A5012730403- Retinal Development and Disorders
- Retinal Diseases and Treatments
- HIV-related health complications and treatments
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Mitochondrial Function and Pathology
- Redox biology and oxidative stress
- COVID-19 and Mental Health
- MicroRNA in disease regulation
- Ubiquitin and proteasome pathways
- HIV/AIDS Research and Interventions
- COVID-19 Pandemic Impacts
- Retinal and Optic Conditions
- Corneal Surgery and Treatments
- Retinoids in leukemia and cellular processes
- Ocular Diseases and Behçet’s Syndrome
- Cell death mechanisms and regulation
- interferon and immune responses
- Telomeres, Telomerase, and Senescence
- Microtubule and mitosis dynamics
- Diet and metabolism studies
- Virus-based gene therapy research
- Hippo pathway signaling and YAP/TAZ
- Corneal surgery and disorders
- RNA regulation and disease
Harvard University
2013-2024
Massachusetts Eye and Ear Infirmary
2013-2024
Fudan University
2020-2023
Zhejiang Center for Disease Control and Prevention
2018-2023
Center for Disease Control
2023
University of Massachusetts Chan Medical School
2017-2022
University of Ottawa
2020
MRC Unit for Lifelong Health and Ageing
2020
University College London
2020
Taizhou People's Hospital
2019
Increased methylation of CpG islands and silencing affected target genes is frequently found in human cancer; however, vivo the question causality has only been addressed by loss-of-function studies. To directly evaluate role mechanism de novo tumor development, we overexpressed DNA methyltransferases Dnmt3a1 Dnmt3b1 Apc Min/+ mice. We that enhanced number colon tumors mice approximately twofold increased average size colonic microadenomas, whereas had no effect. The overexpression caused...
Genome-wide DNA hypomethylation and concomitant promoter-specific tumor suppressor gene hypermethylation are among the most common molecular alterations in human neoplasia. Consistent with notion that both promoter genome-wide functionally important tumorigenesis, genetic and/or pharmacologic reduction of methylation levels results suppression or promotion incidence, respectively, depending on cell type. For instance, promotes tumors rely predominantly loss heterozygosity (LOH) chromosomal...
Mitochondrial DNA (mtDNA) damage may be associated with age-related diseases, such as macular degeneration (AMD). The present study was designed to test whether the frequency of mtDNA damage, heteroplasmic mutations, and repair capacity correlate progression AMD.Macular peripheral RPE cells were isolated cultured from human donor eyes without AMD. stages AMD graded according Minnesota Grading System. Confluent primary used endogenous by quantitative PCR. Mutation detection kits detect...
Exposure to antibiotics during pregnancy can pose a systematic effect on human health. A few biomonitoring studies have demonstrated an extensive exposure of children antibiotics, but there is still lack data for pregnant women. To assess the women and potential health risk, we investigated 536 aged 16–42 years from two geographically different study sites in Eastern China 2015. We measured 21 five categories (seven fluoroquinolones, three phenicols, four tetracyclines, macrolides,...
Purpose.: Micro(mi)RNAs negatively regulate a wide variety of genes through degradation or posttranslational inhibition their target genes. The purpose this study was to investigate the role miR-23a in modulating RPE cell survival and gene expression response oxidative damage. Methods.: level measured macular retinal pigment epithelial (RPE) cells donor eyes with aged-related degeneration (AMD) age-matched normal by using qRT-PCR. Cultured human ARPE-19 were transfected mimic inhibitor. Cell...
The attachment of kinetochores to spindle microtubules (MTs) is essential for maintaining constant ploidy in eukaryotic cells. Here, biochemical and imaging data presented demonstrating that the budding yeast CLIP-170 orthologue Bik1is a component kinetochore-MT binding interface. Strikingly, Bik1 not required viability haploid cells, but becomes polyploids. ploidy-specific requirement BIK1 enabled us characterize without eliminating nonhomologous genes, providing new approach circumventing...
Aberrant gene silencing accompanied by DNA methylation is associated with neoplastic progression in many tumors that also show global loss of methylation. Using conditional inactivation de novo methyltransferase Dnmt3b Apc(Min/+) mice, we demonstrate the has no impact on microadenoma formation, which considered earliest stage intestinal tumor formation. Nevertheless, observed a significant decrease formation macroscopic colonic adenomas. Interestingly, large adenomas showed regions...
Photoreceptor cell death is the definitive cause of vision loss in retinal detachment (RD). Mammalian STE20-like kinase (MST) a master regulator both and proliferation critical factor development tumorigenesis. However, to date role MST neurodegeneration has not been fully explored. Utilizing MST1−/− MST2−/− mice we identified MST2, but MST1, as photoreceptor mouse model RD. demonstrated significantly decreased outer nuclear layer (ONL) thinning after Additionally, caspase-3 activation was...
