A5049161278- Cytomegalovirus and herpesvirus research
- RNA Research and Splicing
- Herpesvirus Infections and Treatments
- RNA regulation and disease
- Adenosine and Purinergic Signaling
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Synthesis and Biological Evaluation
- Receptor Mechanisms and Signaling
- Liver Disease Diagnosis and Treatment
- Viral-associated cancers and disorders
- Circular RNAs in diseases
- RNA and protein synthesis mechanisms
- Adipose Tissue and Metabolism
- Viral Infections and Immunology Research
- Brain Tumor Detection and Classification
- Cancer-related molecular mechanisms research
- Calcium signaling and nucleotide metabolism
- Synthesis and properties of polymers
- Reproductive System and Pregnancy
- Immune Cell Function and Interaction
- Synthesis and Reactions of Organic Compounds
- Reproductive Biology and Fertility
- Advanced MRI Techniques and Applications
- Diet and metabolism studies
Singapore Bioimaging Consortium
2023-2024
Agency for Science, Technology and Research
2023-2024
University of Iowa
2017-2022
University of North Carolina at Chapel Hill
2013-2017
National Institute of Diabetes and Digestive and Kidney Diseases
2013
National Institutes of Health
2013
Indiana University School of Medicine
2013
The nucleotide-sugar–activated P2Y<sub>14</sub> receptor (P2Y<sub>14</sub>-R) is highly expressed in hematopoietic cells. Although the physiologic functions of this remain undefined, it has been strongly implicated recently immune and inflammatory responses. Lack availability receptor-selective high-affinity antagonists impeded progress studies most eight nucleotide-activated P2Y receptors. A series molecules were identified by Gauthier et al. (Gauthier al., 2011) that exhibited antagonist...
Oxidative stress has pervasive effects on cells but how they respond transcriptionally upon the initial insult is incompletely understood. We developed a nuclear walk-on assay that semi-globally quantifies nascent transcripts in promoter-proximal paused RNA polymerase II (Pol II). Using this conjunction with ChIP-Seq, vitro transcription, and chromatin retention assay, we show within minute, hydrogen peroxide causes accumulation of Pol near promoters enhancers can best be explained by rapid...
ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation Zfp36l2 that results decreased expression of form which 29 N-terminal amino acid residues have deleted, ΔN-ZFP36L2, leads to fertilized eggs arrest at two-cell stage. Interestingly, homozygous ΔN-Zfp36l2 females strain release 40% fewer than WT littermates (Ramos et al., 2004), suggesting an additional defect ovulation and/or oocyte maturation....
Herpesvirus late promoters activate gene expression after viral DNA synthesis has begun. Alphaherpesviruses utilize a immediate-early protein to do this, whereas beta- and gammaherpesviruses primarily use 6-member set of late-acting transcription factors (LTF) that are drawn TATT sequence in the promoter. The betaherpesvirus, human cytomegalovirus (HCMV), produces three 2 isoforms, IE2-86, IE2-60, IE2-40, infection, but whether they is unknown. Here, we quickly degrade IE2 proteins infection...
The large genome of human cytomegalovirus (HCMV) is transcribed by RNA polymerase II (Pol II). However, it not known how closely this betaherpesvirus follows host transcriptional paradigms. We applied PRO-Seq and PRO-Cap methods to profile quantify transcription initiation productive elongation across the virus genomes in late infection. A major similarity between viral that treatment cells with P-TEFb inhibitor flavopiridol preempts virtually all elongation, which otherwise covers most HCMV...
Abstract Interactions of the RNA polymerase II (Pol II) preinitiation complex (PIC) and paused early elongation complexes with first downstream (+1) nucleosome are thought to be functionally important. However, current methods limited for investigating these relationships, both cellular chromatin human cytomegalovirus (HCMV) genome. Digestion DNA fragmentation factor (DFF) before immunoprecipitation (DFF-ChIP) precisely revealed similarities major differences in PICs driven by TBP on host...
Circular RNAs (circRNAs) are highly stable, covalently closed that regulated in a spatiotemporal manner and whose functions largely unknown. These molecules have the potential to be incorporated into engineered systems with broad technological implications. Here we describe switch for inducing back-splicing of an circRNA relies on CRISPR endoribonuclease, Csy4, as activator circularization. The endoribonuclease activity 3′ end-stabilizing properties Csy4 particularly suited this task....
