Upcoming Events & Webinars
Join our events and webinars to meet experts, build collaborations and be the first to see new product releases.
Upcoming Webinars
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2024-10-31T08:00:00Z
Time is precious, and so are your samples. Automating the nucleic acid isolations in your human microbiome research can minimize bias while freeing up your lab group's hands (and brains) for more important work. From versatile robots to high throughput machines to affordable instruments, automation is suited for every type of lab. Join our speakers as they explore the different instruments available to automate nucleic acid isolations for human microbiome research. See how these instruments can help reduce bias, increasing the consistency and reliability of your isolations. Our speakers will also review automation best practices and explain which instruments are the most suited for your laboratory and work style.
Jan-Niklas Schulz, Director Global Product Management, Automated Solutions and 1 more -
2024-10-31T16:00:00Z
Time is precious, and so are your samples. Automating the nucleic acid isolations in your human microbiome research can minimize bias while freeing up your lab group's hands (and brains) for more important work. From versatile robots to high throughput machines to affordable instruments, automation is suited for every type of lab. Join our speakers as they explore the different instruments available to automate nucleic acid isolations for human microbiome research. See how these instruments can help reduce bias, increasing the consistency and reliability of your isolations. Our speakers will also review automation best practices and explain which instruments are the most suited for your laboratory and work style.
Jan-Niklas Schulz, Director Global Product Management, Automated Solutions and 1 more
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2024-11-12T08:00:00Z
Immune checkpoint (IC) blockade and adoptive transfer of tumor-specific T-cells (ACT) are two strategies to treat metastatic melanoma. Their combination can potentiate T-cell activation in the suppressive tumor microenvironment. However, the undesirable autoimmune effects caused by systemic injection of anti-IC remain a major drawback of this strategy. An alternative approach could be the invalidation of ACT of tumor-reactive T-cells for IC expression. For this purpose, PD-1 and TIGIT appear to be relevant candidates because their co-expression identifies highly tumor-reactive lymphocytes but limits their effectiveness within the tumor microenvironment. Using gene editing, we invalidated PDCD1 or TIGIT genes in human Melan-A-specific CD8+ T-cells and first documented the functional consequences on T-cell functions and gene expression. We further compared the anti-tumor properties of wild-type PD-1KO and TIGITKO T-cells in vitro and in a preclinical model of immunodeficient mice, followed by ex-vivo analyses of intra-tumoral T-cell infiltrate. Transcriptomic analyses revealed downregulation of cell cycle-related genes in PD-1KO T-cells, consistent with biological observations, whereas proliferative pathways were preserved in TIGITKO T-cells. Functional analyses showed that PD-1KO and TIGITKO T-cells displayed antitumor reactivity than their wild-type counterparts against targets expressing PD-1 and TIGIT ligands, in vitro and in immunodeficient mice. Consistent with their ability to proliferate in vitro, it appears that TIGITKO T-cell clones were more effective at inhibiting tumor cell proliferation in vivo and persist for up to two weeks after injection within tumors, while PD-1KO T-cell clones were no longer detectable at this time point. Taken together, these results suggest that the deletion of TIGIT in melanoma-specific T lymphocytes constitutes a valuable option for future strategies, while the consequences of PDCD1 editing on T-cell fitness could limit their in vivo persistence and anti-tumor potential.
Nathalie Labarrière, Inserm Research Director and 1 more -
2024-11-12T18:00:00Z
Immune checkpoint (IC) blockade and adoptive transfer of tumor-specific T-cells (ACT) are two strategies to treat metastatic melanoma. Their combination can potentiate T-cell activation in the suppressive tumor microenvironment. However, the undesirable autoimmune effects caused by systemic injection of anti-IC remain a major drawback of this strategy. An alternative approach could be the invalidation of ACT of tumor-reactive T-cells for IC expression. For this purpose, PD-1 and TIGIT appear to be relevant candidates because their co-expression identifies highly tumor-reactive lymphocytes but limits their effectiveness within the tumor microenvironment. Using gene editing, we invalidated PDCD1 or TIGIT genes in human Melan-A-specific CD8+ T-cells and first documented the functional consequences on T-cell functions and gene expression. We further compared the anti-tumor properties of wild-type PD-1KO and TIGITKO T-cells in vitro and in a preclinical model of immunodeficient mice, followed by ex-vivo analyses of intra-tumoral T-cell infiltrate. Transcriptomic analyses revealed downregulation of cell cycle-related genes in PD-1KO T-cells, consistent with biological observations, whereas proliferative pathways were preserved in TIGITKO T-cells. Functional analyses showed that PD-1KO and TIGITKO T-cells displayed antitumor reactivity than their wild-type counterparts against targets expressing PD-1 and TIGIT ligands, in vitro and in immunodeficient mice. Consistent with their ability to proliferate in vitro, it appears that TIGITKO T-cell clones were more effective at inhibiting tumor cell proliferation in vivo and persist for up to two weeks after injection within tumors, while PD-1KO T-cell clones were no longer detectable at this time point. Taken together, these results suggest that the deletion of TIGIT in melanoma-specific T lymphocytes constitutes a valuable option for future strategies, while the consequences of PDCD1 editing on T-cell fitness could limit their in vivo persistence and anti-tumor potential.
