- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Hormonal Regulation and Hypertension
- Signaling Pathways in Disease
- Regulation of Appetite and Obesity
- Endoplasmic Reticulum Stress and Disease
- Muscle Physiology and Disorders
- Cholesterol and Lipid Metabolism
- Estrogen and related hormone effects
- Genetic and Kidney Cyst Diseases
- Fuel Cells and Related Materials
- Cardiovascular Function and Risk Factors
- Hormonal and reproductive studies
- RNA modifications and cancer
- Vitamin D Research Studies
- Cardiac Fibrosis and Remodeling
- Health and Lifestyle Studies
- RNA Research and Splicing
- Congenital heart defects research
- Genetic Neurodegenerative Diseases
- Medical Imaging and Pathology Studies
- Glycogen Storage Diseases and Myoclonus
- Pediatric Pain Management Techniques
- FOXO transcription factor regulation
- Pregnancy and Medication Impact
Nationwide Children's Hospital
2024-2025
University of Edinburgh
2021-2025
Newcastle University
2023-2024
University of Newcastle Australia
2024
The Queen's Medical Research Institute
2021-2024
British Heart Foundation
2021-2024
Clinical Research Institute
2024
Centre for Life
2024
The University of Texas Southwestern Medical Center
2018-2021
Advanced Center for Chronic Diseases
2017-2019
Myocardium irreversibly injured by ischemic stress must be efficiently repaired to maintain tissue integrity and contractile performance. Macrophages play critical roles in this process. These cells transform across a spectrum of phenotypes accomplish diverse functions ranging from mediating the initial inflammatory responses that clear damaged subsequent reparative help rebuild replacement tissue. Although macrophage transformation is crucial myocardial repair, events governing are poorly...
The primary cilium is a singular cellular structure that extends from the surface of many cell types and plays crucial roles in vertebrate development, including heart. Whereas ciliated cells have been described developing heart, role for cilia adult heart has not reported. This, coupled with fact mutations genes coding multiple ciliary proteins underlie polycystic kidney disease, disorder numerous cardiovascular manifestations, prompted us to identify harboring determine whether play...
Heart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart and one for which no efficacious therapies exist. Obesity lipid mishandling greatly contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations perturbations in homeostasis HFpEF are largely unknown. Here, we report that cardiomyocyte steatosis coupled increases activity transcription factor FoxO1 (Forkhead box protein O1). depletion, as well over-expression Xbp1s (spliced...
Duchenne muscular dystrophy is a genetic disease produced by mutations in the dystrophin gene characterized early onset muscle weakness leading to severe and irreversible disability. The cellular molecular consequences of lack humans are only partially known, which crucial for development new therapies aiming slow or stop progression disease. Here we have analyzed quadriceps biopsies seven DMD patients aged 2 4 years old five age gender matched controls using single nuclei RNA sequencing...
Abstract Corticosteroid binding globulin (CBG; SERPINA6 ) binds >85% of circulating glucocorticoids but its influence on their metabolic actions is unproven. Targeted proteolytic cleavage CBG by neutrophil elastase (NE; ELANE significantly reduces affinity, potentially increasing ‘free’ glucocorticoid levels at sites inflammation. NE inhibited alpha-1-antitrypsin (AAT; SERPINA1 ). Using complementary approaches in mice and humans to manipulate or AAT, we show high-fat diet (HFD) increases...
Pain management following posterior spinal fusion (PSF) in pediatric patients can present significant challenges for clinicians. Opioids continue as the primary modality managing postoperative pain these patients, despite well-known concerns regarding their adverse effect profile such risk of dependence or abuse. Therefore, there has been increased focus on multimodal analgesic approaches that incorporate non-opioid medications, non-pharmacologic techniques, and regional anesthesia. Commonly...
Polycystin-1 (PC1) is a transmembrane protein originally identified in autosomal dominant polycystic kidney disease where it regulates the calcium-permeant cation channel polycystin-2. Autosomal patients develop renal failure, hypertension, left ventricular hypertrophy, and diastolic dysfunction, among other cardiovascular disorders. These individuals harbor PC1 loss-of-function mutations their cardiomyocytes, but functional consequences are unknown. ubiquitously expressed, its experimental...
Abstract Becker muscular dystrophy (BMD) is characterised by fiber loss and expansion of fibrotic adipose tissue. Several cells interact locally in what known as the degenerative niche. We analysed muscle biopsies controls BMD patients at early, moderate advanced stages progression using Hyperion imaging mass cytometry (IMC) labelling single sections with 17 markers identifying different components muscle. developed a software for analysing IMC images studied changes composition spatial...
The Food Based Dietary Guidelines (FBDG) are educational tools that help people to select appropriate foods for good nutrition and health.Most countries have FBDG's, but its dissemination implementation shown weaknesses.This paper presents the development process validation of 2012 FBDG Chilean population.The latest scientific evidence was reviewed new messages were validated with METAPLAN, a qualitative-quantitative method problem analysis applied information gathered 48 focus groups from...
Cardiac hypertrophy is an adaptive response triggered by pathological stimuli. Regulation of the synthesis and degradation Ca2+ channel inositol 1,4,5-trisphosphate receptor (IP3R) affects progression to cardiac hypertrophy. Herpud1, a component endoplasmic reticulum-associated (ERAD) complex, participates in IP3R1 signaling, but function Herpud1 remains unknown. We hypothesize that acts as negative regulator regulating IP3R protein levels. Our results show Herpud1-knockout mice exhibit...
The less affluent and educated members of the society tend to be prone healthy lifestyles.To describe feeding habits, nutrition, quality life working conditions construction workers comparing two recent surveys, namely 2009 Chilean National Health Survey (NHS) 2010 Work, Employment (WEH).One hundred ninety male aged 43±13 years were surveyed about habits during days weekends, smoking usual physical activity. Weight, height blood pressure also measured.In 2010, 82% overweight or obese...
Carbonyl reductase 1 (Cbr1), a recently discovered contributor to tissue glucocorticoid metabolism converting corticosterone 20β-dihydrocorticosterone (20β-DHB), is upregulated in adipose of obese humans and mice may contribute cardiometabolic complications obesity. This study tested the hypothesis that Cbr1-mediated influences mineralocorticoid receptor activation impacts glucose homeostasis lean states.
Glucocorticoids modulate glucose homeostasis, acting on metabolically active tissues such as liver, skeletal muscle, and adipose tissue. Intracellular regulation of glucocorticoid action in tissue impacts metabolic responses to obesity. ATP-binding cassette family C member 1 (ABCC1) is a transmembrane transporter known limit the accumulation exogenously administered corticosterone However, role ABCC1 endogenous its impact fuel metabolism has not been studied. Here, we investigate Abcc1...
Late-onset Pompe disease (LOPD) is a rare genetic disorder caused by the deficiency of acid alpha-glucosidase leading to progressive cellular dysfunction owing accumulation glycogen in lysosome. The mechanism relentless muscle damage (a classic manifestation disease) has been studied extensively analysing whole-muscle tissue; however, little, if anything, known about transcriptional heterogeneity among nuclei within multinucleated skeletal cells. This first report application single-nucleus...
The coronavirus disease 2019 (COVID-19) pandemic has led to a global surge in hospitalizations due pneumonia and respiratory distress. As with other infectious medical conditions, the perioperative care of patient an active or recent severe acute syndrome 2 (SARS-CoV-2) infection must address concerns regarding both healthcare providers patient. SARS-CoV-2-positive patients face higher risk pulmonary complications significantly rates mortality, especially those preoperative symptoms. We...