Project description:The aging of pancreatic beta-cells may undermine their ability to compensate for insulin resistance, leading to the development of type 2 diabetes (T2D). Aging beta-cells acquire markers of cellular senescence and develop a senescence-associated secretory phenotype (SASP) that can lead to senescence and dysfunction of neighboring cells through paracrine actions, contributing to beta-cell failure. Herein, we defined the beta-cell SASP signature based on unbiased proteomic analysis of conditioned media of cells obtained from human senescent beta-cells. These experiments revealed that the beta-cell SASP is enriched for factors associated with inflammation, cellular stress response, and extracellular matrix remodeling across species.
Project description:TRIM28, a multi-domain protein, is crucial in the development of mouse embryos and the maintenance of embryonic stem cells (ESC) self-renewal potential. As the epigenetic factor modulating the structure of chromatin, TRIM28 regulates the expression of numerous genes and is associated with progression and poor prognosis in many types of cancer. IPSC served as a model of the cells with stem cell-like phenotype, e.g., cancer stem cells. We evaluated the role of TRIM28 in pluripotency maintenance in iPSC by silencing endogenous TRIM28 expression with siRNA (iPSC-siTRIM28). IPSC treated with siRNA with no target sequence served as a control (siCTRL) of the experiment. Cells lacking TRIM28 lose the expression of pluripotency markers, as well as the ability to self-renew, and they start to differentiate. Pathway enrichment analysis using Gene Ontology datasets showed significant upregulation of pathways related to apoptosis, differentiation, cellular response to DNA damage stimulus and cell cycle regulation in iPSC-siTRIM28, relative to reference iPSC (iPSC-WT and iPSC-siCTRL).
Project description:Hematopoietic stem cells (HSCs) primarily reside in the bone marrow, where they receive external cues from their local microenvironment. The complex milieu of biophysical cues, cellular components, and cell-secreted factors regulates the process by which HSC produce the blood and immune system. We previously showed direct co-culture of primary murine hematopoietic stem and progenitor cells with a population of marrow-derived mesenchymal stromal and progenitor cells (MSPCs) in a methacrylamide-functionalized gelatin (GelMA) hydrogel improves hematopoietic progenitor maintenance. However, the mechanism by which MSPCs influenced HSC fate decisions remained unknown. Herein, we report the use of proteomic analysis to correlate HSC phenotype to a broad candidate pool of 200 soluble factors produced by combined mesenchymal and hematopoietic progeny. Partial Least Squares Regression (PLSR), along with an iterative filter method, identified TGFβ-1, MMP-3, c-RP, and TROY as positively correlated with HSC maintenance. Experimentally, we then observe exogenous stimulation of HSC monocultures in GelMA hydrogels with these combined cytokines increases the ratio of hematopoietic progenitors to committed progeny after a 7-day culture 7.52 ± 3.65 fold compared to non-stimulated monocultures. Findings suggest a cocktail of the downselected cytokines amplify hematopoietic maintenance potential of HSCs beyond that of MSPC-secreted factors alone. This work integrates empirical and computation methods to identify cytokine combinations to improve HSC maintenance within an engineered HSC niche, suggesting a route towards identifying feeder-free culture platforms for HSC expansion.
Project description:To compare the cell signaling events between PC-3 cells and MDA-MB-468 cells, we performed a Reverse Phase of Protein Array (RPPA) profiling on 468 and PC-3 Cells that treated with DMSO, AZD5363, MS21 at 1µM for 24hr respectively.
Project description:Using high-throughput antibody microarray, through cross-sectional sample detection and verification of samples that had undergone physical changes over time, it was found that people with balanced constitution and dampness constitution in Chinese medicine showed differences in serum protein expression. The differences were expressed as the level changes of 19 proteins such as Dectin-2, Siglec-7, AIF and TACI. The research results provided the basis for the scientific expression of traditional Chinese medicine (TCM) constitution.
Project description:Innate immune PRRs sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. Here we utilize a model of inflammation resulting from accrual of self DNA (DNase II-/- Ifnar-/-) to understand the role of PRR sensing pathways in arthritis and autoantibody production. Using mice deficient in DNase II/Ifnar together with deficiency in either STING or AIM2 (TKO), we reveal central roles for the STING and AIM2 pathway in arthritis. AIM2 TKO mice show limited inflammasome activation and, like STING TKO mice, have reduced inflammation in joints. Surprisingly, autoantibody production is maintained in AIM2 and STING TKO mice, while DNase II-/- Ifnar-/- mice also deficient in Unc93b, a chaperone required for TLR7/9 endosomal localization, fail to produce autoantibodies to nucleic acids. Collectively, these data support distinct roles for cytosolic and endosomal nucleic acid sensing pathways in disease manifestations.
Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.
Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.
Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.