Nathalie Labarrière, Inserm Research Director and 1 more
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2024-11-13T08:00:00Z
Non-classical neoantigens from fusion junctions of chimeric RNAs are novel targets for tumor-specific personalized vaccines with low risk of autoimmunity. We present a platform to discover immunogenic neoantigens driving CD8+ T-cell clonotypes from chimeric RNA fusion junctions, with the aim of promoting tumor-reactive T-cell expansion. RNA sequencing data from 1315 patient-derived xenograft (PDX) models harboring 28 different cancer types were analyzed for chimeric RNA. The CD74 [Exon 1-6] | NRG1 [Exon 5-12] fusion was selected based on its established role as an actionable cancer driver and its presence in 4 PDX models with a consistent fusion junction.
We assessed the affinity of 9,10,11mer neopeptides from the CD74-NRG1 fusion to MHC Class I molecules using in silico tools and confirmed these findings in vitro using flow cytometry analyses. Predicted binders were further modeled and ranked by structural features with APEGEN 2.0. Immunogenicity was evaluated via IFN-γ ELISpot assays using HLA-B*07:02-matched PBMCs. Dextramers conjugated with the feature barcode technology were utilized for single-cell 5’ gene expression RNA sequencing and T-cell receptor mapping of antigen-specific activated T cells. This study demonstrates a robust pipeline for identifying immunogenic neoantigens from chimeric RNAs, offering the potential for designing personalized cancer vaccines.
Sakuni Rankothgedera, Lead Scientist -
2024-11-13T18:00:00Z
Non-classical neoantigens from fusion junctions of chimeric RNAs are novel targets for tumor-specific personalized vaccines with low risk of autoimmunity. We present a platform to discover immunogenic neoantigens driving CD8+ T-cell clonotypes from chimeric RNA fusion junctions, with the aim of promoting tumor-reactive T-cell expansion. RNA sequencing data from 1315 patient-derived xenograft (PDX) models harboring 28 different cancer types were analyzed for chimeric RNA. The CD74 [Exon 1-6] | NRG1 [Exon 5-12] fusion was selected based on its established role as an actionable cancer driver and its presence in 4 PDX models with a consistent fusion junction.
We assessed the affinity of 9,10,11mer neopeptides from the CD74-NRG1 fusion to MHC Class I molecules using in silico tools and confirmed these findings in vitro using flow cytometry analyses. Predicted binders were further modeled and ranked by structural features with APEGEN 2.0. Immunogenicity was evaluated via IFN-γ ELISpot assays using HLA-B*07:02-matched PBMCs. Dextramers conjugated with the feature barcode technology were utilized for single-cell 5’ gene expression RNA sequencing and T-cell receptor mapping of antigen-specific activated T cells. This study demonstrates a robust pipeline for identifying immunogenic neoantigens from chimeric RNAs, offering the potential for designing personalized cancer vaccines.
Sakuni Rankothgedera, Lead Scientist
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2024-11-14T08:00:00Z
Lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC) together account for ~15% of all cancer mortalities. Both LUAD and PDAC are commonly driven by KRAS mutations. The first allele-specific KRAS inhibitors were recently approved for LUAD, but clinical benefit is limited by intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative alveolar stem cells by self-renewing and replacing alveolar type 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts and patient samples, we found inhibition of KRAS promotes transition to a quiescent AT1-like cancer cell state in LUAD tumors. Similarly, suppressing KRAS-induced AT1 differentiation of wild-type AT2 cells upon lung injury. The AT1-like LUAD cells exhibited high growth and differentiation potential upon treatment cessation, whereas ablation of the AT1-like cells robustly improved treatment response to KRAS inhibitors. Intra-tumoral heterogeneity in PDAC is characterized by a balance between basal and classical epithelial cancer cell states, with basal dominance associated with chemoresistance and a dismal prognosis. Using genetically engineered mouse models and patient-derived xenografts, we found that basal PDAC cells are highly sensitive to KRAS inhibitors. Employing fluorescent and bioluminescent reporter systems, we longitudinally tracked cell-state dynamics in vivo and revealed a rapid KRAS inhibitor-induced enrichment of the classical state. Lineage tracing identified these enriched classical PDAC cells as reservoirs for disease relapse. Genetic ablation of the classical cell state is synergistic with KRAS inhibition, providing a pre-clinical proof-of-concept for this strategy. Our results uncover an unexpected role of KRAS in promoting intra-tumoral heterogeneity and suggest targeting alveolar or classical epithelial differentiation may augment KRAS-targeted therapies in LUAD and PDAC, respectively.
