A5056847430- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- Hemoglobinopathies and Related Disorders
- Genomics, phytochemicals, and oxidative stress
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Iron Metabolism and Disorders
- Liver Disease Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Folate and B Vitamins Research
- Cancer-related gene regulation
- Chromosomal and Genetic Variations
- Prenatal Screening and Diagnostics
- Cholesterol and Lipid Metabolism
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Kruppel-like factors research
- RNA regulation and disease
- Systemic Lupus Erythematosus Research
- Virus-based gene therapy research
- RNA Research and Splicing
- Immune Cell Function and Interaction
- MicroRNA in disease regulation
Augusta University
2012-2025
Augusta University Health
2018-2025
Shanghai University
2022-2024
Affiliated Hospital of Nantong University
2022-2023
Nantong University
2022-2023
Zhongda Hospital Southeast University
2022
Nanjing Sport Institute
2022
Wake Forest University
2006
Institute of Microbiology
2004
Chinese Academy of Sciences
2004
The triggering receptor expressed on myeloid cell 1 (TREM1) plays a critical role in development of chronic inflammatory disorders and the inflamed tumor microenvironment (TME) associated with most solid tumors. We examined whether loss TREM1 signaling can abrogate immunosuppressive TME enhance cancer immunity. To investigate therapeutic potential cancer, we used mice deficient Trem1 developed novel small molecule inhibitor, VJDT. demonstrated that genetic or pharmacological silencing...
In the human ε−globin gene locus, HS2 enhancer in Locus Control Region regulates transcription of embryonic ε-globin located over 10 kb away. The mechanism long-range function was not fully established. Here we show that complex containing DNA together with RNA polymerase II (pol II) and TBP tracks along intervening DNA, synthesizing short, polyadenylated, intergenic RNAs to ultimately loop promoter. Guided by this facilitated tracking mechanism, delivers pol cis-linked globin promoter...
Retrotransposons including endogenous retroviruses and their solitary long terminal repeats (LTRs) compose >40% of the human genome. Many them are located in intergenic regions far from genes. Whether these retrotransposons serve beneficial host functions is not known. Here we show that an LTR retrotransposon ERV-9 retrovirus 40-70 kb upstream fetal gamma- adult beta-globin genes serves a long-range, function. The contains multiple CCAAT GATA motifs competitively recruits high concentration...
The transsulfuration (TSS) pathway is an alternative source of cysteine for glutathione synthesis. Little the TSS in antioxidant capacity sickle cell disease (SCD) known. Here, we evaluate effects activation through cystathionine beta-synthase (CBS) to attenuate reactive oxygen species (ROS) and ferroptosis stresses SCD. A vital contribution sustaining levels detected only under hemin exposure or physiological but not supraphysiological cystine supplement. Mechanistic studies show that...
Hepatocellular carcinoma (HCC) is one of the most common digestive system cancers (DSCs) with a poor prognosis. Zinc-regulated transporter (ZRT)/iron-regulated (IRT) like protein transporters (ZIPs) encode membrane transport proteins, which are responsible for absorption zinc and play important roles in pathogenesis various human cancers. Tumor-associated macrophages (TAMs) participants regulation tumor microenvironment development HCC. Individual role each ZIP involved hepatocarcinogenesis...
Upon recognizing danger signals produced by virally infected neurons, macrophages in the central nervous system (CNS) secrete multiple inflammatory cytokines to accelerate neuron apoptosis. The understanding is limited about which key effectors regulate macrophage-neuron crosstalk upon infection. We have used neurotropic-virus-infected murine models identify that vascular endothelial growth factor receptor 3 (VEGFR-3) upregulated CNS and neurons ligand VEGF-C. When cultured with...
The human embryonic, fetal and adult β-like globin genes provide a paradigm for tissue- developmental stage-specific gene regulation. γ-globin is expressed in erythroid cells but repressed cells. molecular mechanism underlying this transcriptional switch during development not completely understood. Here, we used combination of vitro vivo assays to dissect the assemblies active proximal promoter complexes K562 erythroleukemia cell line primary We found that complex assembled by...
LTR retrotransposons are repetitive DNA elements comprising ∼10% of the human genome. However, sequences disproportionately present in long, non-coding RNAs (lncRNAs). Whether and how lncRNAs serve biological functions largely unknown. Here we show that primary erythroblasts, transcribed from ERV-9 endogenous retrovirus activated transcription key erythroid genes modulated ex vivo erythropoiesis. To dissect functional mechanism lncRNAs, performed genome-wide RNA ChIRP analyses before after...
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention increasing about how aberrant lipid and cholesterol metabolism linked together type I interferon (IFN-I) signaling in regulation pathogenesis SLE. Here, metabonomic analysis performed increased plasma concentrations oxysterols, especially 7α, 25-dihydroxycholesterol (7α, 25-OHC), are identified SLE patients. The authors find that 25-OHC binding to its receptor...
The solitary ERV-9 long terminal repeat (LTR) located upstream of the HS5 site in human beta-globin locus control region exhibits prominent enhancer activity embryonic and erythroid cells. LTR contains 14 tandemly repeated subunits with recurrent CCAAT, GTGGGGA, GATA motifs. Here we showed that K562 cells these DNA motifs bound following three transcription factors: ubiquitous NF-Y hematopoietic MZF1 GATA-2. These factors their target exhibited a hierarchy DNA/protein protein/protein binding...
Sickle cell disease (SCD) is a pathophysiological condition of chronic hemolysis, oxidative stress, and elevated inflammation. The transcription factor Nrf2 master regulator stress. Here we reported that the FDA-approved, oral agent simvastatin, an inhibitor hydroxymethyl-glutaryl coenzyme A reductase, significantly activates expression antioxidant enzymes. Simvastatin also induces fetal hemoglobin in SCD patient erythroid progenitors transgenic mouse model. alleviates symptoms by decreasing...
LTR retrotransposons are repetitive DNA elements comprising ∼10% of the human genome. They silenced by hypermethylation cytosines in CpG dinucleotides and considered parasitic serving no useful function for host However, hypermethylated LTRs contain enhancer promoter sequences can promote tissue-specific transcription cis-linked genes. To resolve apparent paradox possessing transcriptional activities, we studied ERV-9 retrotransposon located at 5' border transcriptionally active β-globin...
Sickle cell disease (SCD) is a pathophysiological condition of chronic hemolysis, oxidative stress, and elevated inflammation. The transcription factor Nrf2 master regulator stress. Here, we report that the FDA-approved oral agent simvastatin, an inhibitor hydroxymethyl-glutaryl coenzyme A reductase, significantly activates expression antioxidant enzymes. Simvastatin also induces fetal hemoglobin in SCD patient primary erythroid progenitors transgenic mouse model. alleviates symptoms by...
Hydroxyurea (HU), the first of two drugs approved by US Food and Drug Administration for treating patients with sickle cell disease (SCD), produces anti-sickling effect re-activating fetal γ-globin gene to enhance production hemoglobin. However, approximately 30% do not respond HU therapy. The molecular basis non-responsiveness is clearly understood. To address this question, we examined HU-induced changes in RNA protein levels transcription factors NF-Y, GATA-1, -2, BCL11A, TR4, MYB NF-E4...
Abstract Correlations between the oxidative stress response and metabolic reprogramming have been observed during malignant tumor formation; however, detailed mechanism remains elusive. The transcription factor Nrf2, a master regulator of response, mediates in multiple cancers. In mouse model hepatocellular carcinoma (HCC), through profiling, genome-wide gene expression, chromatin structure analyses, we present new evidence showing that addition to altering antioxidative signaling, Nrf2...