Project description:Experimental V4020 is derived from VEEV TC-83, a vaccine with a long track record of use in lab and military personnel at risk. V4020 was generated from an infectious DNA clone, secured genetic stability by employing stabilizing mutation at position 120 in the E2 protein, and by rearrangement of structural genes. In this study, serial passages in brain tissues of mice were performed to compare safety and genetic stability of V4020 and TC-83 experimental vaccines. During five serial passages in brain, less severe clinical manifestations and lower viral load were observed in V4020 mice and all animals survived. In contrast, 13.3% of mice met euthanasia criteria during the passages in TC-83 group. At 2 DPI, RNA-Seq analysis of brain tissues revealed that V4020 mice had lower rates of mutations throughout five passages. Higher synonymous mutation ratio was observed in the nsP4 (RdRP) gene of TC-83 compared to V4020 mice. At 2 DPI, both viruses induced different expression profiles of host genes involved into neuro-regeneration. Taken together, these results provide evidence for the improved safety and genetic stability of the experimental V4020 VEEV vaccine in a murine model. While no single nucleotide polymorphisms that have been previously linked to virulence were identified, more neuro-virulence markers were observed in serial passaged TC-83 compared to V4020. This study suggests a complex polygenic basis for neuro-virulent reversion in VEEV live attenuated vaccines and provides evidence for the advanced safety and genetic stability of V4020.
Project description:We performed ribosome profiling (Ribo-seq) on acute myeloid leukemia patient-derived xenograft models across serial transplantation passages to characterize translational remodeling associated with leukemia propagation.
Project description:We performed Illumina Infinium MethylationEPIC array profiling of acute myeloid leukemia patient-derived xenograft models across serial transplantation passages P0, P1, and P2 to characterize DNA methylation changes associated with leukemia propagation.
Project description:We performed bulk RNA-seq profiling of acute myeloid leukemia (AML) patient-derived xenograft models across serial transplantation passages (P0, P1, P2) to characterize transcriptional changes associated with leukemia propagation and stem cell activity.
Project description:Recent clinical trials revealed that prior use of Cetuximab may interfere with ICB efficacy. In this study, STAT1 protein levels changed after continued Cetuximab treatment (500 ug/ml). We collected serial passages of cetuximab resistance HNSCC cell lines to perform LC-MS/MS. We identified the IFN pathway as the key target to cause this effect.
Project description:We carried out the analysis using human skin fibrobllast HCA2 (MJ90) cells. Cells were indcued to be senescent cells by treatment with doxorubicin for 24 hrs, tert-butyl-hydroperoxide for 24 hrs, or serial passages as well as nultin3a + RO3306. As a result, we found simailar transcriptome signatures among senescent cells induced by various stimuli
