Project description:Nucleotide-binding oligomerization domain 2 (Nod2) signaling is critical for human health.To figure out the clinical relevance of NOD2 ligands, the investigators plan to evaluate the change of NOD2 ligands in inflammatory bowel diseases (IBD), CRC, atherosclerotic cardiovascular disease (ACVD), and type 2 diabetes mellitus (DM2 ).
Project description:We undertook a unbiased genome-wide haploid genetic screen to identify new components in interferon lambda signaling. In addition, we performed a genome-wide screen to identify genes that repress spontaneous activation of interferon stimulated genes in the absence of interferon. Both of these screens were performed using a HAP1 cell line containing GFP reporter under the transcriptional regulation of the Interferon-Stimulated Response Element from IFIT2. We also overexpressed IL28RA (IFNLR1) in this cell line, in order to sensitize the cells to type III interferon
Project description:To search for factors regulating neuronal differentiation, we performed a genome-wide loss-of-function CRISPR/Cas9 screen in haploid human ESCs. The regulators were identified by the quantification of depletion of their mutant clones within a pooled loss-of-function library upon neuronal differentiation.
Project description:To search for factors regulating paternally imprinted genes (PEGs), we performed a genome-wide loss-of-function CRISPR/Cas9 screen in haploid parthenogenetic ESCs. This by staining a pooled CRISPR library with a PEG10 antibody and next FACS-sorted for cells that presented de-novo PEG10 expression.
Project description:RIPK2 mediates inflammatory signaling by the bacteria-sensing receptors NOD1 and NOD2, and inhibition of RIPK2 by kinase inhibitors is an emerging strategy to ameliorate NOD-mediated pathologies. However, the role for RIPK2’s kinase activity remains unclear. Here, we reveal that RIPK2 kinase activity is dispensable for NOD2 inflammatory signaling and show that RIPK2 inhibitors function instead by antagonizing XIAP-binding and XIAP-mediated ubiquitination of RIPK2. We map the XIAP binding site on RIPK2 to the loop between 2 and 3 of the N-lobe of the kinase, which is in close proximity to the ATP-binding pocket. Through characterization of a new series of ATP-competitive RIPK2 inhibitors, we identify the molecular features that determine their inhibition of both the RIPK2-XIAP interaction, and of cellular and in vivo NOD2 signaling. Our study exemplifies how targeting of the ATP-binding pocket in RIPK2 can be exploited to interfere with the RIPK2-XIAP interaction for modulation of NOD signaling.
Project description:To search for host factors regulating Zika virus infection, we performed a genome-wide loss-of-function CRISPR/Cas9 screen in haploid human ESCs. The regulators were identified by the quantification of enrichment of their mutant clones within a pooled loss-of-function library upon Zika virus infection.
Project description:To search for host factors regulating SARS-COV-2 infection, we performed a genome-wide loss-of-function CRISPR/Cas9 screen in haploid human ESCs. The regulators were identified by the quantification of enrichment of their mutant clones within a pooled loss-of-function library upon SARS-COV-2 infection.
