A5102785959- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Diabetes Management and Research
- Cancer Genomics and Diagnostics
- Diabetes and associated disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Pancreatic function and diabetes
- Immune cells in cancer
- MicroRNA in disease regulation
- Diabetes Treatment and Management
- Virus-based gene therapy research
- Zebrafish Biomedical Research Applications
- Mesenchymal stem cell research
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Tissue Engineering and Regenerative Medicine
- Vitamin C and Antioxidants Research
- Renin-Angiotensin System Studies
- Vitamin D Research Studies
- Stress Responses and Cortisol
- Coronary Artery Anomalies
- Menopause: Health Impacts and Treatments
University of Virginia
2019-2024
West Virginia University
2023
Monash University
2012-2021
La Trobe University
2018-2021
Princess Margaret Hospital for Children
2013-2018
The Kids Research Institute Australia
2016-2018
The University of Western Australia
2016-2018
Australian Regenerative Medicine Institute
2014-2018
The University of Queensland
2014
To determine the separate and combined effects of high-protein (HP) high-fat (HF) meals, with same carbohydrate content, on postprandial glycemia in children using intensive insulin therapy (IIT).Thirty-three subjects aged 8-17 years were given 4 test breakfasts amount but varying protein fat quantities: low (LF)/low (LP), LF/HP, HF/LP, HF/HP. LF HF meals contained g 35 fat. LP HP 5 40 protein. An individually standardized dose was for each meal. Postprandial assessed by 5-h continuous...
Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk mortality and age-related diseases in men, but the causal mechanistic relationships have yet to be established. Here, we show that male mice reconstituted bone marrow cells lacking display profibrotic pathologies including reduced cardiac function. Cardiac macrophages exhibited polarization toward a more fibrotic phenotype, treatment transforming growth factor β1-neutralizing antibody ameliorated dysfunction...
Clonal hematopoiesis of indeterminate potential is prevalent in elderly individuals and associated with increased risks all-cause mortality cardiovascular disease. However, mouse models to study the dynamics clonal its consequences on system under homeostatic conditions are lacking. We developed a model using adoptive transfer unfractionated ten-eleven translocation 2-mutant (Tet2-mutant) bone marrow cells into nonirradiated mice. Consistent age-related observed humans, these mice displayed...
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Background and Purpose— Experimental studies indicate that estrogen typically, but not universally, has a neuroprotective effect in stroke. Ischemic stroke increases membrane-bound G protein–coupled receptor (GPER) distribution expression the brain of male female mice. We hypothesized GPER activation may have greater males than females after Methods— Vehicle (dimethyl sulfoxide), agonist (G-1, 30 μg/kg), or antagonist (G-15, 300 μg/kg) were administered alone combination to young aged mice,...
Acute inflammation can exacerbate brain injury after ischemic stroke. Beyond its well-characterized role in calcium metabolism, it is becoming increasingly appreciated that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-VitD3), has potent immunomodulatory properties. Here, we aimed to determine whether 1,25-VitD3 supplementation could reduce subsequent and associated Male C57Bl6 mice were randomly assigned be administered either (100 ng/kg/day) or vehicle i.p. for 5 day prior...
Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, anti-inflammatory normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack ethical barriers to use could make these useful as a therapy in ischemic stroke.We tested efficacy acute (1.5 hours) or delayed (1-3 days) poststroke intravenous injection hAECs 4 established animal models cerebral ischemia. Animals included young (7-14 weeks) aged mice...
Stroke triggers a complex inflammatory process in which the balance between pro- and antiinflammatory mediators is critical for development of brain infarct. However, systemic changes may also occur parallel with inflammation. Here we demonstrate that administration recombinant IL-33, recently described member IL-1 superfamily cytokines, promotes Th2-type effects following focal ischemic stroke, resulting increased plasma levels cytokines fewer proinflammatory (3-nitrotyrosine+F4/80+)...
