A5055560807- Neonatal and fetal brain pathology
- Neonatal Respiratory Health Research
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Peroxisome Proliferator-Activated Receptors
- Retinoids in leukemia and cellular processes
- Pregnancy and preeclampsia studies
- Fetal and Pediatric Neurological Disorders
- Neuroscience and Neuropharmacology Research
- Pelvic floor disorders treatments
- Reproductive tract infections research
- Neuroendocrine regulation and behavior
- Congenital Heart Disease Studies
- Retinal Development and Disorders
- Mitochondrial Function and Pathology
- Cardiovascular Disease and Adiposity
- RNA Research and Splicing
- RNA modifications and cancer
- Reproductive System and Pregnancy
- Coffee research and impacts
- Autoimmune Neurological Disorders and Treatments
- Lipid metabolism and biosynthesis
Children's Hospital of Philadelphia
2016-2024
California University of Pennsylvania
2023-2024
University of Pennsylvania
2008-2023
University of Maryland, Baltimore
2023
Child Neurology Associates
2023
Mount Sinai Hospital
2023
Universidade de Vigo
2008
Case Western Reserve University
2008
Peroxisome proliferator-activated receptor γ(PPARγ), a nuclear and the target of anti-diabetic thiazolinedione drugs, is known as master regulator adipocyte biology. Although it regulates hundreds genes, PPARγ binding to endogenous genes has rarely been demonstrated. Here, utilizing chromatin immunoprecipitation (ChIP) coupled with whole genome tiling arrays, we identified 5299 genomic regions in mouse 3T3-L1 adipocytes. The consensus PPARγ/RXRα “DR-1”-binding motif was found at most sites,...
Adipocyte differentiation is controlled by many transcription factors, but few known downstream targets of these factors are necessary for adipogenesis. Here we report that retinol saturase (RetSat), which an enzyme implicated in the generation dihydroretinoid metabolites, induced during adipogenesis and directly regulated factor peroxisome proliferator activated receptor gamma (PPARgamma). Ablation RetSat dramatically inhibited but, surprisingly, this block was not overcome putative product...
PurposeVariants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy males and females. We aimed to investigate sex-specific differences.MethodsWe collected the data of 37 unpublished patients (18 19 females) IQSEC2 pathogenic variants 5 individuals unknown significance reviewed published variants. compared variant types phenotypes females performed an analysis isoforms.ResultsIQSEC2 mainly led premature truncation were scattered throughout...
Autism spectrum disorders (ASDs) are characterized by a deficit in social communication, pathologic repetitive behaviors, restricted interests, and electroencephalogram (EEG) aberrations. While exhaustive analysis of nuclear DNA (nDNA) variation has revealed hundreds copy number variants (CNVs) loss-of-function (LOF) mutations, no unifying hypothesis as to the pathophysiology ASD yet emerged. Based on biochemical physiological analyses, it been hypothesized that may be result systemic...
Background We lack early biomarkers for predicting neurodevelopment (ND) outcomes in children with congenital heart disease (CHD). Placentas of fetuses CHD have abnormalities, including unbalanced fetal/placental weight ratios (F/P). Although DNA methylation profiles revealed insights into the maternal-fetal environment (MFE), it is unknown if correlates to normalized F/P ratio groups and how these differences relate ND outcomes. Methods prospectively recruited a cohort pregnant women...
Nuclear peroxisome proliferator-activated receptor-γ (PPARγ) is required for adipocyte differentiation, but its role in mature adipocytes less clear. Here, we report that knockdown of PPARγ expression 3T3-L1 returned the most genes to preadipocyte levels. Consistently, down-regulated not up-regulated showed strong enrichment binding. Surprisingly, all were reversed, and morphology was maintained an extended period after depletion. To explain this, focused on transcriptional regulators whose...
The identification of factors that define adipocyte precursor potential has important implications for obesity. Preadipocytes are fibroblastoid cells committed to becoming round lipid-laden adipocytes. In vitro, this differentiation process is facilitated by confluency, followed adipogenic stimuli. During adipogenesis, a large number cytostructural genes repressed before gene induction. Here we report the transcriptional repressor transcription factor 7-like 1 (TCF7L1) binds and directly...
