromosome conformation activated human cells. activation was by widespread accessibility...
H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes differentiation development. Here, we investigate molecular consequences loss cells deficient both SUV39H1 SUV39H2 (Suv39DKO), major mammalian histone methyltransferase enzymes that catalyze heterochromatic H3K9me3 deposition. We reveal a paradoxical repression Suv39DKO cells, with these differentially expressed...
Dendritic cells (DCs) are extremely heterogeneous, most evident in the skin where a variety of different subsets have been identified recent years. DCs healthy include number distinct populations dermal layer as well well-characterized Langerhans (LCs) epidermis. These steady-state augmented during bouts local inflammation by additional monocyte-derived DCs. In an effort to better understand distinction between subsets, we examined their behavior following infection with HSV. LC emigration...
Abstract B lymphoid development is initiated by the differentiation of hematopoietic stem cells into lineage committed progenitors, ultimately generating mature cells. This highly regulated process generates clonal immunological diversity via recombination immunoglobulin V, D and J gene segments. While several transcription factors that control cell V(D)J have been defined, how these processes are coordinated a precise regulatory network remains poorly understood. Here, we show factor ETS...
During cellular differentiation chromosome conformation is intricately remodelled to support the lineage-specific transcriptional programs required for initiating and maintaining lineage identity. When these changes occur in relation cell cycle, division time response activation signals has yet be explored, although it been proposed during DNA synthesis or after mitosis. Here, we elucidate conformational B lymphocytes as they differentiate expand from a naive, quiescent state into antibody...
It has been proposed that interactions between mammalian chromosomes, or transchromosomal (also known as kissing chromosomes), regulate gene expression and cell fate determination. Here we aimed to identify novel in immune cells by high-resolution genome-wide chromosome conformation capture. Although readily identified stable cis, also centromeres telomeres on different surprisingly no regulatory either mouse human cells, including previously described interactions. We suggest advances the...