A5029858068- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- COVID-19 Clinical Research Studies
- Cancer Immunotherapy and Biomarkers
- SARS-CoV-2 and COVID-19 Research
- Pregnancy and Medication Impact
- COVID-19 Impact on Reproduction
- Adenosine and Purinergic Signaling
- Phagocytosis and Immune Regulation
- Long-Term Effects of COVID-19
- Cytomegalovirus and herpesvirus research
- Adolescent and Pediatric Healthcare
- CAR-T cell therapy research
- Inhalation and Respiratory Drug Delivery
- Workplace Violence and Bullying
- RNA Interference and Gene Delivery
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Stress and Burnout Research
- Influenza Virus Research Studies
- Metabolomics and Mass Spectrometry Studies
- Congenital heart defects research
The University of Melbourne
2016-2025
Peter Doherty Institute
2016-2025
Australian Research Council
2015-2023
Brigham and Women's Hospital
2022-2023
Harvard University
2022
ORCID
2020
ARC Centre of Excellence in Advanced Molecular Imaging
2018
Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to MR1-restricted MAIT cell receptors (TCRs), we demonstrate are detectable broad range tissues C57BL/6 and BALB/c mice. These include CD4−CD8−, CD4−CD8+, CD4+CD8− subsets, their frequency varies tissue- strain-specific manner. Mouse CD44hiCD62Llo memory phenotype produce high levels IL-17A, whereas other...
Mucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human cells. They are usually defined using combinations non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18Rα and CD26. The development MR1-Ag tetramers now permits the specific identification MAIT based on T-cell receptor specificity. Here, we compare these approaches for identifying show that surrogate not always accurate in cells, particularly CD4+ fraction. Moreover, while all cell...
MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These develop intrathymically through three-stage process, but events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis mice humans, we studied changing transcriptional landscape accompanies transition each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic...
Abstract Mucosal-associated invariant T (MAIT) cells express an TRAV1/TRAJ33 TCR-α chain and are restricted to the MHC-I-like molecule, MR1. Whether MAIT cell development depends on this is unclear. Here we generate Traj33 -deficient mice show that they highly depleted of cells; however, a residual population remains can respond exogenous antigen in vitro or pulmonary Legionella challenge vivo. These include some Trav1 + TCRs with conservative Traj -gene substitutions, others - broad range...
Abstract The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control metastatic B16F10 growth relative to mice. Analyses this interplay human samples reveal high expression a cell gene signature negatively impacts the prognostic significance cells. Paradoxically, pre-pulsing tumors with antigens, or activating vivo, enhances anti-tumor and E0771 mouse models,...
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...
Vγ9Vδ2 T cells are the largest population of γδ in adults and can play important roles providing effective immunity against cancer infection. Many studies have suggested that peripheral derived from fetal liver thymus postnatal plays little role development these cells. More recent evidence may also develop postnatally thymus. Here, we used high-dimensional flow cytometry, transcriptomic analysis, functional assays, precursor-product experiments to define pathway We identify three distinct...
Abstract NK cells and CD8 T use cytotoxic molecules to kill virally infected tumor cell targets. While perforin granzyme B (GzmB) are the most commonly studied lytic molecules, less is known about K (GzmK). However, this has been recently associated with improved prognosis in solid tumors. In study, we show that, humans, GzmK predominantly expressed by innate-like lymphocytes, as well a newly identified population of GzmK+CD8+ non– mucosal-associated invariant characteristics. We found that...
Interleukin (IL)-17–producing CD8+ T (Tc17) cells have emerged as key players in host-microbiota interactions, infection, and cancer. The factors that drive their development, contrast to interferon (IFN)-γ–producing effector cells, are not clear. Here we demonstrate the transcription factor TCF-1 (Tcf7) regulates cell fate decisions double-positive (DP) thymocytes through sequential suppression of MAF RORγt, parallel with TCF-1–driven modulation chromatin state. Ablation resulted enhanced...
Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components longitudinal blood respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected blood, however, receptor-binding domain (RBD)-specific IgM IgG seroconversion is enhanced specimens. neutralization activity correlates RBD-specific levels. Cytokines/chemokines vary between...
Mucosal-associated invariant T (MAIT) cells, natural killer (NKT) and γδT cells are collectively referred to as 'unconventional cells' due their recognition of non-peptide antigens restriction MHC-I-like molecules. However, the factors controlling widely variable frequencies between individuals organs poorly understood. We demonstrated that MAIT increased in NKT or cell-deficient mice highly expand lacking both cell types. TCRα repertoire analysis thymocytes revealed altered Trav segment...
Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, after hospital admission, persisting until death. Recovered had low OLAH expression throughout hospitalization. High levels were also...
Abstract Mucosal-associated invariant T (MAIT) cells are important for immune responses against microbial infections. Although known to undergo marked numerical changes with age in humans, our understanding of how MAIT altered during different phases across the human life span is largely unknown. also abundant tissues, study focuses on cell analyses blood. Across span, we show that naive-like umbilical cord blood switch a central/effector memory-like profile sustained into older age. Whereas...
Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to in unvaccinated pregnant and nonpregnant women acute convalescent COVID-19, quantifying 217 parameters. Humoral were similar women, although our systems serology approach revealed distinct antibody FcγR profiles between women. Cellular analyses demonstrated marked differences NK cell unconventional T...
Abstract There are reports of poor working conditions for early and mid-career academics (EMCAs) in universities, however, empirical data using validated tools scarce. We conducted an online, cross-sectional survey to assess workplace satisfaction, exposure abuse, mental health. Participants included employees medical health faculties two the largest Australian surveyed between October 2020 January 2021. Overall, 284 participants responded. Many reported job insecurity: half (50.7%) on...