A5074863991- Epigenetics and DNA Methylation
- Birth, Development, and Health
- Animal Genetics and Reproduction
- Prenatal Substance Exposure Effects
- Genetic Syndromes and Imprinting
- Prenatal Screening and Diagnostics
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Reproductive Biology and Fertility
- Sperm and Testicular Function
- Pregnancy and preeclampsia studies
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- RNA Interference and Gene Delivery
- Air Quality and Health Impacts
- Virus-based gene therapy research
- Molecular Biology Techniques and Applications
- Cancer-related gene regulation
- Adipose Tissue and Metabolism
- Energy and Environment Impacts
- RNA Research and Splicing
- Climate Change and Health Impacts
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Gestational Diabetes Research and Management
Texas A&M University
2016-2025
Children's Hospital Research Institute of Manitoba
2023
Mitchell Institute
2023
Texas A&M Health Science Center
2016
Universidad de Las Palmas de Gran Canaria
2014
Roswell Park Comprehensive Cancer Center
2014
Lawson Health Research Institute
2011
Western University
2007-2011
Children’s Health Research Institute
2010-2011
Cold Spring Harbor Laboratory
2005-2008
By virtue of their accumulated genetic alterations, tumor cells may acquire vulnerabilities that create opportunities for therapeutic intervention. We have devised a massively parallel strategy screening short hairpin RNA (shRNA) collections stable loss-of-function phenotypes. assayed from 6000 to 20,000 shRNAs simultaneously identify genes important the proliferation and survival five cell lines derived human mammary tissue. Lethal common these targeted many known cell-cycle regulatory...
Polarized activation of adipose tissue macrophages (ATMs) is crucial for maintaining function and mediating obesity-associated cardiovascular risk metabolic abnormalities; however, the regulatory network this key process not well defined. Here, we identified a PPARγ/microRNA-223 (miR-223) axis that controls macrophage polarization by targeting distinct downstream genes to shift cellular response various stimuli. In BM-derived macrophages, PPARγ directly enhanced miR-223 expression upon...
Significance Particulate matter exposure causes infant respiratory morbidity and mortality, but the role of ultrafine particles (UFPs) with an aerodynamic diameter less than 0.1 μm in asthma tract infections is unclear. Limited mechanistic information available concerning UFP influence on etiology childhood or susceptibility to infections. Here we exposed two strains mice (sensitive oxidative stress allergen exposure) UFPs throughout gestation at concentrations relevant human exposures. Our...
Given the difficulty of applying gene knockout technology to species other than mice, we decided explore utility RNA interference (RNAi) in silencing expression genes livestock. Short hairpin RNAs (shRNAs) were designed and screened for their ability suppress caprine bovine prion protein (PrP). Lentiviral vectors used deliver a transgene expressing GFP an shRNA targeting PrP into goat fibroblasts. These cells then nuclear transplantation produce cloned fetus, which was surgically recovered...
Isolation and culture of both embryonic tissue specific stem cells provide an enormous opportunity to study the molecular processes driving development. To gain insight into initial events underpinning mammalian embryogenesis, pluripotent from each three distinct lineages present within preimplantation blastocyst have been derived. Embryonic (ES), trophectoderm (TS) extraembryonic endoderm (XEN) possess developmental potential their founding seemingly utilize epigenetic modalities program...
Abstract Adipose tissue resident B cells account for more than 20% of stromal within visceral adipose tissues; however, their functions in the niche are poorly elucidated. Here we report that miR-150 modulates function by controlling activation and interactions with other immune cells. miR-150KO mice displayed exacerbated obesity-associated inflammation systemic insulin resistance, which is recapitulated adoptive transfer cells, but not purified immunoglobulin, into obese null mice. Using...
