A5063419360- Diet and metabolism studies
- Chemokine receptors and signaling
- Diet, Metabolism, and Disease
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Asthma and respiratory diseases
- Dermatology and Skin Diseases
- Allergic Rhinitis and Sensitization
- melanin and skin pigmentation
- Inflammasome and immune disorders
- Cutaneous Melanoma Detection and Management
- Renal function and acid-base balance
- Cell Adhesion Molecules Research
- Nutritional Studies and Diet
- Immune Response and Inflammation
- Adipose Tissue and Metabolism
- Gut microbiota and health
- Antimicrobial Peptides and Activities
- Helicobacter pylori-related gastroenterology studies
Monash University
2015-2023
Australian Regenerative Medicine Institute
2017-2023
The Alfred Hospital
1998
Diet and the gut microbiota may underpin numerous human diseases. A major metabolic product of commensal bacteria are short-chain fatty acids (SCFAs) that derive from fermentation dietary fibre. Here we show diets deficient or low in fibre exacerbate colitis development, while very high intake SCFA acetate protects against colitis. SCFAs binding to 'metabolite-sensing' receptors GPR43 GPR109A non-haematopoietic cells mediate these protective effects. The inflammasome pathway has hitherto...
The chemokine receptor CCR6 marks subsets of T cells and innate lymphoid that produce IL-17 IL-22, as such may play a role in the recruitment these to certain inflammatory sites. However, precise has been controversial, part because no effective monoclonal antibody (mAb) inhibitors against this exist for use mouse models inflammation. We circumvented problem using transgenic mice expressing human (hCCR6) under control its native promoter (hCCR6-Tg/mCCR6-/-). also developed fully humanized...
pH sensing by GPR65 regulates various inflammatory conditions, but its role in skin remains unknown. In this study, we performed a phenome-wide association study and report that the T allele of GPR65-intronic single-nucleotide polymorphism rs8005161, which reduces signaling, showed significant with atopic dermatitis, addition to bowel diseases asthma, as previously reported. Consistent genetic humans, show deficiency mice resulted markedly exacerbated disease MC903 experimental model...
Chemokines and their receptors are pivotal for the trafficking of leukocytes during immune responses, host defense. However, cell migration also contributes to a wide variety autoimmune chronic inflammatory diseases. Compelling evidence suggests that both CXCR3 CCR6 chemokine play crucial roles in pathological Th1 Th17 cells course certain The use two or more by pathogenic may explain why targeting individual has proven disappointing clinic. We therefore hypothesized simultaneous with...
Neutrophils are the most abundant effector cells of innate immune system and represent first line defense against infection. However, in many common pathologies, including autoimmune diseases, excessive recruitment activation neutrophils can drive a chronic inflammatory response leading to unwanted tissue destruction. Several strategies have been investigated tackle pathologic neutrophil biology, thus provide novel therapy for diseases. The chemokine receptor CXCR2 plays crucial role...
Between 6 and 14% of malignant melanomas have been reported to occur in a familial pattern. In this study 785 melanoma patients from the Victorian Melanoma Service private practice dermatologist were assessed for total number melanocytic naevi, dysplastic naevi other clinical characteristics categorized according whether there was family history melanoma. It found that presence 100 or more six blue eyes patient with significantly associated Patients two members likely develop at younger age...
Abstract High blood pressure (BP) is the most common cause of death globally, due to increasing risk cardiovascular diseases. Dietary fiber regulates BP through gut microbial production acidic metabolites known as short-chain fatty acids (SCFAs). The specific mechanisms how SCFAs regulate are still emerging. In a phenome-wide association study, we identified that proton-sensing G-protein-coupled receptor GPR65 gene associated with hypertension and its end-organ damage phenotypes. We...
Targeting CXCR1 and CXCR2 chemokine receptors to block neutrophil migration sites of inflammation is a promising therapeutic approach for various inflammatory autoimmune diseases. However, assessing the translational potential such therapies using mouse models challenging due unclear expression at protein level. Although has been well characterized in both mice humans, protein-level (mCXCR1) remains controversial. To address this issue, we generated novel human knock-in (hCXCR1 KI) model...
Objective: Dietary fibre regulates blood pressure (BP) through gut microbial production of acidic metabolites called short-chain fatty acids (SCFAs). The environment in the large intestine activates a proton-sensing G-protein coupled receptor, GPR65. We aimed to characterize luminal pH hypertensive patients and normotensive individuals, validate murine model that dietary intake is critical determinant for intestinal pH. Furthermore, we determine whether pH-sensing by GPR65 mediates...
High fibre (HF) diet protects against hypertension via the production of acidic metabolites, e.g. short-chain fatty acids, by gut microbiota. While these metabolites have a direct role in blood pressure (BP) regulation, their nature may activate proton-sensing receptors, which anti-inflammatory functions. G-protein coupled receptor 65 (GPR65) is activated around pH 6.5 and critical for homeostasis. We hypothesized that GPR65 involved cardiovascular protection dietary fibre. first measured...