A5043094096- Cardiovascular Function and Risk Factors
- PARP inhibition in cancer therapy
- Pulmonary Hypertension Research and Treatments
- Erythropoietin and Anemia Treatment
- Adipose Tissue and Metabolism
- Protein Tyrosine Phosphatases
- Cardiac Imaging and Diagnostics
- Galectins and Cancer Biology
- Fuel Cells and Related Materials
- Heme Oxygenase-1 and Carbon Monoxide
- Muscle Physiology and Disorders
- Chronic Kidney Disease and Diabetes
- Peptidase Inhibition and Analysis
- Pluripotent Stem Cells Research
- Heart Rate Variability and Autonomic Control
- Renal Diseases and Glomerulopathies
- Cardiovascular and exercise physiology
- Hippo pathway signaling and YAP/TAZ
- Cardiac Arrest and Resuscitation
- Diet, Metabolism, and Disease
- Peroxisome Proliferator-Activated Receptors
- Cardiovascular Health and Disease Prevention
- Pancreatic function and diabetes
- Extracellular vesicles in disease
- Lipid metabolism and biosynthesis
University of Guelph
2013-2024
Saint John Regional Hospital
2015-2024
Sinai Health System
2022
McMaster University
2022
University of Toronto
2022
SUNY Upstate Medical University
2022
Lunenfeld-Tanenbaum Research Institute
2022
Platt College
2015
Podocytes are specialized epithelial cells of the kidney blood filtration barrier that contribute to permselectivity via a series interdigitating actin-rich foot processes. Positioned between adjacent projections is unique cell junction known as slit diaphragm, which physically connected actin cytoskeleton transmembrane protein nephrin. Evidence indicates tyrosine phosphorylation intracellular tail nephrin initiates signaling events, including recruitment cytoplasmic adaptor proteins Nck1...
Consumption of highly colored fruits and vegetables rich in anthocyanins has been associated with numerous health benefits. Purple carrots (PC) purple potatoes (PP) have higher anthocyanin concentrations biological activities compared less pigmented cultivars. We hypothesized that substitution the majority carbohydrate a high fat diet PP or PC, for 8 weeks, would improve insulin resistance hypertension, major components metabolic syndrome, orange (OC), white (WP) control, fat, sucrose-rich...
A growing proportion of heart failure patients present with impairments in both ventricles. Experimental pressure-overload (i.e., transverse aortic constriction, TAC) induces left ventricle (LV) hypertrophy and failure, as well right (RV) dysfunction. However, little is known about the coordinated progression biventricular dysfunction that occurs TAC. Here we investigated time course systolic diastolic function LV RV concurrently to improve our understanding chronology events Hemodynamic,...
Abstract Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and characterized craniofacial, growth, cognitive cardiac defects. NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which reproduced Raf1 L613V/+ knock-in mice. Here, using inducible L613V expression, we show that LVH results from the interplay of cell types. Cardiomyocyte enhances Ca 2+ sensitivity contractility without causing hypertrophy....
Myocardial infarction and reperfusion constitute a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival adaptation. Cell signalling, which is essential to cardiac development, also presents potential disease-modifying opportunities recover limit myocardial or maladaptive remodelling. Here, we hypothesized Yap signalling could be sensitive one more associated with early acute ischemia. We found Yap, not Taz, expression differed in...
Diaphragmatic weakness is a feature of heart failure (HF) associated with dyspnea and exertional fatigue. Most studies have focused on advanced stages HF, leaving the cause unresolved. The long-standing theory that pulmonary edema imposes mechanical stress, resulting in diaphragmatic remodeling, but stable HF patients rarely exhibit edema. We investigated how develops two mouse models pressure overload-induced HF. As patients, both had increased eupneic respiratory pressures ventilatory...
Dyspnea and reduced exercise capacity, caused, in part, by respiratory muscle dysfunction, are common symptoms patients with heart failure (HF). However, the etiology of diaphragmatic dysfunction has not been identified. To investigate effects HF on function, models were surgically induced CD-1 mice transverse aortic constriction (TAC) acute myocardial infarction (AMI), respectively. Assessment isolated strip myofilament force-pCa relationship, phosphorylation status proteins was performed...
Abstract Myocardial infarction and reperfusion is a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival adaptation. Cell signalling essential to cardiac development also presents potential disease-modifying opportunities recover limit myocardial or maladaptive remodelling. Here we hypothesized Yap could be sensitive one more associated with early acute ischemia. Yap, not Taz, expression differ in post-myocardial infarct compared...