To compare systematically the impact of two novel insulin-dosing algorithms (the Pankowska Equation and Food Insulin Index) with carbohydrate counting on postprandial glucose excursions following a high fat protein meal.A randomized, crossover trial at Paediatric Diabetes centres was conducted. On each day, participants consumed or meal similar amounts. delivered according to counting, Index. Subjects fasted for 5 h test physical activity standardized. Postprandial glycaemia measured 300 min...
Abstract Background Intracerebral administration of the angiotensin II type 2 receptor (AT R) agonist, CGP42112, is neuroprotective in a rat model ischemic stroke. To explore further its possible cellular target(s) and therapeutic utility, we firstly examined whether CGP42112 may exert direct protective effects on primary neurons following glucose deprivation vitro . Secondly, tested effective when administered systemically mouse cerebral ischemia. Methods Primary cortical were cultured from...
Abstract Aim To quantify the insulin requirement for a high‐protein meal compared with low‐protein meal, controlling carbohydrate and fat content. Methods In this crossover study, young people Type 1 diabetes were randomized to consume high‐ (60 g) or (5 g), each containing 30 g 8 fat. A variation of clamp technique was used determine requirements maintain euglycaemia following 5 h. Results total 11 participants (mean ± sd age 16.5 2.7 years, HbA 1c 52 8.7 mmol/mol [6.9 0.8%], duration...
Functional modulation of the non-AT1R arm renin-angiotensin system, such as via AT2R activation, is known to improve stroke outcome. However, relevance Mas receptor, which along with forms protective a target in unclear. Here we tested efficacy selective MasR agonist, AVE0991, vitro and vivo models ischemic stroke. Primary cortical neurons were cultured from E15-17 mouse embryos for 7–9 d, subjected glucose deprivation 24 h alone or test drugs, percentage cell death was determined using...
Initial management of children diagnosed with type 1 diabetes (T1D) varies worldwide sparse high quality evidence regarding the impact different models care.To compare inpatient model care a hybrid home-based alternative, examining metabolic and psychosocial outcomes, knowledge, length stay, patient satisfaction.The study design was randomized-controlled trial. Inclusion criteria were: newly T1D, aged 3 to 16 years, living within approximately hour hospital, English-speaking, access...
Ischemic stroke is a major cause of mortality and long-term disability with limited treatment options, greater understanding the gene regulatory mechanisms underlying ischemic stroke-associated neuroinflammation required for new therapies. To study in vivo, mice were subjected to sustained ischemia by intraluminal filament-induced middle cerebral artery occlusion (MCAo) 24 h without reperfusion or transient 30 min followed 23.5 reperfusion, brain miRNA mRNA expression changes quantified...
Clonal hematopoiesis is a prevalent age-associated condition that results from the accumulation of somatic mutations in hematopoietic stem and progenitor cells (HSPCs). Mutations driver genes, confer cellular fitness, can lead to development expanding HSPC clones increasingly give rise progeny leukocytes harboring mutation. Because clonal has been associated with heart disease, stroke, mortality, experimental systems model these processes key understanding mechanisms underly this new risk...
Manipulating genes in hematopoietic stem cells using conventional transgenesis approaches can be time-consuming, expensive, and challenging. Benefiting from advances genome editing technology lentivirus-mediated transgene delivery systems, an efficient economical method is described here that establishes mice which are manipulated specifically cells. Lentiviruses used to transduce Cas9-expressing lineage-negative bone marrow with a guide RNA (gRNA) targeting specific red fluorescence...
Clonal hematopoiesis is a prevalent age-associated condition that results from the accumulation of somatic mutations in hematopoietic stem and progenitor cells (HSPCs). Mutations driver genes, confer cellular fitness, can lead to development expanding HSPC clones increasingly give rise progeny leukocytes harboring mutation. Because clonal has been associated with heart disease, stroke, mortality, experimental systems model these processes key understanding mechanisms underly this new risk...
Recent observational studies have reported that patients with low circulating levels of vitamin D experience larger infarct volumes and worse functional outcomes after ischemic stroke compared to those sufficient levels. However, it is unknown whether a causal relationship exists between poor outcome. This study aimed assess the effect deficiency on acute post-stroke. Male C57Bl6 mice (six week old) were assigned either control or deficient diet for four weeks prior stroke. Stroke was...