Project description:The DNA exonuclease TREX1 degrades endogenous cytosolic DNA. Cytosolic DNA triggers the cGAS/STING pathway which increases type I interferon. To investigate the physiological significance of TREX1 loss on in vivo tumor growth, we implanted control and TREX1-deficient CT26 tumor cells into immunocompetent BALB/c hosts.Tumor cells were collected 7 days after tumors reached around 200mm3.
Project description:To better understand the mechanism underlying the invasion and migration phenotype instigated by EFEMP1 EVs (extracellular vesicles), we performed RNA sequencing analysis on BT549 cells treated with control and EFEMP1KD EVs.
Project description:To better understand the mechanisms downstream of IL-27 signaling, we performed RNA sequencing on repetitively stimulated OT-I T cells treated with IL-27.
Project description:To understand the role of IL-27 receptor agonism in tumor regression in mice, we examined Cd4 T conventional T cells and Tregs from tumor and lymph node.
Project description:Double-stranded RNA (dsRNA) is an established trigger of innate immunity, activating intrinsic and extrinsic cellular response mechanisms. While this response is typically associated with viral infection, it has also been shown that accumulation of self-derived dsRNAs known as endoge-nous dsRNA, also have the capacity to activate similar innate pathways. However, the extent to which endogenous dsRNA is dynamically regulated during normal cellular non-immune homeo-stasis, as opposed to pathological states, remains poorly understood. This raises important ques-tions about the physiological roles of dsRNA and the mechanisms that restrain its immunostimu-latory potential. Here, we aim to characterize the presence of endogenous dsRNA within the skin at steady state and understand its accumulation during differentiation, wound healing and within hair follicle stem cell niches. We find that dsRNA is predominantly localized to basal progenitor epidermal keratinocytes under homeostatic conditions and is upregulated in wound healing areas that later harbor neogenic hair follicle morphogenesis. Notably, we also observed upregulation of dsRNA during a transient state of hair follicle stem cell activation, suggesting a role in maintain-ing progenitor multipotency and directing early differentiation. Given the essential role of dsRNA and its capacity to induce regeneration, uncovering the mechanisms that govern its accumulation will reveal the regulatory machinery that influences cell fate and holds therapeutic potential.
Project description:The ATP binding cassette (ABC) transporter family is widely distributed in vertebrates and is essential for drug resistance, cell signaling and energy homeostasis. There is growing evidence that various ABC transporters contribute to the growth and development of tumors but relatively little is known about how the ABC transporter family behaves in hepatocellular carcinoma (HCC). ABCC6 transporter was downregulated in HCC tissues and that it was associated with successful treatment for HCC patients. Cellular model studies have shown that ABCC6 plays a role in the migration and cytoskeleton rearrangement of HepG2 hepatocarcinoma cells, highlighting its role in cancer biology. Abcc6-silenced HepG2 cells are used as cell model to obtain more deep information about the molecular mechanisms underlying the observed results. MTT and colony formation assays, showed the effects of Abcc6 on HepG2 cell proliferation. Western blotting analysis, real-time PCR, and immunofluorescence were used to find the E-cadherin, Vimentin, and N-cadherin markers associated with the epithelial-to-mesenchymal transition (EMT). Colony formation experiments in the current study showed that Abcc6 decreased HepG2 cell viability. The migratory and invasion activities were dramatically slowed down by Abcc6 silencing, according to the Transwell and wound-healing assays. In tumor cells, EMT has been shown to be crucial for enhancing migration and invasion and is frequently characterized by a loss of epithelial markers (E-cadherin) and an increase in mesenchymal markers (Vimentin and N-cadherin). In the western blotting examination, E-cadherin expression was considerably elevated compared to the control group, while N-cadherin and Vimentin expression were downregulated. This led to the hypothesis that the underlying mechanism of Abcc6 knockdown prevents migration and invasion in HepG2 cells and is linked to the suppression of EMT. In conclusion all evidence suggested that ABC transporters play a more active role in cancer biology.
Project description:Two medulloblastoma cell lines (ONS-76 and HDMB-03) were grown in 3D hyaluronan hydrogels for three weeks. We observed nodules forming showing different behavior and wanted to evaluate if these different nodules (slow vs fast vs non-growing, migrating and invading cells) are also characterised by different gene expression patterns. We performed this experiment on a SHH (ONS-76) and on a group 3 MB (HDMB-03) cell line to compare if certain subpopulations would be unique for the subgroups.