A5056363094- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Immune Response and Inflammation
- Inflammasome and immune disorders
- CAR-T cell therapy research
- Tuberculosis Research and Epidemiology
- Hepatitis C virus research
- NF-κB Signaling Pathways
- COVID-19 Clinical Research Studies
- RNA Interference and Gene Delivery
- Liver Disease Diagnosis and Treatment
- Virus-based gene therapy research
- Mycobacterium research and diagnosis
- Immune responses and vaccinations
- Immune cells in cancer
- Adipose Tissue and Metabolism
- HIV Research and Treatment
- Phagocytosis and Immune Regulation
- Cancer-related Molecular Pathways
- Cytomegalovirus and herpesvirus research
Walter and Eliza Hall Institute of Medical Research
2016-2025
The University of Melbourne
2016-2025
University of Technology Sydney
2025
Centenary Institute
2024-2025
Peter MacCallum Cancer Centre
2021-2022
National Health and Medical Research Council
2021-2022
Victorian Comprehensive Cancer Centre
2017-2021
CSIRO Manufacturing
2020
Immune Regulation (United Kingdom)
2020
Ontario Institute for Cancer Research
2004-2011
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...
Puma is an essential mediator of p53-dependent and -independent apoptosis in vivo. In response to genotoxic stress, induced a manner. However, the transcription factor driving up-regulation p53-independent apoptotic stimuli has yet be identified. Here, we show that FOXO3a up-regulates expression cytokine or growth deprivation. Importantly, dysregulated Akt signaling lymphoid cells attenuated induction upon withdrawal. Our results suggest Puma, together with another BH3 only member, Bim,...
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 Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics the prevention treatment of COVID-19. We identified high-affinity nanobodies SARS-CoV-2 receptor-binding domain found that nanobody cocktails consisting two noncompeting were able to block ACE2 engagement with RBD variants present in human populations potently neutralize both wild-type N501Y D614G variant at low concentrations. Prophylactic...
We used mutant Fas-deficient ( lpr ) or Bim-deficient mice to investigate the role of death receptor and Bcl-2-regulated apoptotic pathways in terminating a physiological T cell response herpes simplex virus infection. In WT CD8 + antigen-specific cells were deleted after viral clearance. contrast, immune was not terminated despite clearance, accumulated spleen. Thus, Bim is dispensable for clearance but necessary activated when responses are terminated. These findings have implications...
TNF-alpha antagonists are widely used in the treatment of inflammatory and autoimmune diseases, but their use is associated with reactivation latent infections. This highlights importance immunity to certain pathogens raises concerns that critical aspects immune function impaired its absence. Unfortunately, role regulation T cell responses clouded by a myriad contradictory reports. Here, we show for receptors, TNFR1 TNFR2, specifically antitumor immunity. TNF-alpha-deficient mice exhibited...
Histone deacetylase inhibitors (HDACi) can elicit a range of biological responses that affect tumor growth and survival, including inhibition cell cycle progression, induction cell-selective apoptosis, suppression angiogenesis, modulation immune responses, show promising activity against hematological malignancies in clinical trials. Using the Emu-myc model B lymphoma, we screened tumors with defined genetic alterations apoptotic pathways for therapeutic responsiveness to HDACi vorinostat....
Programmed cell death contributes to host defense against pathogens. To investigate the relative importance of pyroptosis, necroptosis, and apoptosis during Salmonella infection, we infected mice macrophages deficient for diverse combinations caspases-1, -11, -12, -8 receptor interacting serine/threonine kinase 3 (RIPK3). Loss caspase-8-driven apoptosis, or necroptosis had minor impact on control. However, combined deficiency these pathways caused loss bacterial control in their macrophages,...
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...
Abstract MLKL is the essential effector of necroptosis, a form programmed lytic cell death. We have isolated mouse strain with single missense mutation, Mlkl D139V , that alters two-helix ‘brace’ connects killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation salivary glands mediastinum. The normal embryonic development homozygotes until birth, absence...