Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Current human pluripotent stem cells lack the transcription factor circuitry that governs the ground state of mouse embryonic stem cells (ESC). Here we report that short-term expression of two components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Inhibition of ERK and protein kinase C signalling sustains a transgene-independent rewired state. Reset cells self-renew continuously without ERK signalling, are phenotypically stable and karyotypically intact. They differentiate in vitro and form teratomas in vivo. Metabolism is reprogrammed in reset cells with activation of mitochondrial respiration as in ESC. DNA methylation is dramatically reduced and transcriptome state is globally realigned across multiple cell lines. Depletion of ground state transcription factors, TFCP2L1 or KLF4 has marginal impact on conventional human pluripotent stem cells, but collapses the reset state. These findings demonstrate feasibility of installing and propagating functional control circuitry for ground state pluripotency in human cells. DNA methylation analysis in Conventional and Reset human embryonic stem cells by whole genome bisulfite sequencing, in triplicate, using the Illumina platform
Project description:We screened the genome of OCI-Ly-7, a Diffuse Large B-cell Lymphoma cell line, for genes mediating the response to rituximab treatment. We utilized the genome-wide library GeCKO v2 (A+B) from Feng Zhang. (Addgene#1000000049)
Project description:Genome-wide CRISPR screens were performed in Huh-7 hepatoma cell line to identify genes regulating ferroptosis sensitivity. Huh-7 cells were transduced with Human GeCKO library and selected by RSL-3.
Project description:Multiomics of faecal samples collected from individuals in families with multiple cases of type 1 diabetes mellitus (T1DM) over 3 or 4 months. Metagenomic and metatranscriptomic sequencing and metaproteomics were carried out, as well as whole human genome sequencing. Phenotypic data is available.