A5032438550- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Tissue Engineering and Regenerative Medicine
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Polyamine Metabolism and Applications
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- CAR-T cell therapy research
- Steroid Chemistry and Biochemistry
- Congenital heart defects research
- 14-3-3 protein interactions
- Cancer-related gene regulation
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Tryptophan and brain disorders
- Environmental DNA in Biodiversity Studies
- Gut microbiota and health
- Genomics and Phylogenetic Studies
- Genetics, Aging, and Longevity in Model Organisms
- Algal biology and biofuel production
- Pregnancy and preeclampsia studies
- Cardiovascular Function and Risk Factors
- Chromosomal and Genetic Variations
University of California, Los Angeles
2016-2025
University of Parma
2014-2024
QB3
2018-2023
UCLA Health
2017-2021
Broad Center
2017-2020
Quantitative BioSciences
2019-2020
Institute of Molecular and Cell Biology
2020
Alterations in the composition of intestinal microbiota have been correlated with aging and measures frailty elderly. However, relationships between microbial dynamics, age-related changes physiology, organismal health remain poorly understood. Here, we show that dysbiosis microbiota, characterized by an expansion Gammaproteobacteria, is tightly linked to age-onset barrier dysfunction Drosophila. Indeed, alterations precede predict onset aged flies. Changes occurring prior contribute...
Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed mammalian array, a single custom array that measures up to 36k CpGs per species well conserved across many species. We designed set probes can tolerate specific mutations. annotate in over 200 and report CpG island status chromatin states...
The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital disease. However, little known about how blood impacts formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high inhibits the maturation of cardiomyocytes genetic, structural, metabolic, electrophysiological, biomechanical levels by promoting nucleotide biosynthesis through pentose...
Methylation of cytosines (5(me)C) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves de novo methylation. In vivo mechanisms methylation establishment largely uncharacterized. Here, we use Saccharomyces cerevisiae as system lacking to define the chromatin features influencing activity murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 mutually exclusive co-localized with H3K36 methylated regions. support this...
Improvement in the performance of eukaryotic microalgae for biofuel and bioproduct production is largely dependent on characterization metabolic mechanisms within cell. The marine diatom Cyclotella cryptica, which was originally identified Aquatic Species Program, a promising strain large-scale bioproducts, such as omega-3 fatty acids. We sequenced nuclear genome methylome this oleaginous to identify genetic traits that enable substantial accumulation triacylglycerol. comprised highly...
Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis systemic complications COVID-19. Here, we create murine model SARS-CoV-2–induced severe toxicity and multiorgan involvement by expressing human ACE2 transgene in multiple tissues via viral delivery, followed administration SARS-CoV-2. The animals develop profound phenotype within 7 days weight loss, morbidity, failure to...
The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's (AD). Here, we show that FMD reduce cognitive decline AD pathology E4FAD 3xTg mouse models, with superior to those caused by protein restriction cycles. In mice, long-term hippocampal Aβ load hyperphosphorylated tau, enhance genesis neural stem cells, decrease microglia number, expression neuroinflammatory genes, including superoxide-generating NADPH oxidase...
Astrocytes are critical for the development and function of synapses. There notable species differences between human astrocytes commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic stable or exhibit dynamic changes associated with disease states age humans, which a barrier understanding astrocyte biology its potential involvement neurologic diseases. To better understand properties astrocytes, we acutely purified from cerebral cortices over 40 humans...
A genomic database of all Earth's eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction have information available. In 2018, scientists across the world united under Earth BioGenome Project (EBP), aiming produce high-quality reference genomes containing ~1.5 million recognized species. As European node EBP, Reference Genome Atlas (ERGA) sought implement new decentralised, equitable and inclusive model for producing genomes. For this, ERGA launched...
Maternal nutrient restriction causes the development of adult onset chronic diseases in intrauterine growth restricted (IUGR) fetus. Investigations mice have shown that either protein or calorie during pregnancy leads to glucose intolerance, increased fat mass, and hypercholesterolemia male offspring. Some these phenotypes are persist successive generations. The molecular mechanisms underlying IUGR remain unclear. placenta is a critical organ for mediating changes environment embryos. To...
