A5045575366- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Liver Disease Diagnosis and Treatment
- Cell death mechanisms and regulation
- Pancreatic function and diabetes
- Cytokine Signaling Pathways and Interactions
- Hippo pathway signaling and YAP/TAZ
- Immune Cell Function and Interaction
- Biomarkers in Disease Mechanisms
- PARP inhibition in cancer therapy
- Cell Adhesion Molecules Research
- Erythropoietin and Anemia Treatment
- Exercise and Physiological Responses
- Regulation of Appetite and Obesity
- Diabetes and associated disorders
- Growth Hormone and Insulin-like Growth Factors
- Adrenal and Paraganglionic Tumors
- Fungal Plant Pathogen Control
- Autophagy in Disease and Therapy
- Monoclonal and Polyclonal Antibodies Research
- Protein Kinase Regulation and GTPase Signaling
- Bone health and treatments
- Estrogen and related hormone effects
- Biochemical Analysis and Sensing Techniques
University of Toronto
2012-2023
St. Michael's Hospital
2022-2023
Unity Health Toronto
2022-2023
Diabetes Canada
2023
Toronto Public Health
2023
University Health Network
2013-2017
Toronto General Hospital
2012-2017
Toronto General Hospital Research Institute
2017
Institute of Medical Biology
2017
Health Net
2014
Abstract Reactive oxygen species (ROS) have been linked to a wide variety of pathologies, including obesity and diabetes, but ROS also act as endogenous signalling molecules, regulating numerous biological processes. DJ-1 is one the most evolutionarily conserved proteins across species, mutations in some cases Parkinson’s disease. Here we show that maintains cellular metabolic homeostasis via modulating levels murine skeletal muscles, revealing role maintaining efficient fuel utilization. We...
Focal adhesion kinase (FAK) acts as an adaptor at the focal contacts serving a junction between extracellular matrix and actin cytoskeleton. Actin dynamics is known determinant step in insulin secretion. Additionally, FAK has been shown to regulate signaling. To investigate essential physiological role of pancreatic β-cells vivo, we generated transgenic mouse model using rat promoter (RIP)-driven Cre-loxP recombination system specifically delete β-cells. These RIPcre(+)fak(fl/fl) mice...
Obesity-related insulin resistance is associated with an influx of pathogenic T cells into visceral adipose tissue (VAT), but the mechanisms regulating lymphocyte balance in such tissues are unknown. Here we describe important role for immune cytotoxic effector molecule perforin this process. Perforin-deficient mice (Prf1null) show early increased body weight and adiposity, glucose intolerance, when placed on high-fat diet (HFD). Regulatory effects tolerance mechanistically linked to control...
Abstract Focal adhesion kinase (FAK) plays a central role in integrin signalling, which regulates growth and survival of tumours. Here we show that FAK protein levels are increased adipose tissue insulin-resistant obese mice humans. Disruption adipocyte or 3T3 L1 cells decreases survival. Adipocyte-specific knockout display impaired expansion insulin resistance on prolonged metabolic stress from high-fat diet when crossed an db/db ob/ob genetic background. Treatment these with PPARγ agonist...
Abstract During obesity, macrophages can infiltrate metabolic tissues, and contribute to chronic low-grade inflammation, mediate insulin resistance diabetes. Recent studies have elucidated the role of JAK2, a key mediator downstream various cytokines growth factors. Our study addresses essential macrophage JAK2 in pathogenesis obesity-associated inflammation resistance. high-fat diet (HFD) feeding, macrophage-specific knockout (M-JAK2 −/− ) mice gained less body weight compared wildtype...
Caspases are cysteine-aspartic proteases that were initially discovered to play a role in apoptosis. However, caspase 8, particular, also has additional nonapoptotic roles, such as inflammation. Adipocyte cell death and inflammation hypothesized be initiating pathogenic factors type 2 diabetes. Here, we examined the pleiotropic of 8 adipocytes obesity-associated insulin resistance. Caspase expression was increased from mice humans with obesity Treatment 3T3-L1 inhibitor Z-IETD-FMK decreased...
Leptin has been shown to improve insulin sensitivity and glucose metabolism in obese diabetic ob/ob mice, yet the mechanisms remain poorly defined. We found that 2 d of leptin treatment improved fasting but not postprandial homeostasis, suggesting enhanced hepatic sensitivity. Consistent with this hypothesis, vivo receptor (IR) activation liver, skeletal muscle or fat. To explore cellular mechanism by which up-regulates IR activation, we examined expression protein tyrosine phosphatase...
Hepatocellular carcinoma is an end-stage complication of non-alcoholic fatty liver disease (NAFLD). Inflammation plays a critical role in the progression and development hepatocellular carcinoma. However, whether steatosis per se promotes cancer, molecular mechanisms that control this spectrum remain largely elusive. The Janus kinase signal transducers activators transcription (JAK-STAT) pathway mediates transduction by numerous cytokines regulate inflammation may contribute to...
The growing prevalence of obesity and diabetes necessitate a better understanding the role adipocyte biology in metabolism. Increasingly, erythropoietin (EPO) has been shown to have extraerythropoietic cytoprotective roles. Exogenous administration recently beneficial effects on mouse models EPO can modulate adipogenesis insulin signaling 3T3-L1 adipocytes. However, its physiological adipocytes not identified. Using male female mice with adipose tissue-specific knockdown receptor, we...
An aberrant increase in circulating catabolic hormone glucagon contributes to type 2 diabetes pathogenesis. However, mechanisms regulating secretion and α-cell mass are not well understood. In this study, we aimed demonstrate that phosphatidylinositol 3-kinase (PI3K) signaling is an important regulator of function. Mice with deletion PTEN, a negative pathway, α-cells show reduced levels attenuated l-arginine–stimulated both vivo vitro. This hypoglucagonemic state maintained after...
Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue signaling molecules that instigate propagate this disease remain unclear. The liver central site of inflammation lipid metabolism critical for atherosclerosis, JAK2 key mediator and, more recently, hepatic metabolism. However, precise effects Jak2 on atherosclerosis unknown. We show here deficiency in atherosclerosis-prone mouse models exhibited accelerated with increased plaque macrophages...
Adipose tissue is a very dynamic metabolic organ that plays an essential role in regulating whole-body glucose homeostasis. Dysfunctional adipose hypertrophy with obesity associated fibrosis and type 2 diabetes. Yes-associated protein 1 (YAP) transcription cofactor important the Hippo signaling pathway. However, of YAP homeostasis unknown.To study stress, we assessed how increased weight insulin resistance impact humans mouse models. To further investigate vivo specifically homeostasis,...
An outbreak of respiratory disease among thoroughbred horses in training Hong Kong was caused by equine herpesvirus 1 (EHV-1) subtype (abortion strain). Two the affected EHV-1 were serially blood sampled over a period several weeks and their haematological values measured. There an increase monocyte count first few days which steadily decreased one horse, but other had second peak after exercise, thus demonstrating importance not working animals early stages disease.