Tuomas Tammela, Associate Member, Cancer Biology & Genetics Program -
2024-11-14T18:00:00Z
Lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC) together account for ~15% of all cancer mortalities. Both LUAD and PDAC are commonly driven by KRAS mutations. The first allele-specific KRAS inhibitors were recently approved for LUAD, but clinical benefit is limited by intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative alveolar stem cells by self-renewing and replacing alveolar type 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts and patient samples, we found inhibition of KRAS promotes transition to a quiescent AT1-like cancer cell state in LUAD tumors. Similarly, suppressing KRAS-induced AT1 differentiation of wild-type AT2 cells upon lung injury. The AT1-like LUAD cells exhibited high growth and differentiation potential upon treatment cessation, whereas ablation of the AT1-like cells robustly improved treatment response to KRAS inhibitors. Intra-tumoral heterogeneity in PDAC is characterized by a balance between basal and classical epithelial cancer cell states, with basal dominance associated with chemoresistance and a dismal prognosis. Using genetically engineered mouse models and patient-derived xenografts, we found that basal PDAC cells are highly sensitive to KRAS inhibitors. Employing fluorescent and bioluminescent reporter systems, we longitudinally tracked cell-state dynamics in vivo and revealed a rapid KRAS inhibitor-induced enrichment of the classical state. Lineage tracing identified these enriched classical PDAC cells as reservoirs for disease relapse. Genetic ablation of the classical cell state is synergistic with KRAS inhibition, providing a pre-clinical proof-of-concept for this strategy. Our results uncover an unexpected role of KRAS in promoting intra-tumoral heterogeneity and suggest targeting alveolar or classical epithelial differentiation may augment KRAS-targeted therapies in LUAD and PDAC, respectively.
Tuomas Tammela, Associate Member, Cancer Biology & Genetics Program
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2024-11-18T16:00:00Z
Advancements in next-generation sequencing (NGS) have transformed transcriptome and small RNA profiling, enabling gene expression studies and the identification of splice variants, isoforms and novel transcripts from challenging samples like liquid biopsies, FFPE tumors and exosomes. This enhances our understanding of molecular mechanisms and aids in identifying RNA variants as potential disease biomarkers.
In this webinar, we will explore a complete workflow for miRNA biomarker discovery and verification using NGS and digital PCR (dPCR).
Learning objectives
- Set up for miRNA-seq success: Considerations for sample extraction and library preparation for miRNA-seq projects
- Analyzing your data: Bioinformatic pipeline for analysis
- dPCR assay design: How to leverage sequencing data to verify and design sensitive miRNA biomarker assays by dPCR
- Best practices for sequencing projects: Tips for engaging with sequencing cores
Samuel Rulli, Ph.D., Director, Global Product Management, RNA-seq profiling, NGS assay technologies
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2024-11-21T18:00:00Z
When developing your own master mix, choosing between different options for Hot Start Taq Polymerases and Reverse Transcriptases can be daunting. From endpoint PCR to multiplex PCR, you can accelerate your assay development process and save time by minimizing trial and error using trusted and proven products from QIAGEN.
In this webinar, let’s break down the key features and differentiators you should look out for when evaluating which DNA Taq Polymerases and Reverse Transcriptases are best suited for your molecular assay.
Got other plans? You can still register and we’ll send you a link to the recorded webinar.
Anna Sobczak, Global Product Manager, Strategic Marketing, OEM and 1 more -
2024-11-21T08:00:00Z
When developing your own master mix, choosing between different options for Hot Start Taq Polymerases and Reverse Transcriptases can be daunting. From endpoint PCR to multiplex PCR, you can accelerate your assay development process and save time by minimizing trial and error using trusted and proven products from QIAGEN.
In this webinar, let’s break down the key features and differentiators you should look out for when evaluating which DNA Taq Polymerases and Reverse Transcriptases are best suited for your molecular assay.
Got other plans? You can still register and we’ll send you a link to the recorded webinar.
Anna Sobczak, Global Product Manager, Strategic Marketing, OEM and 1 more