Highlights•Fructose promotes transcriptomic and epigenomic reprogramming to perturb brain networks linking metabolism function.•The extracellular matrix genes Bgn Fmod emerge as key regulators of gene responsive fructose.•The omega-3 fatty acid DHA reverses fructose-induced genomic network reprogramming.Meng et al. report fructose a powerful inducer variability with the capacity reorganize critical for central metabolic regulation neuronal processes in brain; conversely, an acid, DHA, has...
The green alga Chlamydomonas reinhardtii undergoes gametogenesis and mating upon nitrogen starvation. While the steps involved in its sexual reproductive cycle have been extensively characterized, genome-wide transcriptional epigenetic changes underlying different life stages yet to be fully described. Here, we performed transcriptome methylome sequencing quantify expression DNA methylation from vegetative gametic cells of each type zygotes. We identified 361 genes with type-specific...
How artificial environmental cues are biologically integrated and transgenerationally inherited is still poorly understood. Here, we investigate the mechanisms of inheritance reproductive outcomes elicited by model chemical Bisphenol A in C. elegans. We show that (BPA) exposure causes derepression an epigenomically silenced transgene germline for 5 generations, regardless ancestral response. Chromatin immunoprecipitation sequencing (ChIP-seq), histone modification quantitation,...
Although analysis of maternal plasma cell-free content has been employed for screening genetic abnormalities within a pregnancy, limited attention paid to its use the detection adverse pregnancy outcomes (APOs) based on placental function. Here we investigated DNA and RNA 102 25 cord samples. Employing novel deconvolution methodology, found that during first trimester, placenta-specific increased prior subsequent development gestational diabetes with no change in patients preeclampsia while...
The advent of cell culture-based methods for the establishment and expansion human corneal endothelial cells (CEnC) has provided a source transplantable endothelium, with significant potential to challenge one donor-one recipient paradigm. However, concerns over identity remain, comprehensive characterization cultured CEnC across serial passages not been performed. To this end, we compared two established culture by assessing transcriptomic changes that occur during in vitro expansion. In...
Aging is associated with dramatic changes to DNA methylation (DNAm), although the causes and consequences of such alterations are unknown. Our ability experimentally uncover mechanisms epigenetic aging will be greatly enhanced by our study manipulate these using in vitro models. However, it remains unclear whether elicited cells culture can serve as a model what observed tissues vivo. To test this, we serially passaged mouse embryonic fibroblasts (MEFs) assessed DNAm at each time point via...
We investigated how an extremely transposon element (TE)-rich organism such as the plant-symbiotic ascomycete truffle Tuber melanosporum exploits DNA methylation to cope with more than 45,000 repeated elements that populate its genome.
Background Although curcumin's effect on head and neck cancer has been studied in vitro vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG‐157 a botanical drug containing multiple polyphenols, including curcumin, developed under US Food Drug Administration's Botanical Development, that delivers active components oromucosal tissues near tumor target. Methods A double‐blind, randomized, placebo‐controlled, phase 1 clinical trial...
TH17 cell subpopulations have been defined that contribute to inflammation and homeostasis, yet the characteristics of cells host defense against infection are not clear. To elucidate antimicrobial machinery subset, we studied response Cutibacterium acnes, a skin commensal is resistant IL-26, only known TH17-secreted protein with direct activity. We generated C. acnes–specific clones (AMTH17) varying activity which correlated by RNA sequencing expression transcripts encoding proteins...
In the eukaryotic cell, spliceosomes assemble onto pre-mRNA cotranscriptionally. Spliceosome assembly takes place in context of chromatin environment, suggesting that state may affect splicing. The molecular details and mechanisms through which affects splicing, however, are still unclear. Here, we show a role for histone methyltransferase Set2 its modification, H3K36 methylation, splicing high-throughput sequencing. Moreover, effect methylation on is mediated chromodomain protein Eaf3. We...
During canonical Wnt signaling, the receptor complex is sequestered together with glycogen synthase kinase 3 (GSK3) and Axin inside late endosomes, known as multivesicular bodies (MVBs). Here, we present experiments showing that causes endocytosis of focal adhesion (FA) proteins depletion Integrin β 1 (ITGβ1) from cell surface. FAs integrins link cytoskeleton to extracellular matrix. Wnt-induced caused ITGβ1 plasma membrane was accompanied by striking changes in actin cytoskeleton. In situ...