A5057959911- Alzheimer's disease research and treatments
- Renin-Angiotensin System Studies
- Hormonal Regulation and Hypertension
- Sodium Intake and Health
- Advanced Glycation End Products research
- Immune cells in cancer
- Immune Cell Function and Interaction
- Protein Structure and Dynamics
- Supramolecular Self-Assembly in Materials
- Adipokines, Inflammation, and Metabolic Diseases
- 3D Printing in Biomedical Research
- Apelin-related biomedical research
- Enzyme Structure and Function
- Cell Adhesion Molecules Research
- Gut microbiota and health
- Silk-based biomaterials and applications
- Eicosanoids and Hypertension Pharmacology
- Platelet Disorders and Treatments
- Tryptophan and brain disorders
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- T-cell and B-cell Immunology
- Circadian rhythm and melatonin
- Immune responses and vaccinations
- Prion Diseases and Protein Misfolding
- Aldose Reductase and Taurine
La Trobe University
2019-2024
Monash University
2010-2024
The University of Melbourne
2006-2023
Monash Alfred Psychiatry Research centre
2022
Baker Heart and Diabetes Institute
2010-2016
Max Delbrück Center
2012-2015
Charité - Universitätsmedizin Berlin
2012-2015
Medizinische Hochschule Hannover
2012-2014
Children's Hospital of Pittsburgh
2014
University of Pittsburgh
2014
A high intake of dietary salt (NaCl) has been implicated in the development hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that a proinflammatory effect boosts activation Th17 cells classical, LPS-induced macrophages (M1). Here, we examined how alternative (M2) is affected by salt. In stark contrast to M1 macrophages, blunted BM-derived mouse stimulated with IL-4 IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction was not associated increased...
Angiotensin (Ang) II induces vascular injury in part by activating innate and adaptive immunity; however, the mechanisms are unclear. We investigated role of interferon (IFN)-γ interleukin (IL)-23 signaling. infused Ang into IFN-γ receptor (IFN-γR) knockout mice wild-type controls, as well treated with neutralizing antibodies against IL-23 IL-17A. II–treated IFN-γR exhibited reduced cardiac hypertrophy, macrophage T-cell infiltration, less fibrosis, arrhythmogenic electric remodeling...
OBJECTIVE Advanced glycation end products (AGEs) and the renin-angiotensin system (RAS) are both implicated in development of diabetic retinopathy. How these pathways interact to promote retinal vasculopathy is not fully understood. Glyoxalase-I (GLO-I) an enzyme critical for detoxification AGEs vascular cell survival. We hypothesized that, retina, angiotensin II (Ang II) downregulates GLO-I, which leads increase methylglyoxal-AGE formation. The type 1 receptor blocker, candesartan,...
Apolipoprotein A-I (apoA-I) is the major protein component of HDL, where it plays an important role in cholesterol transport. The deposition apoA-I derived amyloid associated with various hereditary systemic amyloidoses and atherosclerosis; however, very little known about mechanism formation. Methionine residues are oxidized via several mechanisms vivo to form methionine sulfoxide (MetO), significant levels (MetO-apoA-I) present normal human serum. We investigated effect oxidation on...
Macrophage activation in response to LPS is coupled profound metabolic changes, typified by accumulation of the TCA cycle intermediates citrate, itaconate, and succinate. We have identified that endogenous type I IFN controls cellular citrate/α-ketoglutarate ratio inhibits expression activity isocitrate dehydrogenase (IDH); and, via 13C-labeling studies, demonstrated autocrine carbon flow through IDH LPS-activated macrophages. also found IFN–driven IL-10 contributes inhibition itaconate...
Dietary high salt (HS) is a leading risk factor for mortality and morbidity. Serum sodium transiently increases postprandially but can also accumulate at sites of inflammation affecting differentiation function innate adaptive immune cells. Here, we focus on how changes in extracellular sodium, mimicking alterations the circulation tissues, affect early metabolic, transcriptional, functional adaption human murine mononuclear phagocytes.Using Seahorse technology, pulsed stable...
