Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Nipah virus (NiV) is an emerging paramyxovirus which causes severe respiratory illness and deathly encephalitis in humans.Improving the ability of vaccines to induce strong, cellular, and humoral immune responses, remains the challenge to respond to Nipah and future Henipavirus infections rapidly and efficiently. A CD40.NiV vaccine has been engineered by fusing to the anti-CD40 monoclonal Ab the ectodomain of the Nipah G protein (Bangladesh strain) and immunogenic and conserved NiV F and N peptides. In mice, CD40.NiV promotes poly-antigenic T cell responses and significantly improves anti-NiV G IgG responses compared to the non-targeted NiV G immunogenic protein, in terms of avidity and neutralization potency. Immunogenicity was confirmed in the AGM (African Green Monkey) model, with induction of cross-neutralizing sera against circulating NiV strains and Hendra virus (HeV). Challenge experiment using NiV-B strain demonstrated the high protective efficacy of the vaccine with 100% survival in vaccinated group as compared to 100% lethality in controls. Surviving animals did not exhibit NiV viral replication in the blood, organs and swabs suggesting a sterilizing immunity conferred by the CD40.NiV vaccine. Taken together, results obtained with CD40.NiV vaccine are highly promising in terms of breadth and viral efficacy against NiV.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes