A5025919973- Phagocytosis and Immune Regulation
- Pancreatic function and diabetes
- Extracellular vesicles in disease
- Advanced Glycation End Products research
- Erythrocyte Function and Pathophysiology
- Angiogenesis and VEGF in Cancer
- Renal Transplantation Outcomes and Treatments
- Cell Adhesion Molecules Research
- Kruppel-like factors research
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Muscle Physiology and Disorders
- Hippo pathway signaling and YAP/TAZ
- Pulmonary Hypertension Research and Treatments
- CAR-T cell therapy research
- Chronic Kidney Disease and Diabetes
- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Heme Oxygenase-1 and Carbon Monoxide
- Regulation of Appetite and Obesity
- Pain Mechanisms and Treatments
- Organ Donation and Transplantation
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Renin-Angiotensin System Studies
Westmead Institute for Medical Research
2019-2025
The University of Sydney
2020-2025
Aarhus University
2023
University of Fribourg
2015-2021
Westmead Hospital
2021
University of Pittsburgh
2016-2020
Spanish National Centre for Cardiovascular Research
2016
Uppsala University
2011
Centro Nacional de Biotecnología
2010
Biomedical Research Networking Center on Neurodegenerative Diseases
2010
Abstract Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides are fused with cationic uptake moieties or formulated into nanoparticles facilitate delivery, but these systems typically lack potency due low and/or entrapment degradation in endolysosomal compartments. Because most delivery reagents comprise lipids polymers, there is a of specifically optimized deliver cargo. Herein, we demonstrate the...
Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1−/− mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1–CD47 axis upregulated in human PH promotes arterial vasculopathy. analyzed molecular signature functional response of lung tissue distal arteries (PAs) individuals with (n = 23) without 16) PH. Compared controls, lungs PAs patients showed induction endothelin-1/endothelin A receptor (ET-1/ETA) protein mRNA. In control PAs, treatment exogenous TSP1 inhibited...
Fluid shear stress stimulates endothelial nitric oxide synthase (eNOS) activation and (NO) production through multiple kinases, including protein kinase A (PKA), AMP-activated (AMPK), AKT Ca2+/calmodulin-dependent II (CaMKII). Membrane-associated guanylate (MAGUK) with inverted domain structure-1 (MAGI1) is an adaptor that stabilizes epithelial cell-cell contacts. The aim of this study was to assess the unknown role cell MAGI1 in response fluid stress. We show constitutive expression...
The aged population is currently at its highest level in human history and expected to increase further the coming years. In humans, aging accompanied by impaired angiogenesis, diminished blood flow altered metabolism, among others. A cellular mechanism that impinges upon these manifestations of can be a suitable target for therapeutic intervention. Here we identify cell surface receptor CD47 as novel age-sensitive driver vascular metabolic dysfunction. With natural process, ligand...
Diabetes is a global public health burden and characterized clinically by relative or absolute insulin deficiency. Therapeutic agents that stimulate secretion improve sensitivity are in high demand as treatment options. CD47 cell surface glycoprotein implicated multiple cellular functions including recognition of self, angiogenesis, nitric oxide signaling; however, its role the regulation remains unknown. Here, we demonstrate receptor signaling inhibits release from human well mouse...
Vascular endothelial cells are continuously exposed to hemodynamic shear stress. Intensity and type of stress highly relevant vascular physiology pathology. Here, we modeled distribution in a tissue culture well (R = 17.5 mm, fill volume 2 ml) under orbital translation using computational fluid dynamics with the finite element method. Free surface distribution, wall stress, inclination angle, drag force, oscillatory index on bottom were modeled. Obtained results predict nonuniform during...
Abstract Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared a murine model IRI. The most effective agent was then...
MAGI1 is an intracellular adaptor protein that stabilizes cell junctions and regulates epithelial endothelial integrity. Here, we report in cells colocalizes with paxillin, β3-integrin, talin 1, tensin 3 α-4-actinin at mature focal adhesions actin stress fibers, their dynamics. Downregulation of reduces adhesion formation maturation, spreading, fiber RhoA/Rac1 activation. silencing increases phosphorylation paxillin Y118, indicator turnover. promotes integrin-dependent to ECM, invasion...
