A5051416931- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Hepatitis B Virus Studies
- Immunotherapy and Immune Responses
- Cell death mechanisms and regulation
- interferon and immune responses
- CAR-T cell therapy research
- Hepatitis C virus research
- Inflammasome and immune disorders
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Phagocytosis and Immune Regulation
- Tuberculosis Research and Epidemiology
- Liver Disease Diagnosis and Treatment
- RNA regulation and disease
- Platelet Disorders and Treatments
- Kruppel-like factors research
- Melanoma and MAPK Pathways
- Proteoglycans and glycosaminoglycans research
- Autoimmune and Inflammatory Disorders Research
- Respiratory viral infections research
- Hepatitis Viruses Studies and Epidemiology
Walter and Eliza Hall Institute of Medical Research
2013-2023
The University of Melbourne
2012-2023
King's College Hospital
2006
King University
2006
Universitat de Barcelona
2006
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2006
Medizinische Hochschule Hannover
2006
German Primate Center
2006
Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm up-regulate CD69 and down-regulate molecules associated with egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in and, together related Blimp1, mediates development skin, gut, liver, kidney mice. The...
Naturally acquired immunity to malaria develops only after years of repeated exposure Plasmodium parasites. Despite the key role antibodies play in protection, cellular processes underlying slow acquisition remain unknown. Using mouse models, we show that severe infection inhibits establishment germinal centers (GCs) spleen. We demonstrate induces high frequencies T follicular helper (Tfh) cell precursors but results impaired Tfh differentiation. expression Bcl-6 and IL-21, precursor cells...
Significance Current antiviral treatments for chronic hepatitis B virus (HBV) infection are effective in suppressing production of virus, but they have poor efficacy promoting the elimination infection. Hence, most patients with HBV maintained on therapies indefinitely. There is much interest identifying that promote clearance infected hepatocytes, thus purging DNA reservoir liver. Here, we show clinical-stage drug birinapant, which antagonizes host cell inhibitor apoptosis proteins (cIAPs),...
Hepatitis B virus (HBV) infection can result in a spectrum of outcomes from immune-mediated control to disease progression, cirrhosis, and liver cancer. The host molecular pathways that influence contribute these need be defined. Using an immunocompetent mouse model chronic HBV infection, we identified some the cellular factors impact on outcomes. Here, show inhibitor apoptosis proteins (cIAPs) attenuate TNF signaling during hepatitis they restrict death infected hepatocytes, thus allowing...
Background & AimsNecroptosis is a highly inflammatory mode of cell death that has been implicated in causing hepatic injury including steatohepatitis/ nonalcoholic steatohepatitis (NASH); however, the evidence supporting these claims controversial. A comprehensive, fundamental understanding pathways involved liver disease critically underpins rational strategies for therapeutic intervention. We sought to define role and relevance necroptosis pathology.MethodsSeveral animal models human...
Mixed lineage kinase domain-like (MLKL)-dependent necroptosis is thought to be implicated in the death of mycobacteria-infected macrophages, reportedly allowing escape and dissemination microorganism. Given consequent interest developing inhibitors treat Mycobacterium tuberculosis (Mtb) infection, we used human pharmacologic murine genetic models definitively establish pathophysiological role Mtb infection. We observed that infection macrophages remodeled intracellular signaling landscape by...
HIV-1 persists indefinitely in people living with HIV (PLWH) on antiretroviral therapy (ART). If ART is stopped, the virus rapidly rebounds from long-lived latently infected cells. Using a humanized mouse model of infection and CD4
Plasmacytoid dendritic cells (pDCs) represent a unique immune cell type that responds to viral nucleic acids through the rapid production of I interferons. Within hematopoietic system, transcription factor RUNX2 is exclusively expressed in pDCs and required for their peripheral homeostasis. Here, we show plays an essential role promoting pDC localization function. appropriate expression integrin-mediated adhesion machinery, as well down-modulation chemokine receptor CXCR4, which allows...
The lack of expression the suppressor cytokine signalling‐3 (SOCS3) or inactivation negative regulatory capacity SOCS3 has been well documented in rheumatoid arthritis, viral hepatitis and cancer. specific qualitative quantitative consequences deficiency on interleukin‐6 (IL‐6)‐mediated pro‐ anti‐inflammatory responses remain controversial vitro unknown vivo . Mice with a conditional deletion hematopoietic cells develop lethal inflammatory disease during adult life gross histopathological...
Targeting the potent immunosuppressive properties of FOXP3 + regulatory T cells (T regs ) has substantial therapeutic potential for treating autoimmune and inflammatory diseases. Yet, molecular mechanisms controlling reg homeostasis, particularly during inflammation, remain unclear. We report that caspase-8 is a central regulator homeostasis in context-specific manner decisive immune responses. In mouse genetic models, targeting led to accumulation effector resistant apoptotic cell death....
How functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine-tuning CD8αβ co-receptor levels via histone acetylation plays a role in lineage fate. We show lysine acetyltransferase 6A (KAT6A) is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses infection. KAT6A-deficient CD8+ downregulated surface CD8 expression clonal expansion, finding linked to...
Abstract Necroptosis is a lytic and inflammatory form of cell death that highly constrained to mitigate detrimental collateral tissue damage impaired immunity. These constraints make it difficult define the relevance necroptosis in diseases such as chronic persistent viral infections within individual organ systems. The role necroptotic signalling further complicated because proteins essential this pathway, receptor interacting protein kinase 3 (RIPK3) mixed lineage domain-like (MLKL), have...
Caspase-8 transduces signals from death receptor ligands, such as tumor necrosis factor, to drive potent responses including inflammation, cell proliferation or death. This is a developmentally essential function because in utero deletion of endothelial causes systemic circulatory collapse during embryogenesis. Whether also required for cardiovascular patency adulthood was unknown. To address this question, we used an inducible Cre recombinase system delete Casp8 6-week-old conditionally...