A5025098084- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Circular RNAs in diseases
- Pharmacological Receptor Mechanisms and Effects
- Chemical Synthesis and Analysis
- Genetics and Neurodevelopmental Disorders
- Computational Drug Discovery Methods
- Folate and B Vitamins Research
- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Circadian rhythm and melatonin
- Virus-based gene therapy research
- RNA Research and Splicing
- Estrogen and related hormone effects
- Iron Metabolism and Disorders
- Cancer-related molecular mechanisms research
- Calcium signaling and nucleotide metabolism
- Genomics and Rare Diseases
- Liver physiology and pathology
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Genetic Associations and Epidemiology
- BRCA gene mutations in cancer
- Cancer Treatment and Pharmacology
- Dietary Effects on Health
University of North Carolina at Chapel Hill
2014-2024
National Institute of Mental Health
2023-2024
Toho University Omori Medical Center
2024
Toho University
2024
Karolinska Institutet
2018
The Ohio State University
2010-2016
Pediatrics and Genetics
2016
North Carolina State University
2006-2013
Kyushu University
2006-2009
AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 of the σ
Inducible gene expression plays a central role in neuronal plasticity, learning, and memory, dysfunction of the underlying molecular events can lead to severe disorders. In addition coding transcripts (mRNAs), non-coding microRNAs (miRNAs) appear play these processes. For instance, CREB-regulated miRNA miR132 has been shown affect structure an activity-dependent manner, yet details its physiological effects behavioral consequences vivo remain unclear. To examine questions, we employed...
miR-132 and miR-212 are structurally related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these tandomly processed from same noncoding transcript, share a common seed sequence: thus it has difficult assess distinct contribution of each microRNA gene expression CNS. Here, we employed combination conditional knockout transgenic mouse models examine miR-132/-212 locus learning memory, then on hippocampal expression. Using...
Status epilepticus (SE) is a life-threatening condition that can give rise to number of neurological disorders, including learning deficits, depression and epilepsy. Many the effects SE appear be mediated by alterations in gene expression. To gain deeper insight into how affects transcriptome, we employed pilocarpine model mice Illumina-based high-throughput sequencing characterize expression from induction SE, development spontaneous seizure activity. While some genes were upregulated over...
An effective utilization of intracellular iron is a prerequisite for erythroid differentiation and hemoglobinization. Ferritin, consisting 24 subunits H L, plays crucial role in homeostasis. Here, we have found that the subunit ferritin gene activated at transcriptional level during hemin-induced K562 human erythroleukemic cells. Transfection various 5' regions fused to luciferase reporter into cells demonstrated hemin activates transcription through an antioxidant-responsive element (ARE)...
The MIR137 locus is a replicated genetic risk factor for schizophrenia. risk-associated allele reported to increase miR-137 expression and overexpression alters synaptic transmission in mouse hippocampus. We investigated the cellular mechanisms underlying these observed effects hippocampal neurons culture. First, we correlated of genes human postmortem brain. Some evidence increased MIR137HG was observed, especially hippocampus disease-associated genotype. Second, neurons, confirmed...
Gene therapy using recombinant adeno-associated viral (AAV) vectors is emerging as a promising approach to treat central nervous system disorders such Spinal muscular atrophy, Batten, Parkinson and Alzheimer disease amongst others. A critical remaining challenge for system-targeted gene therapy, silencing or editing limit potential vector dose-related toxicity in off-target cells organs. Here, we characterize lab-derived AAV chimeric (AAV2g9), which displays favorable attributes derived from...
Coordinated regulation of PI3-kinase (PI3K) and the tumor suppressor phosphatase tensin homologue deleted on chromosome 10 (PTEN) plays a pivotal role in various cell functions. PTEN is deficient many cancer cells, including Jurkat human leukemia. Here, we demonstrate that status determines cellular susceptibility to oxidative stress through antioxidant-responsive element (ARE)-mediated transcription detoxification genes. We found ferritin H was robustly induced tert-butylhydroquinone...
Abstract AlphaFold2 (AF2) and RosettaFold have greatly expanded the number of structures available for structure-based ligand discovery, even though retrospective studies cast doubt on their direct usefulness that goal. Here, we tested unrefined AF2 models prospectively , comparing experimental hit-rates affinities from large library docking against vs same screens targeting receptors. In σ 2 5-HT2A receptors, struggled to recapitulate ligands had previously found receptors’ structures,...
The biochemical activity of a stunning diversity cell types and organ systems is shaped by 24-hour (circadian) clock. This rhythmic drive to good deal the transcriptome (up 15% all coding genes) imparts circadian modulation over wide range physiological behavioral processes (from division cognition). Further, dysregulation clock has been implicated in pathogenesis large diverse array disorders, such as hypertension, cancer depression. Indeed, possibility utilizing therapeutic approaches that...
The CREB/CRE transcriptional pathway has been implicated in circadian clock timing and light-evoked resetting. To date, much of the work on CREB physiology focused how changes phosphorylation state regulate processes. However, beyond phosphorylation, CREB-dependent transcription can also be regulated by coactivator CRTC (CREB-regulated coactivator), known as TORC (transducer CREB). Here we profiled both rhythmic regulation CRTC1 CRTC2 murine suprachiasmatic nucleus (SCN), locus master...
ATF1 (activating transcription factor 1), a stimulus-induced CREB family factor, plays important roles in cell survival and proliferation. Phosphorylation of at Ser63 by PKA (cAMP-dependent protein kinase) related kinases was the only known post-translational regulatory mechanism ATF1. Here, we found that HIPK2 (homeodomain-interacting kinase 2), DNA-damage-responsive nuclear kinase, is new phosphorylates Ser198 but not Ser63. phosphorylation activated function GAL4-reporter system....
Resveratrol, a natural polyphenol, increases cellular antioxidant capacity by inducing the expression of battery cytoprotective genes through an responsive element (ARE). However, upstream signaling events initiated resveratrol leading to activation ARE enhancer, particularly in immune cells, have not been fully elucidated. In this study, ARE-dependent transcriptional ferritin heavy chain (ferritin H) gene was further investigated Jurkat T cells and human peripheral blood mononuclear cells....
CREB (cyclic AMP response element-binding protein) is a stimulus-induced transcription factor that plays pivotal roles in cell survival and proliferation. The transactivation function of primarily regulated through Ser-133 phosphorylation by cAMP-dependent protein kinase A (PKA) related kinases. Here we found homeodomain-interacting 2 (HIPK2), DNA-damage responsive nuclear kinase, new for at Ser-271 but not Ser-133, activates including brain-derived neurotrophic (BDNF) mRNA expression. to...
To detect estrus for reproductive management, and to determine the relationship between urinary estrogen estrous behavior, in a female giant panda, we developed evaluated rapid enzyme immunoassay (EIA) system Estrone-3-glucuronide (E1G) using commercial reagents. The EIA took only around 3 hours, including all procedures obtain result. It indicated good reproducibility (intra-assay CV of 5.16%, interassay 15.4%) sensitivity (lowest standard concentration was 0.0156 ng/ml) measurement...
In order to enable monitoring of the reproductive status female giant panda after observation estrus behavior, we developed an enzyme immunoassay (EIA) system for urinary pregnanediol-3-glucuronide (PdG), a progesterone metabolite, using commercial reagents and examined changes in concentration PdG that showed pseudopregnancy suspicious 6 consecutive years. The EIA had good reproducibility (intra- interassay CVs 6.1% 16.3%, respectively), parallelism between standard curve dose response...