Francis Jacob
A5040470585- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Ovarian cancer diagnosis and treatment
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Metalloenzymes and iron-sulfur proteins
- Cancer-related gene regulation
- Galectins and Cancer Biology
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- Cerebrovascular and genetic disorders
- Cell Adhesion Molecules Research
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- Cell Image Analysis Techniques
- DNA Repair Mechanisms
- Advanced Proteomics Techniques and Applications
- Cancer-related molecular mechanisms research
University of Basel
2016-2025
University Hospital of Basel
2016-2025
UNSW Sydney
2012-2015
Hospital Base
2014-2015
Friedrich-Loeffler-Institut
2013-2014
Cancer Australia
2014
University Hospital of Zurich
2011-2013
TU Dresden
2007-2009
Centre Hospitalier de Luxembourg
1993
Immune checkpoint blockade (ICB) has substantially improved the prognosis of patients with cancer, but majority experiences limited benefit, supporting need for new therapeutic approaches. Up-regulation sialic acid–containing glycans, termed hypersialylation, is a common feature cancer-associated glycosylation, driving disease progression and immune escape through engagement Siglec receptors on tumor-infiltrating cells. Here, we show that tumor sialylation correlates distinct states reduced...
Abstract Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients cancer, reflecting their contribution to the development tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates varying degrees organization and maturation. Specifically, mature TLSs (mTLS) as forming only 16% HGSOCs relatively elevated tumor mutational burden (TMB) are an increased...
Abstract Expression of two Arabidopsis (Arabidopsis thaliana) apyrase (nucleoside triphosphate-diphosphohydrolase) genes with high similarity, APY1 and APY2, was analyzed during seedling development under different light treatments using β-glucuronidase fusion constructs the promoters both genes. As evaluated by staining independently confirmed other methods, highest expression apyrases in rapidly growing tissues and/or that accumulate auxin levels. Red-light treatment etiolated seedlings...
Epithelial ovarian cancer is the fifth most common cause of in women worldwide bearing highest mortality rate among all gynecological cancers. Cell membrane glycans mediate various cellular processes such as cell signaling and become altered during carcinogenesis. The extent to which glycosylation changes are influenced by aberrant regulation gene expression nearly unknown for remains crucial understanding development progression this disease. To address effect, we analyzed non-cancerous...
The molecular repertoire promoting cancer cell plasticity is not fully elucidated. Here, we propose that glycosphingolipids (GSLs), specifically the globo and ganglio series, correlate promote transition between epithelial mesenchymal cells. character of ovarian remains stable throughout disease progression, spatial glycosphingolipidomics reveals elevated globosides in tumor compartment compared with ganglioside-rich stroma. CRISPR-Cas9 knockin mediated truncation endogenous E-cadherin...
Recent technological advances have led to an increase in the production and availability of single-cell data. The ability integrate a set multi-technology measurements would allow identification biologically or clinically meaningful observations through unification perspectives afforded by each technology. In most cases, however, profiling technologies consume used cells thus pairwise correspondences between datasets are lost. Due sheer size can acquire, scalable algorithms that able...
The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset peritoneal cavity remains unexplored. Here, we suggest a new route metastasis through interaction integrin alpha 2 (ITGA2) with collagens enriched coinciding poor outcome patients ovarian cancer. Using multiple gene-edited cell lines patient-derived samples, demonstrate that ITGA2 triggers cancer adhesion collagen, promotes migration,...
Understanding the complex background of cancer requires genotype-phenotype information in single-cell resolution. Here, we perform long-read RNA sequencing (scRNA-seq) on clinical samples from three ovarian patients presenting with omental metastasis and increase PacBio depth to 12,000 reads per cell. Our approach captures 152,000 isoforms, which over 52,000 were not previously reported. Isoform-level analysis accounting for non-coding isoforms reveals 20% overestimation protein-coding gene...
In cancer, genetic and transcriptomic variations generate clonal heterogeneity, leading to treatment resistance. Long-read single-cell RNA sequencing (LR scRNA-seq) has the potential detect simultaneously. Here, we present LongSom, a computational workflow leveraging high-quality LR scRNA-seq data call de novo somatic single-nucleotide variants (SNVs), including in mitochondria (mtSNVs), copy number alterations (CNAs), gene fusions, reconstruct tumor heterogeneity. Before variant calling,...