Purpose: TUNEL assay is widely used to evaluate cell death. Quantification of TUNEL-positive (TUNEL+) cells in tissue sections usually performed manually, ideally by two masked observers. This process time consuming, prone measurement errors, and not entirely reproducible. In this paper, we describe an automated quantification approach address these difficulties. Methods: We developed ImageJ macro quantitate death retinal cross-section images. The script was coded using IJ1 programming...
Gut microbiota is closely related to age. Studies from Europe and the U.S. identified featured in different age groups for elderly. Asian studies mainly focused on people living longevity areas. Featured elderly of groups, especially centenarian general population, has not been well investigated China.We conducted a comparative study by including 198 subjects three (65-70, 90-99, 100+ years) East China. Information regarding age, sex, height, weight, waist circumference, hip food preference,...
AbstractUbiquitin-specific processing proteases (UBPs) presently form the largest enzyme family in ubiquitin system, characterized by a core region containing conserved motifs surrounded divergent sequences, most commonly at N-terminal end. The functions of these sequences remain unclear. We identified two isoforms novel testis-specific UBP, UBP-t1 and UBP-t2, which contain identical regions but distinct N termini, thereby permitting dissection regions. Both were germ cell specific...
The protease HTRA-1 is closely associated with rheumatoid arthritis (RA). molecular mechanisms that control expression are currently unknown. This study was undertaken to determine the regulatory role of Toll-like receptors (TLRs) on in mice collagen-induced (CIA) and synovial cells from RA patients.HTRA-1 messenger RNA protein production mouse fibroblasts, macrophages, freshly isolated patient treated TLR ligands were detected by real-time polymerase chain reaction enzyme-linked...
The high temperature requirement A1 (HTRA1) is a potent protease involved in many diseases, including rheumatoid arthritis (RA). However, the regulatory mechanisms that control HTRA1 expression need to be determined. In this study, we demonstrated IFN-γ significantly inhibited basal and LPS-induced fibroblasts macrophages, which are two major cells for production RA. Importantly, inhibitory effect of on was evidenced collagen-induced (CIA) mouse models human RA synovial cells. parallel with...
Oxidative stress has been shown to contribute the development of age-related macular degeneration (AMD). MicroRNAs (miRNA) are small non-coding RNA molecules that function in silencing and post-transcriptional regulation gene expression. We showed miR-17-3p be elevated RPE cells from AMD patients ARPE-19 under oxidative stress. Transfection mimic induced cell death exacerbated lethality was alleviated by inhibitor. The expression antioxidant enzymes manganese superoxide dismutase (MnSOD)...
HIV infection and normal aging share immune inflammatory changes that result in premature non-communicable diseases (NCDs), but the exact pathophysiology is not yet uncovered. We identified common metabolic pathways underlying various NCDs treated infection.We performed untargeted metabolomics including 87 HIV-negative (-) controls (NCs), HIV-positive (+) NCs, 148 HIV+ subjects with only one type of NCDs, namely, subclinical carotid atherosclerosis, neurocognitive impairment (NCI), liver...
Ubiquitin-specific processing proteases (UBPs) are characterized by a conserved core domain with surrounding divergent sequences, particularly at the N-terminal end. We previously cloned two isoforms of testis UBP, UBP-t1 and UBP-t2, which contain identical regions but distinct N termini that target to different subcellular locations (Lin, H., Keriel, A., Morales, C. R., Bedard, N., Zhao, Q., Hingamp, P., Lefrancois, S., Combaret, L., Wing, S. (2000) Mol. Cell. Biol. 20, 6568–6578). To...
Coke oven workers (COWs) are exposed to high level of genotoxic chemicals that induce oxidative stress and genetic damage. The dietary intake certain types foods may reverse these effects.We conducted a cross-sectional study with 51 topside COWs, 79 other 67 controls, assess the effects patterns on damage.Compared both COWs had significantly higher urinary 1-hydroxypyrene levels, serum oxidant levels [malondialdehyde, (MDA)], damage [micronucleus (MN) frequency & 8-oxo-2'-deoxyguanosine...
The PML-RARα oncogene is the central effector of acute promyelocytic leukemia (APL). physically interacts with epigenetic-modifying enzymes including DNA methyltransferases (Dnmt) to suppress critical downstream targets. Here, we show that increased expression Dnmt3a1 cooperates in vivo promote early lethality secondary myeloid expansion and dysfunction primary mice. Bone marrow cells from these mice cause leukemogenesis a shortened latency higher penetrance on transplantation into...
Phagocytosis of daily shed photoreceptor outer segments is an important function the retinal pigment epithelium (RPE) and it essential for homeostasis. RPE dysfunction, especially impairment its phagocytic ability, plays role in pathogenesis age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on cells has not...