Significance Statement Podocyte detachment is a major contributor to kidney disease progression, yet the mechanisms controlling podocyte adhesion are not well understood. We identified novel roles for Nck1 and Nck2 cytoskeletal adaptor proteins in cell through regulation of actin bundling at focal adhesions via α actinin-4. In vivo , loss and/or increases basement membrane matrix deposition renders podocytes more susceptible damage after injury with aging. More severe defects observed...
BACKGROUND Ventricular remodeling is a complex process involving cell death, inflammation, fibrosis, cardiomyocyte hypertrophy. Recent studies show that Hippo/YAP signaling regulates growth and survival following ischemic injury in the myocardium. However, its role ventricular still poorly understood may hold potential for therapeutic targeting. In this study, we investigated expression of proteins mouse model acute myocardial infarction. METHODS For infarction (AMI), mice were sedated with...
Erythropoietin (EPO) is widely recognized as the principle regulator of erythropoiesis, however, extra‐erythropoietic functions have been identified including cytoprotection, cardiac inotropy, cellular proliferation, and embryonic development. Whole body deletion either EPO or receptor lethal with impaired cardiogenesis leading to ventricular hypoplasia. While multiple extra‐renal tissue cell types produce EPO, whether heart a direct source remains unclear. Human recombinant increases...
Exercise intolerance, characterized by dyspnea and early onset of exertional fatigue, is a chief complaint among patients with heart failure (HF). Limb muscle dysfunction known contributor to exercise however, this phenomena does not explain dyspnea. Lung remodeling has been reported in end‐stage HF which could contribute underscoring the importance urgent need better understand its role HF. Our aim characterize development lung impact on intolerance We hypothesize that occurs HF, causing...
Myostatin, a negative regulator of skeletal muscle growth, is transcriptionally upregulated in the heart following myocardial infarction (MI). Investigations have largely focused on myostatin production left ventricle (LV) during development LV dysfunction. However, MI causes significant right (RV) dysfunction along with greater re‐expression fetal genes as compared to LV. Our objective was examine relative RV and expression MI. Methods. Mice were sacrificed infarct, peri‐infarct separated....
Assessment of cardiac function in patients with heart failure (HF) is generally limited to the evaluation systolic and diastolic left ventricle (LV). Right (RV) dysfunction considered a sequelae LV HF. However, pathogenesis RV remodeling has received little attention. Our objective was investigate progression following myocardial infarction (MI). Methods : Left right assessed using invasive hemodynamics, molecular histomorphometric approaches at 2, 4 9 18 weeks post‐MI induced by permanent...
A strong negative correlation between the size of a myocardial infarction (MI) and long‐term survival patient exists in clinical population. The current gold standard treatment for reducing infarct MI patients is acute reperfusion therapy (ART). Due to various contraindications, up 30 percent eligible do not receive ART. Thus, there an urgent need pharmacological alternatives this substantive As experiencing can only be treated after event precipitates symptoms, purpose study was establish...
Hypertrophic cardiomyopathy (HCM) has multiple etiologies, including hypertension, cardiac valve disease or genetic defects. Most inherited HCM results from defects in sarcomere proteins, but ~25% are caused by aberrant signal transduction genes. RASopathies developmental disorders with variably penetrant features, HCM, which mutations genes encoding RAS/extracellular signal-regulated kinase (ERK) pathway components. The most common RASopathy, Noonan Syndrome (NS), gain-of-function alleles...
Respiratory dysfunction is a prominent feature of heart failure (HF) but remains to be fully understood. Our objective was characterize diaphragmatic myopathy that manifests during the development HF. Methods HF induced in mice by transaortic constriction (TAC). Cardiorespiratory function measured vivo and diaphragm strips were used for histology vitro contractile at 2, 4 or 18 weeks TAC sham mice. Results In respiratory frequency pressure did not differ any time point anaesthetized animals...
Abstract Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and characterized craniofacial, growth, cognitive cardiac defects. NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which reproduced Raf1 L613V/+ knock-in mice. Here, using inducible L613V expression, we show that LVH results from the interplay of cell types. Cardiomyocyte enhances Ca 2+ sensitivity contractility without causing hypertrophy....
Background Cardiac output (CO) is a valuable measure of cardiac function, both clinically and in small animal models injury (e.g., myocardial infarction; MI). As the product stroke volume heart rate, CO can be estimated from volumes acquired one (i.e., M‐Mode) two single plane ellipsoid formula) dimensional echocardiographic images left ventricle (LV). Critically, deformations LV following MI non‐uniform composition/contractile properties) invalidate mathematical assumptions imperative to...