Pancreatic beta cells are highly susceptible to oxidative stress, which plays a crucial role in diabetes outcomes. Progress has been slow identify molecules that could be utilized enhance cell survival and function under stress. Itaconate, byproduct of the tricarboxylic acid cycle, both anti-inflammatory antioxidant properties. The effects itaconate on stress relatively unknown. We explored 4-octyl itaconate—a cell-permeable derivative itaconate—on MIN6 (a model) conditions caused by...
Acute kidney injury (AKI) initiates a complex pathophysiological cascade leading to epithelial cell death. Recent studies identify autophagy, key intracellular process that degrades cytoplasmic constituents, as protective against AKI. We have previously reported the protein thrombospondin‐1 and its receptor CD47 are induced in AKI; however, mechanism underlying their regulation of is unknown. Here, we investigated whether signaling affects autophagy regulate Wild‐type (WT) ‐/‐ mice were...
Abstract Expression of the downstream regulatory element antagonist modulator (DREAM) protein in dorsal root ganglia and spinal cord is related to endogenous control mechanisms acute chronic pain. In primary sensory trigeminal neurons, high levels DREAM are preferentially localized nucleus, suggesting a major transcriptional role. Here, we show that transgenic mice expressing dominant active mutant neurons increased responses following orofacial stimulation, which correlates with decreased...
Acute kidney injury (AKI) is a major health problem affecting millions of patients globally. There no effective treatment for AKI and new therapies are urgently needed. Novel drug development, testing progression to clinical trials overwhelmingly expensive. Drug repurposing more cost-effective measure. We identified 2 commonly used drugs (colchicine metformin) that alter inflammatory cell function signalling pathways characteristic AKI, tested them in models acute chronic assess therapeutic...
Acute kidney injury (AKI) remains an important source of progressive chronic injury. Loss renal blood flow with subsequent restoration, termed ischemia reperfusion (IR), is a common cause AKI. The cell surface receptor signal regulatory protein α (SIRP-α) expressed on macrophages and limits inflammation phagocytosis. SIRP-α has recently been found to have wider cell-based expression play role in IR. We explored this genetic model deficient signaling. Mice lacking cytoplasmic signaling...
Abstract FOXP3+ regulatory T cells (Tregs) are central to maintaining peripheral tolerance and immune homeostasis. They have the potential be developed as a cellular therapy treat various clinical ailments such autoimmune disorders, inflammatory diseases improve transplantation outcomes. However, major question remains whether Tregs can persist exert their function effectively in disease state, where broad spectrum of mediators could inactivate Tregs. In this study, we investigated...
The role of Regulatory T cells (Tregs) in tolerance induction post-transplantation is well-established, but Tregs adoptive transfer alone without combined immunosuppressants have failed so far achieving clinical outcomes. Here we applied a set well-designed criteria to test the influence commonly used (belatacept, tacrolimus, and mycophenolate) on cord blood-derived (CB-Tregs). Our study shows that while none these modulated stability expression homing molecules by CB-Tregs, belatacept met...
ABSTRACT Diabetes is a global public health burden and characterized clinically by relative or absolute insulin deficiency. Therapeutic agents that stimulate improve secretion sensitivity are in high demand as diabetic treatment. CD47 cell surface glycoprotein implicated multiple cellular functions, including recognition of self, angiogenesis, nitric oxide signaling, however its role the regulation remains unknown. For first time we demonstrate receptor signaling inhibits release from...
Skeletal muscle regeneration is a dynamic process driven by adult stem cells and their progeny. Mostly quiescent at steady state, become activated upon injury. Following activation, they proliferate, most of progeny differentiate to generate fusion-competent while the remaining self-renews replenish cell pool. While identity was defined more than decade ago, based on co-expression surface markers, myogenic progenitors were identified only recently using high-dimensional single-cell...