- Liver physiology and pathology
- Organ Transplantation Techniques and Outcomes
- Liver Disease Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Pediatric Hepatobiliary Diseases and Treatments
- Pancreatic function and diabetes
- Cholangiocarcinoma and Gallbladder Cancer Studies
- MicroRNA in disease regulation
- Liver Disease and Transplantation
- Genetic and Kidney Cyst Diseases
- RNA modifications and cancer
- Drug-Induced Hepatotoxicity and Protection
- 3D Printing in Biomedical Research
- Metabolism, Diabetes, and Cancer
- Cancer Cells and Metastasis
- Multiple Myeloma Research and Treatments
- Congenital Anomalies and Fetal Surgery
- Hedgehog Signaling Pathway Studies
- Actinomycetales infections and treatment
- Diabetes Treatment and Management
- Cancer-related Molecular Pathways
- Retinal Diseases and Treatments
- Optimism, Hope, and Well-being
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
MRC Centre for Regenerative Medicine
2016-2025
University of Edinburgh
2016-2025
Curtin University
2013-2025
The University of Western Australia
2016
Harry Perkins Institute of Medical Research
2016
Medical Research Council
2016
Cold Spring Harbor Laboratory
2016
Tauranga Hospital
2008
•Primary BMDMs localised to liver and spleen within hours following intravenous injection in mice.•AAMs were highly phagocytic i.v. transfer elicited reductions necrotic area, HMGB1 translocation, hepatic neutrophil infiltration.•AAM reduced inflammatory mediators stimulated hepatocyte/endothelium proliferation injured liver.•Injection of clinical-grade human AAMs could partially recapitulate the efficacy murine immunocompetent mice. Background & AimFollowing acetaminophen (APAP) overdose,...
Cellular senescence is a mechanism that provides an irreversible barrier to cell cycle progression prevent undesired proliferation. However, under pathological circumstances, can adversely affect organ function, viability and regeneration. We have developed mouse model of biliary senescence, based on the conditional deletion Mdm2 in bile ducts control Krt19 promoter, exhibits features disease. Here we report senescent cholangiocytes induce profound alterations cellular signalling...
Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except transplantation. New therapies urgently required. We have therefore purified human epithelial cells (hBECs) from livers that were not used hBECs tested as a cell therapy in mouse model of which the conditional deletion Mdm2 cholangiocytes causes senescence, strictures, fibrosis. expandable phenotypically stable help restore...
Significance Clinical outcomes in cholangiocarcinoma (CC) are poor; few patients candidates for curative resection, and palliative chemotherapy produces only modest effects on survival. With an increasing incidence, new targets urgently needed. Notch has been identified as having potential to induce CC when transgenically overexpressed, this study aimed characterize how endogenous might drive tumorigenesis. We identify the atypical receptor Notch3 differentially overactivated CCs humans,...
•Fn14 is upregulated on tumour cells and CAFs, TWEAK expressed by TAMs in human CCA.•TWEAK/Fn14 are progressively during rodent development.•TWEAK/Fn14 signalling induces TAM accumulation via TWEAK-inducible MCP-1 chemotaxis which can be blocked vivo.•TWEAK-inducible factors from pattern macrophages to a TAM-like phenotype.•TWEAK overexpression experimental formation drives CAF proliferation, collagen deposition increases mice. Background & AimsCholangiocarcinoma (CCA) cancer of the hepatic...
The role of the liver and endocrine pancreas in development hyperinsulinemia different types obesity remains unclear. Sedentary rats (160 g) were fed a low-fat-diet (LFD, chow 13% kcal fat), high-fat-diet (HFD, 35% or HFD+ 30% ethanol+ fructose (HF-EFr, 22% fat). Overnight-fasted culled after one, four eight weeks. Pancreatic hepatic mRNAs isolated for subsequent RT-PCR analysis. After weeks, body weights increased three-fold LFD group, 2.8-fold HFD 2.4-fold HF-EFr (p < 0.01). HF-EFr-fed...
Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by progressive loss of biliary tract architecture) continue to occur after transplantation, negatively affecting function and frequently leading graft retransplantation. To study biological effects organ preservation before we generated murine models that recapitulate procurement static cold storage. In these...
Autologous macrophage therapy represents a potentially significant therapeutic advance for the treatment of severe progressive liver cirrhosis. Administration macrophages has been shown to reduce inflammation and drive fibrotic scar breakdown tissue repair in relevant models. This approach is being assessed safety feasibility first-in-human trial (MAcrophages Therapy CirrHosis [MATCH] trial).We outline development validation phases GMP production. includes use CliniMACS Prodigy cell sorting...
Notch signaling promotes progenitor cell proliferation but inhibits hepatocyte differentiation during liver repair.
Abstract Background and Aim Acetaminophen (APAP) induced acute liver injury (ALI), the leading cause failure in western world, has limited treatment options. APAP toxicity results massive hepatic necrosis secondary infiltrating monocytes neutrophils, which contribute to pathogenesis. Semaphorin 7a (Sema7a), a chemoattractant modulator of is potential therapeutic target other conditions, but its role APAP-ALI unexplored. Methods Wild-type (WT) Sema7a knockout (KO) mice were examined during...
Cancer frequently arises in epithelial tissues subjected to repeated cycles of injury and repair. Improving our understanding tissue regeneration is, therefore, likely reveal novel processes with inherent potential for aberration that can lead carcinoma. These highly conserved regenerative mechanisms are increasingly understood the liver associated special characteristics underlie organ's legendary capacity restoration size function following even severe or chronic injury. The nature...