Metabolic adaptations can directly influence the scope and scale of macrophage activation polarization. Here we explore impact type I interferon (IFNβ) on metabolism its broader cytokine signaling pathways. We find that IFNβ simultaneously increased expression immune-responsive gene 1 itaconate production while inhibiting isocitrate dehydrogenase activity restricting α-ketoglutarate accumulation. also flux glutamine-derived carbon into tricarboxylic acid cycle to boost succinate levels....
Neovascularization is a hallmark feature of retinopathy prematurity and diabetic retinopathy. Type 1 angiotensin receptor blockade reduces neovascularization in experimental prematurity, known as oxygen-induced (OIR). We investigated OIR whether inhibiting aldosterone with the synthase inhibitor FAD286 reduced effectively (valsartan). was induced neonatal Sprague-Dawley rats, they were treated (30 mg/kg per day), valsartan (10 or FAD286+valsartan. The cellular sources synthase,...
Infection and inflammation are able to induce diet-independent Na+-accumulation without commensurate water retention in afflicted tissues, which favors the pro-inflammatory activation of mouse macrophages augments their antibacterial antiparasitic activity. While Na+-boosted host defense against protozoan parasite Leishmania major is mediated by increased expression leishmanicidal NOS2 (nitric oxide synthase 2, inducible), molecular mechanisms underpinning this enhanced with high Na+ (HS)...
The (pro)renin receptor [(P)RR] is implicated in organ pathology. We examined the cellular location of (P)RR and whether a putative antagonist, RILLKKMPSV, corresponding to handle region prorenin prosegment (handle peptide [HRP]) influences angiogenesis, inflammation, neuronal glial function rat retina. was localized retinal vessels, endothelial cells, pericytes, but most immunolabeling ganglion cells glia. HRP (1 mg/kg per day by IP injection) reduced physiological angiogenesis developing...
The in vivo aggregation of proteins into amyloid fibrils suggests that cellular mechanisms normally prevent or reverse this have failed. small heat-shock molecular chaperone protein αB-crystallin (αB-c) inhibits formation and colocalizes with plaques; however, the physiological reason for localization remains unexplored. Here, using apolipoprotein C-II (apoC-II) as a model fibril-forming system, we show αB-c binds directly to mature (Kd 5.4 ± 0.5 μM). In doing so, stabilized from...
Inflammation and infection can trigger local tissue Na+ accumulation. This Na+-rich environment boosts proinflammatory activation of monocyte/macrophage-like cells (MΦs) their antimicrobial activity. Enhanced Na+-driven MΦ function requires the osmoprotective transcription factor nuclear activated T 5 (NFAT5), which augments nitric oxide (NO) production contributes to increased autophagy. However, mechanism sensing in MΦs remained unclear. High extracellular levels (high salt [HS]) a...
Tetraspanins regulate key processes in immune cells; however, the function of leukocyte-restricted tetraspanin CD53 is unknown. Here we show that essential for lymphocyte recirculation. Lymph nodes Cd53
Leishmania are sandfly-transmitted protists that induce granulomatous lesions in their mammalian host. Although infected host cells these tissues can exist different activation states, the extent to which intracellular parasites stages also growth or physiological states remains poorly defined. Here, we have mapped spatial distribution of metabolically quiescent and active subpopulations mexicana dermal granulomas susceptible BALB/c mice, using vivo heavy water labeling ultra high-resolution...
Pancreatic β cells store insulin within secretory granules which undergo exocytosis upon elevation of blood glucose levels. Crinophagy and autophagy are instead responsible to deliver damaged or old acidic lysosomes for intracellular degradation. However, excessive consumption can impair cell function cause diabetes. Atp6ap2 is an essential accessory component the vacuolar ATPase required lysosomal degradative functions autophagy. Here, we show that Cre recombinase-mediated conditional...