In recent years, we have come to recognize that a multitude of in utero exposures the capacity induce development congenital and metabolic defects. As most these encounters manifest their effects beyond window exposure, deciphering mechanisms teratogenesis is incredibly difficult. For many agents, altered epigenetic programming has become suspect transmitting lasting signature exposure leading dysgenesis. However, while several chemicals can perturb chromatin structure acutely, for agents...
Although clinical data support an association between paternal alcohol use and deficits in child neurocognitive development, the relationship drinking alcohol-induced growth phenotypes remains challenging to define. Using established mouse model of chronic exposure, previous work by our group has linked preconception sex-specific patterns fetal restriction placental dysfunction. The aim present study was investigate long-term impact on offspring metabolic programming. Preconception exposure...
Background From studies using a diverse range of model organisms, we now acknowledge that epigenetic changes to chromatin structure provide plausible link between environmental teratogens and alterations in gene expression leading disease. Observations from number independent laboratories indicate ethanol (EtOH) has the capacity act as powerful disruptor potentially derail coordinated processes cellular differentiation. In this study, sought examine whether primary neurospheres cultured...
SUMMARY Somatic‐cell nuclear transfer (SCNT) experiments have paved the way to field of cellular reprogramming. The demonstrated ability clone over 20 different species date has proven that technology is robust but very inefficient, and prone developmental anomalies. Yet, offspring from cloned animals exhibit none abnormalities their parents, suggesting low efficiency high mortality are epigenetic in origin. barriers reprogramming somatic cells into a totipotent embryo capable developing...
To understand the complex regulation of genomic imprinting it is important to determine how early embryos establish imprinted gene expression across large chromosomal domains. Long non-coding RNAs (ncRNAs) have been associated with domains, yet their function remains undefined. Here, we investigated mouse Kcnq1ot1 ncRNA and its role in during preimplantation development by utilizing embryonic extra-embryonic stem cell models. Our findings demonstrate that extends 471 kb from transcription...
The preconception environment is a significant modifier of dysgenesis and the development environmentally-induced disease. To date, fetal alcohol spectrum disorders (FASDs) have been exclusively associated with maternal exposures, yet emerging evidence suggests male-inherited alterations in developmental program sperm may be relevant to growth-restriction phenotypes this condition. Using mouse model voluntary consumption, we find chronic male ethanol exposure associates growth restriction,...
Abstract Using a mouse model, studies by our group reveal that paternal preconception alcohol intake affects offspring fetal-placental growth, with long-lasting consequences on adult metabolism. Here, we tested the hypothesis chronic male exposure impacts histone enrichment in sperm and these changes are associated altered developmental programming placenta. chromatin immunoprecipitation, find alcohol-induced increases H3 lysine 4 trimethylation (H3K4me3) map to promoters presumptive...
Preconception paternal ethanol exposures
Abstract In studies of somatic cell nuclear transfer (SCNT), the ability factors within oocyte to epigenetically reprogram transferred nuclei is essential for embryonic development clone proceed. However, irregular patterns X‐chromosome inactivation, abnormal expression imprinted genes, and genomic DNA hypermethylation are frequently observed in reconstructed embryos, suggesting abnormalities this process. To better understand epigenetic events underlying SCNT reprogramming, we sought...
Epigenetic mechanisms of paternal inheritance are an emerging area interest in our efforts to understand fetal alcohol spectrum disorders. In rodent models examining maternal exposures, different genetic backgrounds protect or sensitize offspring alcohol-induced teratogenesis. However, whether background can mitigate sperm-inherited alterations developmental programming and modify the penetrance growth defects induced by preconception exposures remains unaddressed. previous studies pure...
Hormesis refers to graded adaptive responses harmful environmental stimuli where low-level toxicant exposures stimulate tissue growth and responsiveness while, in contrast, higher-level induce toxicity. Although the intergenerational inheritance of programmed hormetic is described plants insects, researchers have yet observe this phenomenon mammals. Using a physiologically relevant mouse model, we demonstrate that chronic preconception paternal alcohol program nonlinear, dose-dependent...