Abstract Epithelial ovarian cancer has the highest mortality rate among gynecological cancers. Altered glycosylation is associated with oncogenic transformation producing tumor‐associated carbohydrate antigens. We investigated potential of natural occurring antiglycan antibodies in diagnosis by using printed glycan array. Antiglycan bound to 203 chemically synthesized glycans were detected via biotin‐streptavidin fluorescence system serum women normal operative findings (healthy controls; n...
ObjectiveMaternal embryonic leucine-zipper kinase (MELK) shows oncogenic properties in basal-like breast cancer, a cancer subtype sharing common molecular features with high-grade serous ovarian cancer. We examined the potential of MELK as and pharmacological target for treatment epithelial (EOC).Methods/materialsBioinformatic analysis was performed on nine OC transcriptomic data sets totaling 1241 patients. Effects depletion by shRNA or inhibition OTSSP167 cell lines were assessed colony...
Abstract Peritoneal dissemination is a particular form of metastasis typically observed in ovarian cancer and the major cause for poor patient’s outcome. Identification molecular players involved can offer an approach to develop treatment strategies improve clinical prognosis. Here, we identified mesothelin (MSLN) as crucial protein multistep process peritoneal cancer. We demonstrated that MSLN overexpressed primary matched high-grade serous carcinomas (HGSC). Using several genetically...
<p>NACT-mediated adjuvanticity positively impacts the density of follicular T cells (T<sub>FH</sub>) and <i>in situ</i> activation intratumoral B in mHGSOC. <b>A–C,</b> Representative image (<b>A</b>) box plots showing CD4<sup>+</sup> (<b>B</b>) CXCR5<sup>+</sup>PD1<sup>+</sup>FoxP3<sup>−</sup>CD4<sup>+</sup> T<sub>FH</sub> (<b>C</b>) pTME mTME...
<p>NACT-mediated adjuvanticity positively impacts clinically relevant TLS maturation in metastatic HGSOC. <b>A,</b> Representative image of immunofluorescence CD4, CD8, CD20, CD21, CD23, DC-LAMP, and GZMB staining (immunofluorescence panel 1). Scale bars, 10, 100 500 µm. <b>B</b> <b>C,</b> Distribution early (eTLS; <b>B</b>) mature (mTLS; <b>C</b>) across pTME mTME HGSOC tumor samples with/without NACT. Statistical...
<p>NACT-mediated progenitor TCF1<sup>+</sup>PD1<sup>+</sup>CD8<sup>+</sup> T-cell phenotype associates with effector cytotoxic functions within metastatic HGSOC. <b>A–C,</b> Representative dot plot (<b>A</b>) and box (<b>B</b>) showing percentage of TIM-3<sup>+</sup>PD1<sup>+</sup>CD8<sup>+</sup> T cells GZMB<sup>+</sup>CD8<sup>+</sup> native pTME mTME...
<div>AbstractPurpose:<p>Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of effector cells HGSOC microenvironment stand out promising combinatorial partners for ICIs...
<p>Supplemental material, figures and tables</p>
<p>NACT positively increases the ICI-sensitive TCF1<sup>+</sup>PD1<sup>+</sup>CD8<sup>+</sup> T-cell phenotype within metastatic HGSOC. <b>A,</b> Representative image of immunofluorescence CD68, CD8, PD-L1, FoxP3, TCF1, CD57, PanCK, PD1, CD4, CD20, GZMB, and TIM-3 staining (immunofluorescence panel 2). Scale bars, 2 μm, 10 µm, 100 µm. <b>B,</b> Violin plot showing density CD8<sup>+</sup>...
<p>The clinical relevance of combined chemotherapy and immunotherapy in mouse models TMB<sup>Lo</sup> TMB<sup>Hi</sup> ovarian cancer. <b>A</b> <b>B,</b> Bar plots showing single-nucleotide variants positions (SNVs) (<b>A</b>) the somatic mutations prevalence (mutations per megabase) (<b>B</b>) ID8 (<i>n</i> = 3)...