A5064600090- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- Hippo pathway signaling and YAP/TAZ
- Adipose Tissue and Metabolism
- Peptidase Inhibition and Analysis
- Alzheimer's disease research and treatments
- Neuropeptides and Animal Physiology
- Neuroblastoma Research and Treatments
- Glycosylation and Glycoproteins Research
- Protein Degradation and Inhibitors
- Drug Transport and Resistance Mechanisms
- Sirtuins and Resveratrol in Medicine
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Neurofibromatosis and Schwannoma Cases
- Advanced Chemical Sensor Technologies
- Neuroendocrine Tumor Research Advances
- Cancer, Hypoxia, and Metabolism
- Mass Spectrometry Techniques and Applications
- Adipokines, Inflammation, and Metabolic Diseases
- Advanced Glycation End Products research
- Graphene and Nanomaterials Applications
- Insect Pheromone Research and Control
- Neuroinflammation and Neurodegeneration Mechanisms
Queen's University
2016-2025
Kingston Health Sciences Centre
2023
Royal Hospital for Women
2020-2022
UNSW Sydney
2020
National Cancer Institute
2001-2019
National Institutes of Health
2001-2019
Merck & Co., Inc., Rahway, NJ, USA (United States)
2019
Takeda (United States)
2019
Carleton University
2013-2018
Freie Universität Berlin
2016
Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear that mediates the antidiabetic effects of thiazolidinediones. PPARγ present in adipose tissue and becomes elevated fatty livers, but roles specific tissues thiazolidinedione actions are unclear. We studied function liver both lipoatrophic A-ZIP/F-1 (AZIP) wild type mice. In AZIP mice, ablation reduced hepatic steatosis worsened hyperlipidemia, triglyceride clearance, muscle insulin resistance. Inactivation also abolished...
Disruption of the peroxisome proliferator-activated receptor γ (PPARγ) gene causes embryonic lethality due to placental dysfunction. To circumvent this, a PPARγ conditional knockout mouse was produced by using Cre-loxP system. The targeted allele, containing loxP sites flanking exon 2 gene, crossed into transgenic line expressing Cre recombinase under control alpha/beta interferon-inducible (MX) promoter. Induction MX promoter pIpC resulted in nearly complete deletion exon, corresponding...
Abstract Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated α (PPARα). Sustained activation of PPARα leads to development liver tumors in rats and mice. However, humans appear be resistant induction proliferation cancer by drugs. The molecular basis this species difference is not known. To examine mechanism determining differences proliferator response between mice humans, a PPARα-humanized mouse line was generated which human...
Abstract The Hippo pathway is a central regulator of tissue development and homeostasis, has been reported to have role during vascular development. Here we develop bioluminescence-based biosensor that monitors the activity core component LATS kinase. Using this library small molecule kinase inhibitors, perform screen for kinases modulating identify VEGFR as an upstream pathway. We find activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits activates effectors YAP TAZ....
The primary recognized health risk from common deficiencies in glucose-6-phosphate dehydrogenase (G6PD), a cytoprotective enzyme for oxidative stress, is red blood cell hemolysis. Here we show that litters untreated pregnant mutant mice with hereditary G6PD deficiency had increased prenatal (fetal resorptions) and postnatal death. When treated the anticonvulsant drug phenytoin, human teratogen commonly used women causes embryonic G6PD-deficient dams higher DNA oxidation more fetal death...
Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear superfamily, plays role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested influence carcinogen-induced colon cancer. Studies done vitro vivo also revealed that PPARγ ligands might promote differentiation and/or regression mammary tumors. To directly evaluate carcinogenesis, wild-type (+/+) or heterozygous (+/−) mice were administered 1 mg 7,12-dimethylbenz[...
The innate immune system modulates opioid-induced effects within the central nervous and one target that has received considerable attention is toll-like receptor 4 (TLR4). Here, we examined contribution of TLR4 in development morphine tolerance, hyperalgesia, physical dependence two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation Tlr4 gene rendering non-functional, B10ScNJ are null mutants. We found neither acute antinociceptive response to single dose...
Triple-negative breast cancers (TNBCs) account for ~25% of all invasive carcinomas and represent a large subset aggressive, high-grade tumors. Despite current research focused on understanding the genetic landscape TNBCs, reliable prognostic predictive biomarkers remain limited. Although dysregulated microRNAs (miRNAs) have emerged as key players in many cancer types, role miRNAs TNBC disease progression is unclear. We performed miRNA profiling 51 TNBCs by next-generation sequencing to...
Background:Peroxisome proliferator-activated receptor γ (PPARγ) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARγ expression in many cell types, including endothelial cells (ECs).
The results of recent studies using selective agonists for peroxisome proliferator-activated receptor β (PPARβ) suggest that this may have a role in regulating levels serum lipids animal models obesity and insulin resistance. To further examine possibility, lipid profiles mice lacking functional PPARβ were determined. PPARβ-null maintained on either normal chow or 10-week high fat (HF) diet, condition has been shown to induce resistance mice, elevated triglycerides primarily associated with...
Potential functional roles for the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skeletal muscle fatty acid catabolism and epithelial carcinogenesis have recently been described. Whereas PPARβ/δ is expressed liver, its function this tissue less clear. To determine role of chemically induced liver toxicity, wild-type PPARβ/δ-null mice were treated with azoxymethane (AOM) markers toxicity examined. Bile duct hyperplasia, regenerative increased serum alanine aminotransferase (ALT)...
Breast cancer is a leading cause of death in women worldwide. Active mutations PI3K catalytic subunit PIK3CA (e.g., H1047R) and amplification its homolog PIK3CB are observed large number breast cancers. In recent years, aberrant activation Transcriptional coactivator with PDZ binding motif (TAZ) paralog Yes-associated protein (YAP) have also been found to be important for development progression. However, whether interacts YAP/TAZ during mammary tumorigenesis unknown. Through systematic...
The Hippo pathway is an emerging signaling that plays important roles in organ size control, tissue homeostasis, tumorigenesis, metastasis, drug resistance, and immune response. Although many regulators of the have been reported, extracellular stimuli kinase remain largely unknown. To identify novel regulars pathway, this study we created first ultra-bright NanoLuc biosensor (BS) to monitor activity large tumor suppressor (LATS) 1, a central player pathway. We show BS achieves significantly...