A5021741859- Genetic Syndromes and Imprinting
- Microbial Natural Products and Biosynthesis
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Genetic and Kidney Cyst Diseases
- Plant Disease Resistance and Genetics
- Plant-Microbe Interactions and Immunity
- Regulation of Appetite and Obesity
- Bacteriophages and microbial interactions
- Pancreatic function and diabetes
- Quinazolinone synthesis and applications
- Digestive system and related health
- Cancer-related molecular mechanisms research
- Biochemical Analysis and Sensing Techniques
- Hedgehog Signaling Pathway Studies
- Adipose Tissue and Metabolism
- Bioactive Compounds and Antitumor Agents
- Sperm and Testicular Function
- Biochemical and Molecular Research
- Cellular transport and secretion
- Antibiotic Resistance in Bacteria
- Breastfeeding Practices and Influences
- Birth, Development, and Health
- Invertebrate Immune Response Mechanisms
Columbia University Irving Medical Center
2018-2023
Columbia University
2008-2023
Pediatrics and Genetics
2021
Royal College of Physicians
2021
University of Leicester
2002-2004
Two recent, large whole-genome association studies (GWAS) in European populations have associated a ∼47-kb region that contains part of the FTO gene with high body mass index (BMI). The functions and adjacent FTM human biology are not clear. We examined expression these genes organs mice segregating for monogenic obesity mutations, exposed to underfeeding/overfeeding, 4°C. Fto/ Ftm was reduced mesenteric adipose tissue A y , Lep ob Lepr db Cpe fat or tub there similar trend other tissues....
The first intron of FTO contains common single nucleotide polymorphisms associated with body weight and adiposity in humans. In an effort to identify the molecular basis for this association, we discovered that RPGRIP1L (a ciliary gene located close proximity transcriptional start site FTO) are regulated by isoforms P200 P110 transcription factor, CUX1. This regulation occurs via a AATAAATA regulatory (conserved mouse) within intronic region Single polymorphism rs8050136 (located site)...
Noncoding polymorphisms in the fat mass and obesity-associated (FTO) gene represent common alleles that are strongly associated with effects on food intake adiposity humans. Previous studies have suggested obesity-risk allele rs8050136 first intron of FTO alters a regulatory element recognized by transcription factor CUX1, thereby leading to decreased expression retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Here, we evaluated another potential CUX1 rs1421085...
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder caused by mutations in genes encoding components of the primary cilium and characterized hyperphagic obesity. To investigate molecular basis obesity human BBS, we developed cellular model BBS using induced pluripotent stem cell-derived (iPSC-derived) hypothalamic arcuate-like neurons. BBS1M390R BBS10C91fsX95 did not affect neuronal differentiation efficiency but morphological defects, including impaired neurite outgrowth...
<h3>Objective</h3> To investigate the potential association of plastin 3 (<i>PLS3</i>) expression levels in blood with disease severity spinal muscular atrophy (SMA). <h3>Design</h3> Measurement of<i>PLS3</i>messenger RNA patients types I, II, and III SMA. <h3>Setting</h3> Pediatric Neuromuscular Clinical Research Network SMA Natural History study. <h3>Participants</h3> A cohort 88 both sexes who had <h3>Main Outcome Measures</h3> Levels relation to type and<i>SMN2</i>copy number....
Intronic polymorphisms in the α-ketoglutarate–dependent dioxygenase gene (FTO) that are highly associated with increased body weight have been implicated transcriptional control of a nearby ciliary gene, retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Previous studies shown congenital Rpgrip1l hypomorphism murine proopiomelanocortin (Pomc) neurons causes obesity by increasing food intake. Here, we show and adult-onset deletion Pomc-expressing hyperphagia likely...
Summary The tylosin biosynthetic gene cluster of Streptomyces fradiae is remarkable in harbouring at least five regulatory genes, two which ( tylS and tylT ) encode proteins the antibiotic protein (SARP) family. aim present work was to assess respective contributions TylS TylT production. A combination targeted disruption, fermentation studies expression analysis via reverse transcriptase–polymerase chain reaction (RT–PCR) suggests that essential for production controls tylR (previously...