How human cytomegalovirus (HCMV) infection impacts the transcription of host genome remains incompletely understood. Here, we examine global consequences primary foreskin fibroblasts (HFFs) on by RNA polymerase I, II, and III over course a lytic using PRO-Seq. The expected rapid induction innate immune response genes is observed with specific subsets exhibiting dissimilar expression kinetics. We find minimal effects Pol II initiation, but increased rates release paused into productive...
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic human and its comorbidities. The progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions refined diets is introduced to ensure reproducibility minimize species differences. LIDPAD recapitulates...
HCMV infects more than half of the world population and persists lifelong in its hosts. Although generally asymptomatic, infection can lead to life-threating disease immunosuppressed individuals.
Extended N4-(3-arylpropyl)oxy derivatives of uridine-5′-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y2/4R) or UDP (P2Y6R). The potent P2Y4R-selective N4-(3-phenylpropyl)oxy agonist was phenyl ring-substituted replaced with terminal heterocyclic naphthyl rings retention P2YR potency. This broad tolerance for steric bulk a distal region not observed...
Beta- and gammaherpesviruses late transcription factors (LTFs) target viral promoters containing a TATT sequence to drive after DNA replication has begun. Human cytomegalovirus (HCMV), betaherpesvirus, uses the UL87 LTF bind both host RNA polymerase II (Pol II), whereas UL79 been suggested productive elongation. Here we apply integrated functional genomics (dTag system, PRO-Seq, ChIP-Seq, promoter function assays) uncover contribution of diversity in sequences determining degree scope which...
4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y6R agonist for fluorescent labeling, we probed two positions (N4 and γ-phosphate cytidine derivatives) with various functional groups, including alkynes click chemistry. Functionalization extended imino substituents at the 4 position nucleobase CDP preserved generally better than γ-phosphoester formation in CTP derivatives....
ZFP36L2 (L2) destabilizes AU-rich element (ARE)-containing transcripts and has been implicated in female fertility. We have shown that only one of three putative AREs within the 3′ UTR murine luteinizing hormone receptor mRNA, ARE2197 (UAUUUAU), is capable interacting with L2. To assess whether structural elements could explain this unique binding ability, we performed whole-transcript SHAPE-MaP (selective 2′ hydroxyl acylation by primer extension-mutational profiling) full-length mLHR mRNA....
Approximately half of purified mammalian RNA polymerase II (Pol II) is associated with a tightly interacting sub-stoichiometric subunit, Gdown1. Previous studies have established that Gdown1 inhibits transcription initiation through competitive interactions general factors and blocks the Pol termination activity factor 2 (TTF2). However, biological functions remain poorly understood. Here, we utilized genetic, microscopic, multi-omics approaches to functionally characterize in three human...
Motivation: There is a lack of comprehensive understanding regarding the impact choline kinase inhibition and standard chemotherapy on preclinical GBM models. Goal(s): The primary goal this study was to elucidate treatment response mechanism in mouse model. Approach: MRS IVIM-DWI were used for monitoring metabolic microstructural changes model by single or combination therapy with inhibitor TMZ. Results: Our findings indicate that most effective regimen. This contributes better mechanisms...
Abstract Interactions of the RNA polymerase II (Pol II) preinitiation complex (PIC) and paused early elongation complexes with first downstream (+1) nucleosome are thought to be functionally important. However, current methods limited for investigating these relationships, both cellular chromatin human cytomegalovirus (HCMV) genome. Digestion DNA fragmentation factor (DFF) before immunoprecipitation (DFF-ChIP) precisely revealed similarities major differences in PICs driven by TBP on host...
ABSTRACT Adaptive T-cell immune response is essential in conferring protective immunity, a process requiring tight cellular homeostasis regulation. Pathological intrahepatic landscape has role NAFLD propagation; however, its activation remains unknown. To address this gap, we extensively characterized novel diet-induced murine model (LIDPAD) featuring key phenotypic and genetic attributes reflective of human NAFLD. Comparative transcriptomic-guided staging NASH reinforced the robustness...