A5039561628- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- HIV/AIDS Impact and Responses
- Molecular Biology Techniques and Applications
- BRCA gene mutations in cancer
- Bioinformatics and Genomic Networks
- MicroRNA in disease regulation
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Breast Cancer Treatment Studies
- RNA Research and Splicing
- Neuropeptides and Animal Physiology
- Genomic variations and chromosomal abnormalities
The Netherlands Cancer Institute
2015-2024
Cancer Genomics Centre
2013-2023
The University of Texas MD Anderson Cancer Center
2019
Oncode Institute
2013
University Medical Center
2013
École Nationale Supérieure des Mines de Paris
2012
Institut Curie
2012
Inserm
2012
Centre National de la Recherche Scientifique
2012
Inria Saclay - Île de France
2012
The evidence for T-cell–mediated regression of human cancers such as non–small-cell lung carcinoma, renal cell and—in particular—melanoma after immunotherapy is strong. Anti-CTLA4 (ipilimumab) treatment has been approved meta-static melanoma,1 and antibody-mediated blockade PD-1, a second inhibitory receptor on T cells, shown highly encouraging results in early clinical trials.2,3 Although the activity these treatments apparent, it still unknown which T-cell reactivities are involved...
Women carrying germ-line mutations in BRCA1 are strongly predisposed to developing breast cancers with characteristic features also observed sporadic basal-like cancers. They appear as high-grade tumors high proliferation rates and pushing borders. On the molecular level, they negative for hormone receptors ERBB2, display frequent TP53 mutations, express basal epithelial markers. To study role of P53 loss function cancer development, we generated conditional mouse models tissue-specific...
DNA topoisomerase II inhibitors are a major class of cancer chemotherapeutics, which thought to eliminate cells by inducing double-strand breaks. Here we identify novel activity for the anthracycline inhibitors: histone eviction from open chromosomal areas. We show that anthracyclines promote irrespective their ability induce The variant H2AX, is key component damage response, also evicted anthracyclines, and H2AX associated with attenuated repair. Histone deregulates transcriptome in organs...
Glycosylated α-dystroglycan (α-DG) serves as cellular entry receptor for multiple pathogens, and defects in its glycosylation cause hereditary Walker-Warburg syndrome (WWS). At least eight proteins are critical to glycosylate α-DG, but many genes mutated WWS remain unknown. To identify modifiers of we performed a haploid screen Lassa virus entry, hemorrhagic fever causing thousands deaths annually that hijacks glycosylated α-DG enter cells. In complementary screens, profiled cells absence...
Abstract Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function heterogeneity, little is known regarding origin CAFs. Understanding CAF heterogeneity needed to develop successful CAF-based targeted therapies. Through various transplantation studies mice, we show that CAFs both invasive lobular breast cancer triple-negative originate from mammary...
Abstract Despite their low abundance in the tumor microenvironment (TME), classical type 1 dendritic cells (cDC1) play a pivotal role anti-cancer immunity, and positively correlates with patient survival. However, interaction CD4 + T-cells to potentially enable cytotoxic T lymphocyte (CTL) response has not been elucidated. Here we show that contact activated enables human ex vivo cDC1, but no other DC types, induce CTL cell-associated antigens. Single cell transcriptomics reveals T-cell help...
Cells in the tumor microenvironment (TME) influence each other through secretion and sensing of soluble mediators, such as cytokines chemokines. While signaling interferon γ (IFNγ) necrosis factor α (TNFα) is integral to anti-tumor immune responses, our understanding spatiotemporal behavior these limited. Here, we describe a single cell transcriptome-based approach infer which signal(s) an individual has received. We demonstrate that, contrary expectations, CD8+ T cell-derived IFNγ dominant...
The E2F family of transcription factors controls the expression genes that are involved in cell cycle regulation. DNA-binding activity is found complex with retinoblastoma protein, pRb, and pRb-related p107 p130. To date, cDNAs for three members gene have been isolated. However, all E2Fs associate vivo exclusively pRb. We report here cloning functional analysis a fourth member. E2F-4 encodes 413-amino-acid protein significant homology to E2F-1. antibodies recognize 60-kD anti-p107...
The orderly progression through the cell cycle is mediated by sequential activation of several cyclin/cyclin-dependent kinase (cdk) complexes. These kinases phosphorylate a number cellular substrates, among which product retinoblastoma gene, pRb. Phosphorylation pRb in late G1 causes release transcription factor E2F from pRb, resulting transcriptional E2F-responsive genes. We show here that phosphorylation pRb-related p107 also regulated. first phosphorylated at 8 hr following serum...
E2F transcription factors are key regulators of during the cell cycle. activity is regulated at level and DNA binding by complex formation with retinoblastoma pocket protein family. We show here that free E2F-1 E2F-4 unstable their degradation mediated ubiquitin-proteasome pathway. Both rendered an epitope in carboxyl terminus proteins, close proximity to interaction surface. pRb or p107 p130 protects E2Fs from degradation, causing complexes be stable. The increased stability may contribute...
The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of development single naive into different subsets, we have developed technology that introduces unique genetic tags (barcodes) cells. By comparing barcodes present in antigen-specific cell populations systemic local infection models, at anatomical sites, for TCR-pMHC interactions avidities, demonstrate under all conditions tested, individual yield both CD8+...
Polycomb group (PcG) proteins bind and regulate hundreds of genes. Previous evidence has suggested that long-range chromatin interactions may contribute to the regulation PcG target Here, we adapted Chromosome Conformation Capture on Chip (4C) assay systematically map chromosomal in Drosophila melanogaster larval brain tissue. Our results demonstrate genes interact extensively with each other nuclear space. These are highly specific for genes, because non-target either low or high expression...
Background and Methods Formalin Fixed Paraffin Embedded (FFPE) samples represent a valuable resource for cancer research. However, the discovery development of new biomarkers often requires fresh frozen (FF) samples. Recently, Whole Genome (WG) DASL (cDNA-mediated Annealing, Selection, extension Ligation) assay was specifically developed to profile FFPE tissue. thorough comparison data generated from RNA Fresh Frozen using this platform is lacking. To end we profiled, in duplicate, 20...