Project description:The TeloVac study indicated that GV1001 did not to improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC) patients. However, the cytokine examinations of the study suggested that high serum eotaxin levels may predict responses to GV1001. This phase III trial aimed to assess the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated locally advanced and metastatic PDAC. In addition, we proposed potential blood markers to predict response to GV1001 treatment based on correlative studies.
Project description:Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, we interrogated serum from subjects who received 2 doses of inactivated monovalent influenza A/Indonesia/05/2005 vaccine with or without AS03 or MF59 using hemagglutinin (HA) microarrays (NCT01317758 and NCT01317745). The arrays were designed to reflect both full length and globular head HA derived from 17 influenza A subtypes (H1 to H16 and H18) and influenza B strains. We observed significantly increased strain-specific and broad homo- and hetero-subtypic antibody responses with both AS03 and MF59 adjuvanted vaccination with AS03 achieving a higher titer and breadth of IgG responses relative to MF59. Adjuvanted vaccine was also associated with the elicitation of stalk directed antibody. We established good correlation of the array antibody responses to H5 antigens with standard HA inhibition and microneutralization titers.
Project description:Estrogen insensitivity syndrome (EIS) arises from rare mutations in ERα resulting in the inability of estrogen to exert its biological effects. Due to the rarity, mutations in ESR1 gene and the underlying molecular mechanisms of EIS have not been thoroughly studied. We used PamChip array with 154 coregulator motifs (PamGene #88101) array to compare the peptide profiles between the WT and 5 of Q375 mutants in HEK293 cells after transferred with ER alpha or Q375 mutatnts. 93 ligand-modulated peptides were reported here.
Project description:Two glioblastoma cell lines (LN18 and HS863) were stable transfected with control empty vector (EV) or RNF123-vector (KPC1). The objective of this experiment was to determine NFKB1-targets regulated by RNF123 overexpression in glioblastoma cell lines. To do that LN18 and HS863 cell lines with RNF123 overexpression were compared to control empty vector. In the present study, we utilized the combination of RPPA and RNA-Sequencing. By comparing both datasets, we identified commonly proteins and genes differentially expressed in control versus RNF123-overexpressing cells.
Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults.
Project description:Kidney fibrosis represents an urgent unmet clinical need due to the lack of effective therapies and inadequate understanding of the molecular pathogenesis. We have generated a comprehensive and integrated multi-omics data set (proteomics, mRNA and small RNA transcriptomics) of fibrotic kidneys that is searchable through a user-friendly web application. Two commonly used mouse models were utilized: a reversible chemical-induced injury model (folic acid (FA) induced nephropathy) and an irreversible surgically-induced fibrosis model (unilateral ureteral obstruction (UUO)). mRNA and small RNA sequencing as well as 10-plex tandem mass tag (TMT) proteomics were performed with kidney samples from different time points over the course of fibrosis development. The bioinformatics workflow used to process, technically validate, and integrate the single data sets will be described. In summary, we present temporal and integrated multi-omics data from fibrotic mouse kidneys that are accessible through an interrogation tool to provide a searchable transcriptome and proteome for kidney fibrosis researchers.
Project description:This study employed the NanoString nCounter platform to perform targeted, quantitative molecular profiling of longitudinally collected FFPE tumor samples to elucidate molecular mechanisms underlying resistance to anti–PD-1 therapy. nCounter® Vantage 3D™ Single Nucleotide Variant assay was integrated using a solid tumor panel to screen 104 driver variants across 25 genes frequently mutated in solid tumors. We quantified the expression of 770 cancer-related mRNA transcripts to identify persistently activated oncogenic pathway signatures in non-responders, which were further complemented by quantitative profiling of 27 total and phosphoproteins using antibody–oligonucleotide conjugates for functional validation of pathway activity. To characterize the tumor microenvironment spatially, GeoMx Digital Spatial Profiler analysis was utilized to assess the distribution of 38 proteins across distinct histological regions, revealing an immunosuppressive spatial architecture associated with treatment resistance.
Project description:Protein and phosphorylation (Phospho Explorer Antibody Array, FullMoonBioscience, #PEX100) profiling of peritoneal monocytes (pooled lavages from 3-4 mice / condition) was carried out according to the manufacturer’s instructions.
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.