A5068722957- Immune cells in cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- Diabetes and associated disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Phagocytosis and Immune Regulation
- Neonatal Respiratory Health Research
- Immune Response and Inflammation
- Bone Metabolism and Diseases
- Angiogenesis and VEGF in Cancer
- Regulation of Appetite and Obesity
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Advanced Proteomics Techniques and Applications
- Diet, Metabolism, and Disease
- Hematological disorders and diagnostics
- Neuroblastoma Research and Treatments
- Tryptophan and brain disorders
- Pancreatic function and diabetes
- Peroxisome Proliferator-Activated Receptors
- Liver physiology and pathology
- Heme Oxygenase-1 and Carbon Monoxide
- Diabetes Management and Research
Translational Research Institute
2015-2025
The University of Queensland
2015-2025
Mater Research
2015-2025
QIMR Berghofer Medical Research Institute
2024
Homozygous mutation of the Csf1r locus ( Csf1rko ) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis mechanisms underlying phenotypic impacts mutation, we bred a rat allele inbred dark agouti (DA) genetic background -mApple reporter transgene. The led almost complete loss embryonic macrophages ablation most adult tissue macrophage populations. We extended previous phenotype early development reveal on musculoskeletal proliferation...
Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress β-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate resistance in preclinical models diabetes. In clinical trials long-acting forms IL-22 have led to increased proliferation skin intestine, where...
Mutations in the human CSF1R gene have been associated with dominant and recessive forms of neurodegenerative disease. Here we describe impacts Csf1r mutation rat on development brain. Diffusion imaging indicated small reductions major fiber tracts that may be part ventricular enlargement. RNA-seq profiling revealed a set 105 microglial markers depleted all brain regions Csf1rko rats. There was no evidence region or sex-specific expression microglia-associated transcripts. Other than...
Abstract The IL-22RA1 receptor is highly expressed in the pancreas, and exogenous IL-22 has been shown to reduce endoplasmic reticulum oxidative stress human pancreatic islets promote secretion of high-quality insulin from beta-cells. However, endogenous role signaling on these cells remains unclear. Here, we show that antibody neutralisation cultured leads impaired quality increased cellular stress. Through generation mice lacking IL-22ra1 specifically alpha- or beta-cells, demonstrate...
Abstract Macrophages are present in large numbers every tissue the body where they play critical roles development and homeostasis. They exhibit remarkable phenotypic functional diversity, underpinning their adaptation to specialized each niche. CSF1, signaling through CSF1 receptor, which is restricted monocyte-macrophage lineage cells adults, a growth factor controlling macrophage proliferation, differentiation, many aspects of mature function. We have generated reporter rat, utilizing...
ABSTRACT Amino acid substitutions in the kinase domain of human CSF1R gene are associated with autosomal dominant adult-onset leukoencephalopathy axonal spheroids and pigmented glia (ALSP). To model disease, we created a disease-associated mutation (pGlu631Lys; E631K) mouse Csf1r locus. Homozygous (Csf1rE631K/E631K) phenocopied knockout, prenatal mortality or severe postnatal growth retardation hydrocephalus. Heterozygous delayed expansion tissue macrophage populations most organs. Bone...
Adaptation to existence outside the womb is a key event in life of mammal. The absence macrophages rats with homozygous mutation colony-stimulating factor 1 receptor ( Csf1r) gene Csf1rko ) severely compromises pre-weaning somatic growth and maturation organ function. Transfer wild-type bone marrow cells (BMT) at weaning rescues tissue macrophage populations permitting normal development long-term survival. To dissect phenotype function postnatal development, we generated transcriptomic...
Abstract Interleukin-34 (IL34) and colony stimulating factor 1 (CSF1) signal through a shared receptor (CSF1R) to control macrophage survival, differentiation function. Here we describe the impact of loss function mutation in rat Il34 gene. −/− rats showed partial reduction macrophages within squamous epithelia (Langerhans-like cells) testis. In brain, microglia brain-associated were selectively depleted grey matter. A gradient microglial density cortex suggests that CSF1 can diffuse...
