A5101740328- RNA Research and Splicing
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Drug-Induced Hepatotoxicity and Protection
- RNA and protein synthesis mechanisms
- Spectroscopy Techniques in Biomedical and Chemical Research
- Computational Drug Discovery Methods
- HIV/AIDS drug development and treatment
- Erythropoietin and Anemia Treatment
- Cancer-related gene regulation
- Receptor Mechanisms and Signaling
- Gene Regulatory Network Analysis
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Pharmacological Effects and Toxicity Studies
- Statistical Methods in Clinical Trials
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Retinal Development and Disorders
- Cancer, Hypoxia, and Metabolism
Stanford University
2022-2024
Sun Yat-sen University
2012-2024
Providence College
2024
GlaxoSmithKline (United States)
2013-2023
Janssen (United States)
2014-2020
Vertex Pharmaceuticals (United States)
2017-2020
Pfizer (United States)
2017-2020
Corning (United States)
2017-2020
Novartis (United States)
2017-2020
Eisai (United States)
2017-2020
<h2>Summary</h2> Enhancer clusters overlapping disease-associated mutations in Pierre Robin sequence (PRS) patients regulate <i>SOX9</i> expression at genomic distances over 1.25 Mb. We applied optical reconstruction of chromatin architecture (ORCA) imaging to trace 3D locus topology during PRS-enhancer activation. observed pronounced changes between cell types. Subsequent analysis single-chromatin fiber traces revealed that these ensemble-average differences arise through the frequency...
Fusion of cytotrophoblasts into the multinucleated syncytiotrophoblast layer is essential for development a functional placenta. The envelope protein human endogenous retrovirus W (HERV-W) family member, syncytin 1, has been shown to mediate placental cell fusion. Recently, another HERV member (HERV-FRD), 2, identified and be highly expressed in To better understand biology this study we first investigated 2 gene expression normal preeclamptic placentas then characterized functions 2. was...
Drug-induced liver injury is the most common cause of market withdrawal pharmaceuticals, and thus, there considerable need for better prediction models DILI early in drug discovery. We present a study involving 223 marketed drugs (51% associated with clinical hepatotoxicity; 49% non-hepatotoxic) to assess concordance vitro bioactivation data hepatotoxicity have used these develop decision tree help reduce late-stage candidate attrition. Data P450 metabolism-dependent inhibition (MDI) all...
The HUSH complex recognizes and silences foreign DNA such as viruses, transposons, transgenes without prior exposure to its targets. Here, we show that endogenous targets of the fall into two distinct classes based on presence or absence H3K9me3. These are further distinguished by their transposon content differential response loss HUSH. A de novo genomic rearrangement at Sox2 locus induces a switch from H3K9me3-independent H3K9me3-associated targeting, resulting in silencing. We demonstrate...
Secondary and tertiary alicyclic amines are widely found in pharmaceuticals environmental compounds. The formation of iminium ions as reactive intermediates the metabolic activation has previously been investigated radiometric assays where radiolabeled cyanide is typically employed. In this paper, we report a relatively high throughput LC-MS/MS method for detection nonradiolabeled adduct formed rat or human liver microsomal incubations via constant neutral loss scan followed by structural...
Syncytin 2 is a newly identified placental membrane protein with fusogenic and immunosuppressive activities. Major facilitator superfamily domain containing 2A (MFSD2A) the cognate receptor for syncytin 2-mediated cell-cell fusion. Both MFSD2A are highly expressed in placenta. In this study to understand regulation of expression placenta, we found that gene epigenetically silenced nonplacental cells by cytosine-phosphate-guanine (CpG) dinucleotide methylation genes regulated transcription...
Increasing amounts of genes have been shown to utilize alternative polyadenylation (APA) 3′-processing sites depending on the cell and tissue type and/or physiological pathological conditions at time processing, construction genome-wide database regarding APA is urgently needed for better understanding poly(A) site selection APA-directed gene expression regulation a given biology. Here we present web-accessible database, named APASdb (http://mosas.sysu.edu.cn/utr), which can visualize...
PET imaging with radiolabeled drugs provides information on tumor uptake and dose-dependent target interaction to support selection of an optimal dose for future efficacy testing. In this immuno-PET study the anti–human epidermal growth factor receptor (HER3) mAb GSK2849330, we investigated biodistribution <sup>89</sup>Zr-labeled GSK2849330 evaluated engagement as a function antibody mass dose. <b>Methods:</b><sup>89</sup>Zr-GSK2849330 distribution was monitored in 6 patients HER3-positive...
