A5049602911- Epigenetics and DNA Methylation
- Birth, Development, and Health
- Folate and B Vitamins Research
- Pregnancy and preeclampsia studies
- Genetic Syndromes and Imprinting
- Reproductive Biology and Fertility
- Skin and Cellular Biology Research
- Renal and related cancers
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- Gestational Diabetes Research and Management
- Heat shock proteins research
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Sexual Differentiation and Disorders
- Intergenerational Family Dynamics and Caregiving
- Hair Growth and Disorders
- Hemoglobinopathies and Related Disorders
- Porphyrin Metabolism and Disorders
- Reproductive System and Pregnancy
- Cancer-related gene regulation
- Fibroblast Growth Factor Research
- Pluripotent Stem Cells Research
University of Cambridge
2012-2023
University of Calgary
2003-2013
Fetal growth is critically dependent on energy metabolism in the placenta, which drives active exchange of nutrients. Placental oxygen levels are therefore vital, and chronic hypoxia during pregnancy impairs fetal growth. Here we tested hypothesis that placental alters mitochondrial electron transport chain (ETS) function, sought to identify underlying mechanisms. We cultured human cells under different concentrations. Mitochondrial respiration was measured, alongside ETS complexes....
Abstract We recently reported the first evidence of placental endoplasmic reticulum (ER) stress in pathophysiology human intrauterine growth restriction. Here, we used a mouse model to investigate potential underlying mechanisms. Eif2s1 tm1RjK mice, which Ser51 eukaryotic initiation factor 2 subunit alpha (eIF2α) is mutated, display 30% increase basal translation. In placentas, observed increased ER and anomalous accumulation glycoproteins endocrine junctional zone (Jz), but not labyrinthine...
Defects in protein-folding and -degradation machinery have been identified as a major cause of intracellular protein aggregation aggregation-associated diseases. In general, it remains unclear how these aggregates are harmful to normal cellular function. We demonstrate here that,in the developing placenta mouse, absence Mrj (Dnajb6)co-chaperone prevents proteasome degradation keratin 18 (K18; Krt18)intermediate filaments, resulting formation inclusion bodies. These inclusions chorionic...
Endoplasmic reticulum (ER) stress promotes placental dysmorphogenesis and is associated with poor pregnancy outcomes. We show that unfolded protein response signalling pathways located in the ER drive differentiation of mouse trophoblast stem cells into subtypes involved development labyrinth zone invasion. In a model chronic (Eif2s1tm1RjK ), higher homozygous blastocysts accompanied by reduced trophectoderm cell number developmental delay also an increased incidence early loss....
Abstract Early placental development in mice involves patterning of the chorion into distinct layers, though little is understood regarding interactions that regulate its organization. Here we demonstrate keratin aggregates found Mrj −/− chorionic trophoblast cells are associated with abnormal cell morphology, collapse actin cytoskeleton, E‐cadherin and β‐catenin misexpression extracellular matrix (ECM) disorganization. Accordingly, vitro nonadherent display erratic migratory behavior. These...
Abstract The Mrj co‐chaperone is expressed throughout the mouse conceptus, yet its requirement for placental development has prohibited a full understanding of embryonic function. Here, we show that −/− embryos exhibit neural tube defects independent placenta phenotype, including exencephaly and thin‐walled tubes. Molecular analyses revealed fewer proliferating cells down‐regulation early progenitor ( Pax6 , Olig2 Hes5 ) neuronal Nscl2 SCG10 cell markers in neuroepithelial cells....
Folate (folic acid) deficiency and mutations in folate-related genes humans result megaloblastic anaemia. metabolism, which requires the enzyme methionine synthase reductase (MTRR), is necessary for DNA synthesis transmission of one-carbon methyl groups cellular methylation. In this study, we show that hypomorphic Mtrr
The mechanism behind transgenerational epigenetic inheritance is unclear, particularly through the maternal grandparental line. We previously showed that disruption of folate metabolism in mice by Mtrr hypomorphic mutation results congenital malformations. Either grandparent can initiate this phenomenon, which persists for at least four wildtype generations. Here, we use genome-wide approaches to reveal genetic stability model and differential DNA methylation germline mutant grandfathers....
Nonalcoholic fatty liver disease (NAFLD) is associated with dietary folate deficiency and mutations in genes required for one‑carbon metabolism. However, the mechanism through which this occurs unclear. To improve our understanding of link, we investigated morphology, metabolism fuel storage adult mice a hypomorphic mutation gene methionine synthase reductase (Mtrrgt). MTRR enzyme key regulator cycles. The Mtrrgt was previously shown to disrupt cause wide-spectrum developmental phenotypes...
The exposure to adverse environmental conditions (e.g. poor nutrition) may lead increased disease risk in an individual and their descendants. In some cases, the results be sexually dimorphic. A range of phenotypes has been associated with deficiency or defective metabolism vitamin folate. However, molecular mechanism linking folate development is still not well defined nor it clear whether are sex-specific. enzyme methionine synthase reductase (MTRR) required for progression utilization...