Background and Aims: In the context of hepatobiliary liver transplant surgery, ischemia-reperfusion (I/R) injury can occur due to temporary interruption blood flow organ followed by a potentially damaging inflammatory response reperfusion. As macrophages promote growth resolution chronic fibrosis, we tested hypothesis that stimulation monocytes with Colony Stimulating Factor 1 (CSF1) could repair after I/R injury. Methods: We investigated impact perisurgical treatment long-circulating...
Macrophage and osteoclast proliferation, differentiation survival are regulated by colony-stimulating factor 1 receptor (CSF1R) signaling. Osteopetrosis associated with Csf1 Csf1r mutations has been attributed to the loss of osteoclasts deficiency in bone resorption. Here, we demonstrate that homozygous mutation rat leads delayed postnatal skeletal ossification substantial osteal macrophages addition osteoclasts. Osteosclerosis site-specific abnormalities were reversed intraperitoneal...
Adipose tissue expansion occurs through a combination of hypertrophy existing adipocytes and generation new via the process hyperplasia, which involves proliferation subsequent differentiation preadipocytes. Deficiencies in hyperplasia contribute to adipose dysfunction association obesity with chronic cardiometabolic diseases. Thus, increased understanding hyperplastic pathways may be expected afford novel therapeutic strategies. We have reported that fibroblast growth factor (FGF)-1...
The contribution of environmental factors to pancreatic islet damage in type 1 diabetes remains poorly understood. In this study, we crossed mice susceptible diabetes, where parental male (CD8+ T cells specific for IGRP206-214; NOD8.3) and female (NOD/ShiLt) were randomized a diet either low or high AGE content maintained on throughout pregnancy lactation. After weaning, NOD8.3+ offspring identified the same feeding regimen until day 28 life. A diet, from conception early postnatal life,...
Abstract Macrophages are an abundant cell population in the placenta and developing embryo appear to be involved processes of vascularization, morphogenesis, organogenesis, hematopoiesis. The proliferation, differentiation, survival dependent on signals from macrophage colony-stimulating factor receptor, CSF1R. Aside role macrophages, Csf1r mRNA is highly expressed placental trophoblasts. To explore function macrophages embryonic development, we analyzed impact homozygous null mutation...
ABSTRACT Resident and recruited macrophages control the development proliferation of liver. We have previously shown in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte promoted repair models acute hepatic injury mice. Here, we investigated impact CSF1-Fc on resolution advanced fibrosis liver regeneration, using non-resolving toxin-induced model chronic C57BL/6J Co-administration exposure to thioacetamide (TAA)...
Hypoadiponectinemia and adiponectin resistance are implicated in the aetiology of obesity-related cardiometabolic disorders, hence represent a potential therapeutic axis. Here we characterised effects vivo electrotransfer-mediated overexpression receptors, AdipoR1 or AdipoR2, into tibialis anterior muscle (TAM) lean obese mice. In mice, TAM-specific (TAMR1) AdipoR2 (TAMR2) increased phosphorylation AMPK, AKT ERK expression insulin responsive glucose transporter glut4. contrast, only TAMR2...
Abstract Homozygous null mutation of the Csf1r gene ( Csf1rko ) in rats leads to loss most tissue macrophage populations and pleiotropic impacts on postnatal growth organ maturation, leading early mortality. The phenotype can be reversed by intraperitoneal transfer WT BM cells (BMT) at weaning. Here, we used a ‐mApple transgenic reporter track fate donor‐derived cells. Following BMT into recipients, mApple +ve restored IBA1 + every tissue. However, monocytes, neutrophils, B BM, blood,...
Type 2 diabetes (T2D) is a well-known risk factor for tuberculosis (TB), but little known about pre-diabetes and the relative contribution of impaired glucose tolerance vs. obesity towards susceptibility to TB. Here, we developed preclinical model Mice fed high fat diet (HFD) 12 weeks presented with hyperinsulinemia compared mice normal chow (NCD). Infection M. (Mtb) H 37 R v after onset dysglycemia was associated significantly increased lung pathology, lower concentrations TNF-α, IFN-γ,...