Retinol saturase carries out a stereospecific saturation of the C13−C14 double bond all-trans-retinol to generate (13R)-all-trans-13,14-dihydroretinol. This compound is found in cells expressing mouse or zebrafish retinol and livers mice fed retinyl palmitate. All-trans-13,14-dihydroretinol oxidized vivo all-trans-13,14-dihydroretinoic acid, highly selective agonist retinoic acid receptor. The naturally occurring (13R)-all-trans-13,14-dihydroretinoic weaker than (13S) enantiomer, indicating...
Background Microtubules are dynamic polymers of α/β tubulin heterodimers that play a critical role in cerebral cortical development, by regulating neuronal migration, differentiation, and morphogenesis. Mutations genes encode either α- or β-tubulin spectrum proteins involved the regulation microtubule dynamics lead to clinically devastating malformations including lissencephaly. Methods This is single case report patient with lissencephaly, developmental delay, nystagmus, persistent...
The transcription factor Aristaless-related X-linked gene (Arx) is a monogenic in early onset epileptic encephalopathies (EOEEs) and fundamental regulator of stages brain development. However, Arx expression persists mature GABAergic neurons with an unknown role. To address this issue, we generated conditional knockout (CKO) mouse which postnatal was ablated parvalbumin interneurons (PVIs). Electroencephalogram (EEG) recordings CKO mice revealed increase theta oscillations the occurrence...
Intrauterine hypoxia is a common cause of brain injury in children resulting broad spectrum long-term neurodevelopmental sequela, including life-long disabilities that can occur even the absence severe neuroanatomic damage. Postnatal hypoxia-ischemia rodent models are commonly used to understand effects ischemia and transient on developing brain. models, however, have some limitations. First, they do not test impact placental pathologies outcomes from hypoxia. Second, primarily recapitulate...
Dysfunction in the parvalbumin (PV) subclass of GABAergic interneurons is implicated several neurodevelopmental disorders that evolve severity with postnatal developmental stages. Understanding molecular underpinnings changes function PV has been limited by difficulty isolation pure adult and high-quality RNA. Here, we describe our protocol for young preparation RNA from these cells. For complete details on use execution this protocol, please refer to Joseph et al. (2021).
Sex-specific differences in behavior have been observed anxiety and learning children exposed to prenatal inflammation; however, whether these behaviors manifest differently by age is unknown. This study assesses possible behavioral changes due utero inflammation as a function of neonatal, juvenile, adult animals presents potential molecular targets for differences. CD-1 timed pregnant dams were injected with lipopolysaccharide (LPS, 50 μg/animal) or saline at embryonic day 15. No stress...
Abstract The cervicovaginal microbiome is highly associated with women’s health microbial communities dominated by Lactobacillus spp. being considered optimal. Conversely, a lack of lactobacilli and high abundance strict facultative anaerobes including Gardnerella vaginalis , have been adverse reproductive outcomes. However, the molecular pathways modulated microbe interactions epithelia remain unclear. Using RNA-sequencing, we characterize in vitro epithelial transcriptional response to...
A 5-year-old girl presented with acute, rapidly progressive encephalopathy following minor head trauma and was found to have ocular dipping. Her secondary a channelopathy caused by CACNA1A mutation. This is the first reported case of dipping in an encephalopathic child CACNA1A-confirmed hemiplegic migraine. [J Pediatr Ophthalmol Strabismus. 2018;55:e4-e6.].
<title>Abstract</title> The cervicovaginal microbiome is highly associated with women's health, microbial communities dominated by <italic>Lactobacillus</italic> species considered optimal. Conversely, a lack of lactobacilli and high abundance strict facultative anaerobes, including <italic>Gardnerella vaginalis</italic>, have been adverse reproductive outcomes. However, how host-microbial interactions alter specific molecular pathways impact cervical vaginal epithelial function remains...
We report a 32-year-old G3P1 at 35 weeks 3 days with dichorionic, diamniotic twin gestation who presented for evaluation secondary to ventriculomegaly (VM) in one twin. Fetal ultrasound and MRI demonstrated microcephaly, severe VM, compression of the corpus callosum, scalp nuchal thickening, elongated ears, bilateral talipes, right-sided congenital diaphragmatic hernia (CDH), loss normal cerebral architecture, indicative prior insult affected The co-twin was grossly normal. family pursued...
When expanded prenatal genetic testing is recommended for patients with posterior fossa anomalies (PFAs), we seek to understand which tests would be most useful in making a diagnosis.