Summary During promoter‐probe analysis carried out in Streptomyces lividans , the TylP protein powerfully inhibited reporter gene expression from tylP promoter, raising likelihood that is autoregulated its native host, fradiae . Also S. negatively controlled tylQ even though could still be switched off strains specifically disrupted Under latter conditions, tylosin production was brought forward and enhanced, whereas overexpression of re‐sulted reduced levels antibiotic, accompanied by...
Summary Control of tylosin production in Streptomyces fradiae features interplay between a repressor, TylQ, and an activator, TylS, during regulation tylR . The latter encodes pathway‐specific activator that controls most the tylosin‐biosynthetic ( tyl ) genes are subject to regulation. This was established by targeted gene disruption applied separately tylS together with transcript analysis involving reverse transcription polymerase chain reaction (RT‐PCR). TylR multiple encode synthesis or...
SNPs in the first intron of α-ketoglutarate-dependent dioxygenase (FTO) convey effects on adiposity by mechanisms that remain unclear, but appear to include modulation expression FTO itself, as well other genes cis. is lower fibroblasts and iPSC-derived neurons individuals segregating for obesity risk alleles. We employed vitro adipogenesis models investigate molecular which Fto affects adipocyte development function. was upregulated during adipogenesis, required maintenance CEBPB...
Congenital lipoid adrenal hyperplasia (CLAH), caused by mutations in steroidogenic acute regulatory protein (StAR), is most frequent Japanese and Palestinians. We report eight Palestinians from four unrelated families with CLAH.The objective of the study was to identify mutation(s) StAR, correlate genotype phenotype, determine whether common mutation represents a founder mutation.Clinical, histopathological, molecular genetic characterization performed these patients.All affected individuals...
Perturbations in the functional integrity of leptin axis are obvious candidates for mediation altered adiposity. In a large number genetic association studies humans, nonconservative LEPR Q223R allele has been inconsistently associated with Subtle, long‐term effects such variants can be obscured by environment and other confounders that render definitive inferences difficult to reach. We directly assessed biological this variant 129P3/J mice segregating humanized Lepr at codon 223. No were...
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) has become the tool of choice for genome editing. Despite fact that it evolved as a highly efficient means to edit/replace coding sequence, CRISPR/Cas9 efficiency "clean" editing non-coding DNA remains low. We set out introduce single base-pair substitution in two intronic SNPs at FTO locus without altering nearby sequence. Substitution increased up 10-fold by treatment human embryonic stem...
Genetic variants within the FTO (α-ketoglutarate-dependent dioxygenase) gene have been strongly associated with a modest increase in adiposity as result of increased food intake. These risk alleles are decreased expression both and neighboring RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein 1 like). encodes that is critical to function primary cilium, which conveys extracellular information cell. Rpgrip1l+/− mice exhibit adiposity, part, hyperphagia. Here, we describe...
Energy balance is controlled by interconnected brain regions in the hypothalamus, brainstem, cortex, and limbic system. Gene expression signatures of these can help elucidate pathophysiology underlying obesity. RNA sequencing was conducted on P56 C57BL/6NTac male mice E14.5 embryo punch biopsies 16 obesity-relevant regions. The 190 known obesity-associated genes (monogenic, rare, low-frequency coding variants; GWAS; syndromic) analyzed each anatomical region. Genes associated with genetic...
Background Lowe syndrome (LS) is an X linked disease caused by pathogenic variants in the OCRL gene that impacts approximately 1 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy. Methods This study a retrospective review of clinical reported family based survey conducted Syndrome Association. Frequency non-ocular feature(s) LS their age onset was summarised. An LS-specific therapy effectiveness scale used to assess...
SNPs in the first intron of fat mass and obesity-associated (FTO) gene represent strongest genome-wide associations with adiposity [body index (BMI)]; molecular basis for these is under intense investigation. In European populations, focus most association studies conducted to date, single nucleotide polymorphisms (SNPs) have indistinguishable due high level linkage disequilibrium (LD). However, African American (AA) individuals, reduced LD increased haplotype diversity permit finer...