A5038571702- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Sirtuins and Resveratrol in Medicine
- Autophagy in Disease and Therapy
- Liver Disease Diagnosis and Treatment
- Nutrition and Health in Aging
- Diet and metabolism studies
- Child Nutrition and Water Access
- Immune Response and Inflammation
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Adipose Tissue and Metabolism
- Clinical Nutrition and Gastroenterology
- Digestive system and related health
- Diet, Metabolism, and Disease
- Chromatin Remodeling and Cancer
- Immune cells in cancer
- Drug Transport and Resistance Mechanisms
- Child Nutrition and Feeding Issues
- Metabolism and Genetic Disorders
- Neonatal Respiratory Health Research
- Neurofibromatosis and Schwannoma Cases
- Infant Nutrition and Health
- interferon and immune responses
- Pancreatic and Hepatic Oncology Research
Hospital for Sick Children
2016-2024
University of Toronto
2017-2024
SickKids Foundation
2016-2024
University College London
2020
Great Ormond Street Hospital
2020
McMaster Children's Hospital
2017
Tata Memorial Hospital
2017
Human Genome Sciences (United States)
2017
Purpose BRAF V600E is a potentially highly targetable mutation detected in subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group tumors remains unknown. Patients Methods A combined genetic institutional study patients with PLGGs long-term follow-up was performed (N = 510). Clinical treatment data mutated PLGG (n 99) were compared large international independent cohort mutated-PLGG 180). Results 69 405 (17%) across broad spectrum histologies...
Paediatric brain tumours arising in the thalamus present significant diagnostic and therapeutic challenges to physicians due their sensitive midline location. As such, genetic analysis for biomarkers aid diagnosis, prognosis treatment of these is needed. Here, we identified 64 thalamic gliomas with clinical follow-up characterized targeted genomic alterations using newly optimized droplet digital NanoString-based assays. The median age at diagnosis was 9.25 years (range, 0.63–17.55) survival...
Abstract Malnutrition impacts approximately 50 million children worldwide and is linked to 45% of global mortality in below the age five. Severe acute malnutrition (SAM) associated with intestinal barrier breakdown epithelial atrophy. Extracellular vesicles including exosomes (EVs; 30–150 nm) can travel distant target cells through biofluids milk. Since milk-derived EVs are known induce stem cell proliferation, this study aimed examine their potential efficacy improving malnutrition-induced...
The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- mTORC1-mediated autophagy mitochondrial homeostasis. Using a mouse organoid model SM, we studied repercussions these dysregulations on enteropathy protective capacity maintaining activity health.SM was induced through feeding male weanling C57BL/6 mice low...
Mortality in children with severe malnutrition is strongly related to signs of metabolic dysfunction, such as hypoglycemia. Lower circulating tryptophan levels suggest a possible disturbance the tryptophan-nicotinamide adenine dinucleotide (TRP-NAD+) pathway and subsequently NAD+ dependent metabolism regulator sirtuin1 (SIRT1). Here we show that weanling mice, induced by 2-weeks low protein diet feeding from weaning, leads an impaired TRP-NAD+ decreased affects hepatic mitochondrial turnover...
Previous studies identified recurrent fusion and duplication events in pediatric low-grade glioma (pLGG). In addition to their role diagnosis, the presence of these aid dictating therapy predicting patient survival. Clinically, BRAF alterations are most commonly using fluorescent situ hybridization (FISH). However, this method is costly, labor-intensive does not identify nonBRAF events. Here, we evaluated NanoString nCounter gene expression system for detecting 32 reported fusion/duplication...
Severe malnutrition is associated with infections, namely lower respiratory tract infections (LRTIs), diarrhea, and sepsis, underlies the high risk of morbidity mortality in children under 5 years age. Dysregulations neutrophil responses acute phase infection are speculated to underlie these severe adverse outcomes; however, very little known about their biology this context. Here, a lipopolysaccharide-challenged low-protein diet (LPD) mouse model, as model malnutrition, we show that protein...
Abstract Severe malnutrition accounts for half-a-million deaths annually in children under the age of five. Despite improved WHO guidelines, inpatient mortality remains high and is associated with metabolic dysfunction. Previous studies suggest a correlation between hepatic dysfunction impaired autophagy. We aimed to determine role mTORC1 inhibition murine model malnutrition-induced Wild type weanling C57/B6 mice were fed 18 or 1% protein diet two weeks. A third low-protein group received...
10509 Background: Pediatric low-grade gliomas (PLGG) are the most common CNS neoplasm in children. PLGG histologically and clinically diverse molecular stratification is desperately needed. BRAF-V600E mutations highly targetable for therapy but its biological relevance impact on outcome unknown. Methods: We determined RAS pathway other secondary all patients diagnosed with since 1985 (n = 854), 506 had sufficient tissue. Tumors were tested these alterations using QX200 Droplet Digital PCR...
Severe malnutrition is associated with life-threatening complications such as infections, namely lower respiratory tract infections (LRTI), diarrhea, and sepsis underlies the high risk of morbidity mortality in children under five years age. Dysregulations neutrophil responses acute phase infection, speculated to underlie these severe adverse outcomes; however very little known about their biology this context. Here a lipopolysaccharide (LPS)- challenged low protein diet (LPD) mouse model,...
To describe and compare liver mitochondrial peroxisomal histopathology by nutritional status in children who died following hospitalization for acute illness Malawi.
Background Malnutrition contributes to 45% of the death children under 5 years age. Mortality in severe malnutrition is often related metabolic disturbances, including hypoglycemia, indicating hepatic dysfunction. However, underlying pathophysiology poorly understood. Children with complicated have been found significantly lower circulating tryptophan levels their blood. Disturbances tryptophan‐nicotinamide pathway implicated liver and other organ diseases, potentially mediated by...
Malnutrition contributes to 45% of the deaths children < 5. Mortality in severe malnutrition is often related metabolic disturbances, including hypoglycemia, indicating hepatic dysfunction. Children with have been found significantly lower circulating tryptophan (TRP) levels their blood. Disturbances TRP-NAM pathway implicated liver and intestine diseases, potentially mediated by NAD-dependent deacetylase SIRT1. This study aim evaluate effect modulating on metabolism dysfunction a mouse...
Abstract Mortality in children with severe malnutrition is strongly related to signs of metabolic dysfunction, such as hypoglycemia. Lower circulating tryptophan levels suggest a possible disturbance the tryptophan-nicotinamide (TRP-NAM) pathway and subsequently NAD+ dependent metabolism regulator sirtuin1 (SIRT1). We report that weanling mice, induced by feeding low protein diet, leads an impaired TRP-NAM affects hepatic mitochondrial turnover function. demonstrate stimulating improves...