A5074094157- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Malaria Research and Control
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Mosquito-borne diseases and control
- Inflammatory Bowel Disease
- Cancer Cells and Metastasis
- Viral Infections and Vectors
- Congenital gastrointestinal and neural anomalies
- interferon and immune responses
- Complement system in diseases
- Immunotherapy and Immune Responses
- Lymphoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Gut microbiota and health
- Immune cells in cancer
- Breast Cancer Treatment Studies
- Research on Leishmaniasis Studies
- Aquaculture disease management and microbiota
- Evolution and Genetic Dynamics
- Cancer and Skin Lesions
- Microscopic Colitis
- Helicobacter pylori-related gastroenterology studies
- CAR-T cell therapy research
Garvan Institute of Medical Research
2021-2025
UNSW Sydney
2022-2025
The Kinghorn Cancer Centre
2021-2023
Southern Methodist University
2023
Wellcome Sanger Institute
2018-2021
QIMR Berghofer Medical Research Institute
2013-2019
The University of Queensland
2014-2018
National Institute of Malaria Research
2014
Charing Cross Hospital
1980-1990
Abstract The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing response to functional requirements environmental exposures. Here, comprehensively map cell lineages, we use single-cell RNA sequencing antigen receptor analysis almost half a million cells from up 5 anatomical regions 11 distinct healthy paediatric adult gut. This reveals existence transcriptionally BEST4 epithelial tract. Furthermore, implicate IgG sensing as function...
Computational modeling defines T helper cell differentiation toward multiple fates during experimental malaria.
Human gut development requires the orchestrated interaction of differentiating cell types. Here, we generate an in-depth single-cell map developing human intestine at 6-10 weeks post-conception. Our analysis reveals transcriptional profile cycling epithelial precursor cells; distinct from LGR5-expressing cells. We propose that these cells may contribute to differentiated subsets via generation stem and receive signals surrounding mesenchymal Furthermore, draw parallels between transcriptomes...
Many pathogens, including viruses, bacteria, and protozoan parasites, suppress cellular immune responses through activation of type I IFN signaling. Recent evidence suggests that suppression susceptibility to the malaria parasite, Plasmodium, is mediated by IFN; however, it unclear how suppresses immunity blood-stage Plasmodium parasites. During experimental severe malaria, CD4+ Th cell are suppressed, conventional DC (cDC) function curtailed unknown mechanisms. Here, we tested hypothesis...
Abstract Bats have adapted to pathogens through diverse mechanisms, including increased resistance – rapid pathogen elimination, and tolerance limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease were discovered, but underpinning remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead Here, we test whether such...
Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations this have focused on antigenic variation by Plasmodium, but considered less whether host production of parasite-specific antibody is sub-optimal. In particular, unclear immune factors might limit responses. Here, we explored the effect Type I Interferon signalling via IFNAR1...
Abstract Despite extensive mapping of long noncoding RNAs in immune cells, their function vivo remains poorly understood. In this study, we identify over 100 that are differentially expressed within 24 h Th1 cell activation. Among those, show suppression Malat1 is a hallmark CD4+ T activation, but its complete deletion results more potent responses to infection. This because Malat1−/− and Th2 cells express lower levels the immunosuppressive cytokine IL-10. vivo, reduced IL-10 expression...
Abstract The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics surge diseases 1,2 has fuelled efforts to catalogue cells constituting tissues health disease 3 . Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy development adulthood. We uniformly processed 385 samples from 189 controls using newly developed automated quality control approach (scAutoQC),...
Humoral immunity develops in the spleen during blood-stage Plasmodium infection. This elicits parasite-specific IgM and IgG, which control parasites protect against malaria. Studies mice have elucidated cells molecules driving humoral to Plasmodium, including CD4+ T cells, B interleukin (IL)-21 ICOS. IL-6, a cytokine readily detected Plasmodium-infected humans, is recognized other systems as driver of immunity. Here, we examined effect infection-induced IL-6 on Plasmodium. Using P. chabaudi...
Abstract We describe an MHC class II (I-Ab)–restricted TCR transgenic mouse line that produces CD4+ T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a cell hybridoma generated to blood-stage berghei ANKA (PbA). PbT-II responded all species and stages tested so far, including rodent (PbA, P. NK65, chabaudi AS, yoelii 17XNL) human (Plasmodium falciparum) parasites as well irradiated PbA sporozoites. can provide help generation of Ab infection control this...
Abstract Background Primary sclerosing cholangitis (PSC) is a chronic progressing cholestatic disease that often co-occurs with inflammatory bowel (PSC-IBD). PSC-IBD affecting the colon (PSC-UC) likened clinically to ulcerative colitis (UC), however differences include right dominance, less severe presentation and greater lifetime risk of colorectal cancer. Methods We combine single-cell mRNA antigen receptor sequencing, 16S ribosomal RNA gene analysis spatial transcriptomics profile mucosal...
Hepatic fibrosis induced by egg deposition is the most serious pathology associated with chronic schistosomiasis, in which hepatic stellate cell (HSC) plays a central role. While effect of Schistosoma mansoni eggs on fibrogenic phenotype HSCs has been investigated, studies determining S. japonicum are lacking. Disease caused much more severe than that resulting from infection so it important to compare pathologies these two parasites, determine whether this due species interacting...
Abstract Differentiation of CD4+ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection blood-stage Plasmodium parasites, yet their influence over cell remains unclear. In this study, we used Plasmodium-reactive TCR transgenic T cells, termed PbTII during nonlethal P. chabaudi AS and yoelii 17XNL infection mice, examine development vivo. We found no role caspase1/11, stimulator IFN genes, or mitochondrial...
Severe malaria and associated high parasite burdens occur more frequently in humans lacking robust adaptive immunity to Plasmodium falciparum Nevertheless, the host may partly control blood-stage numbers while is gradually established. Parasite has typically been attributed enhanced removal of parasites by host, although vivo quantification this phenomenon remains challenging. We used a unique approach determine fate single cohort semisynchronous, berghei ANKA- or yoelii 17XNL-parasitized...
Plasmodium parasites invade and multiply inside red blood cells (RBC). Through a cycle of maturation, asexual replication, rupture release multiple infective merozoites, parasitised RBC (pRBC) can reach very high numbers in vivo, process that correlates with disease severity humans experimental animals. Thus, controlling pRBC prevent or ameliorate malaria. In endemic regions, circulating parasite-specific antibodies associate immunity to parasitemia. Although vitro assays reveal protective...