Tandem 3′ untranslated regions (UTRs), produced by alternative polyadenylation (APA) in the terminal exon of a gene, could have critical roles regulating gene networks. Here we profiled tandem poly(A) events on genome-wide scale during embryonic development zebrafish ( Danio rerio ) using recently developed SAPAS method. We showed that 43% expressed protein-coding genes UTRs. The average UTR length follows V-shaped dynamic pattern early embryogenesis, which UTRs are first shortened at...
The Innovation and Quality Induction Working Group presents an assessment of best practice for data interpretation in vitro induction, specifically, response thresholds, variability, application controls, translation to clinical risk with focus on CYP3A4 mRNA. Single concentration control Emax/EC50 prototypical inducers were compiled from many human hepatocyte donors different laboratories. Clinical CYP3A induction gathered 51 compounds, 16 which proprietary. A large degree variability was...
Single-molecule RNA fluorescence in situ hybridization (smFISH) provides unparalleled resolution the measurement of abundance and localization nascent mature transcripts fixed, single cells. We developed a computational pipeline (BayFish) to infer kinetic parameters gene expression from smFISH data at multiple time points after induction. Given an underlying model expression, BayFish uses Monte Carlo method estimate Bayesian posterior probability quantify parameter uncertainty given observed...
Abstract The N-nitrosamine, N-nitrosodimethylamine (NDMA), is an environmental mutagen and rodent carcinogen. Small levels of NDMA have been identified as impurity in some commonly used drugs, resulting several product recalls. In this study, was evaluated OECD TG-488 compliant Muta™Mouse gene mutation assay (28-day oral dosing across seven daily doses 0.02-4 mg/kg/day) using integrated design that assessed at the transgenic lacZ locus various tissues endogenous Pig-a gene-locus, along with...
Although critical for tuning the timing and level of transcription, enhancer communication with distal promoters is not well understood. Here, we bypass need sequence-specific transcription factors (TFs) recruit activators directly using a chimeric array gRNA oligos to target dCas9 fused activator VP64-p65-Rta (CARGO-VPR). We show that this approach achieves effective recruitment arbitrary genomic sites, even those inaccessible when targeted single guide. utilize CARGO-VPR across Prdm8-Fgf5...
A key feature of the CNS is structural plasticity, ability neurons to alter their morphology and connectivity in response sensory experience other changes environment. How this plasticity achieved at molecular level not well understood. We provide evidence that simultaneously trigger multiple signaling pathways either promote or restrict growth dendritic arbor; through a balance these opposing signals. Specifically, we have uncovered novel, activity-dependent pathway restricts arborization....
Rosuvastatin is a widely prescribed antihyperlipidemic which undergoes limited metabolism, but an in vitro substrate of multiple transporters [organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP1A2, OATP2B1, sodium-taurocholate cotransporting polypeptide, breast cancer resistance protein (BCRP), multidrug 2 (MRP2), MRP4, organic transporter 3]. It therefore frequently used as probe clinical drug-drug interaction (DDI) studies to investigate inhibition. Although each these...
In the last decade, sequencing methods like Hi-C have made it clear genome is intricately folded, and that this organization contributes significantly to control of gene expression thence cell fate behavior. Single-cell DNA tracing microscopy polymer physics-based simulations folding proposed these population-scale patterns arise from motor- driven, heterogeneous movement, rather than stable 3D genomic architecture, implying motion, structure, key understanding function. However, tools...
The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices (PMDA), Food Drug Administration (FDA) have issued guidelines for conduct of drug-drug interaction studies. To examine applicability these regulatory recommendations specifically induction, a group scientists, under auspices Metabolism Leadership Group Innovation Quality (IQ) Consortium, formed Induction Working (IWG). A team 19 from 16 39 pharmaceutical companies that are members IQ Consortium two Contract Research...
Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization will help to better understand their utility predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis lines by evaluating compensatory changes mRNA expression, quantifying amounts protein liquid chromatography-tandem mass spectrometry, active...
Abstract Neuronal activity sculpts brain development by inducing the transcription of genes such as brain‐derived neurotrophic factor ( Bdnf ) that modulate function synapses. Sensory experience is transduced into changes in gene via activation calcium signaling pathways downstream both L‐type voltage‐gated channels (L‐ VGCC s) and NMDA ‐type glutamate receptors NMDAR s). These converge on regulation factors including calcium‐response (Ca RF ). Although Ca dispensable for transcriptional...