A5091460068- IgG4-Related and Inflammatory Diseases
- Cancer Genomics and Diagnostics
- Neuroendocrine Tumor Research Advances
- Sarcoma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Wildlife Ecology and Conservation
- Environmental DNA in Biodiversity Studies
- Gastrointestinal Tumor Research and Treatment
- Ferroptosis and cancer prognosis
- Eosinophilic Disorders and Syndromes
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- Renal cell carcinoma treatment
- Cancer Cells and Metastasis
- Soft tissue tumors and treatment
- Bioinformatics and Genomic Networks
- Mast cells and histamine
- Congenital gastrointestinal and neural anomalies
- Immune cells in cancer
- Asthma and respiratory diseases
- Microtubule and mitosis dynamics
- Ear and Head Tumors
KU Leuven
2019-2025
VIB-KU Leuven Center for Cancer Biology
2019-2023
Vlaams Instituut voor Biotechnologie
2021
Oeko Institut
2017
University of Canberra
2017
Abstract Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment propagation, affecting accuracy of modeling cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 matched patient (PT) samples from 509 models. CNA inferences based on DNA sequencing microarray data displayed substantially higher resolution...
Significance The pituitary is our master endocrine gland. Local damage and aging present important threats. We started to decrypt the ill-defined regulation of gland’s stem cells, typically dormant but acutely activated upon damage. Single-cell transcriptomics uncovered interleukin-6 as a cell activator local damage, corroborated in vivo vitro using cell–derived organoids. This competence extinguishes at aging, concurrent with raised inflammatory state older gland (inflammaging). However,...
T cells dynamically rewire their metabolism during an immune response. We applied single-cell RNA sequencing to CD8+ activated and differentiated in vitro physiological medium resolve these metabolic dynamics. identify a differential time-dependent reliance of activating on the synthesis versus uptake various non-essential amino acids, which we corroborate with functional assays. also genes that potentially dictate outcome cell differentiation, by ranking them based expression Among them,...
ABSTRACT Introduction Postoperative ileus (POI) is an iatrogenic disorder marked by temporary impaired gastrointestinal (GI) motility post‐abdominal surgery. Surgical handling of the intestine activates resident macrophages (Mfs), leading to inflammatory cytokine release and leukocyte recruitment into muscularis , which compromises intestinal contractility. The mechanisms behind this activation are unclear. Recent studies suggest peritoneal Mfs, particularly large (LPMs), might play a role...
Renal Cell Carcinoma (RCC) is difficult to treat with 5-year survival rate of 10% in metastatic patients. Main reasons therapy failure are lack validated biomarkers and scarce knowledge the biological processes occurring during RCC progression. Thus, investigation mechanisms regulating progression fundamental improve therapy.In order identify molecular markers gene involved steps progression, we generated several cell lines higher aggressiveness by serially passaging mouse renal cancer RENCA...
Abstract Purpose: The European Organization for Research and Treatment of Cancer (EORTC) clinical phase II trial 90101 “CREATE” showed high antitumor activity crizotinib, an inhibitor anaplastic lymphoma kinase (ALK)/ROS1, in patients with advanced inflammatory myofibroblastic tumor (IMFT). However, recent findings suggested that other molecular targets addition to ALK/ROS1 might also contribute the sensitivity this inhibitor. We therefore performed in-depth characterization archival IMFT...
Gut mast cells are key players in infection and inflammation, as well homeostasis. Mast regulate gastrointestinal (GI) function by controlling vascular epithelial permeability, interacting with the immune system enteric nervous system. Mucosal (MCT) connective tissue (MCTC) coexist tract, but located distinct microanatomical niches. However, little is known about transcriptional heterogeneity of human intestinal cells. Additionally, whether niches instruct cell phenotypes gut currently...
Identification of species from trace samples is now possible through the comparison diagnostic DNA fragments against reference sequence databases. detection animals non-invasive samples, such as predator faeces (scats) that contain traces their origin, has proved to be a valuable tool for management elusive wildlife. However, application this approach can limited by availability appropriate genetic markers. Scat often degraded, meaning longer sequences, including standard barcoding markers,...
Abstract The ability to detect the incursion of an invasive species or destroy last individuals during eradication program are some most difficult aspects management. presence foxes in Tasmania is a contentious issue with recent structured monitoring efforts, involving collection carnivore scats and testing for fox DNA , failing any evidence foxes. Understanding likelihood that efforts would presence, given at least one present, therefore critical understanding role scat informing response...
Abstract Purpose: A randomized phase III study evaluated the efficacy of eribulin versus dacarbazine in patients with advanced liposarcoma and leiomyosarcoma. Improved overall survival (OS) led to approval for liposarcoma, but not Experimental Design: We explored molecular profile 77 archival leiomyosarcoma samples from this trial identify potential predictive biomarkers, utilizing low-coverage whole-genome whole-exome sequencing. Tumor profiles were correlated clinical data, disease control...
Abstract Purpose: Regorafenib (REG) is approved for the treatment of metastatic colorectal cancer, but has modest survival benefit and associated toxicities. Robust predictive/early response biomarkers to aid patient stratification are outstanding. We have exploited biological pathway analyses in a patient-derived xenograft (PDX) trial study REG mechanisms elucidate putative biomarkers. Experimental Design: Molecularly subtyped PDXs were annotated response. Subtyping was based on gene...
Clear cell sarcoma (CCSA) is characterized by a chromosomal translocation leading to EWSR1 rearrangement, resulting in aberrant transcription of multiple genes, including MET. The EORTC 90101 phase II trial evaluated the MET inhibitor crizotinib CCSA but resulted only sporadic responses. We performed an in-depth histopathological and molecular analysis archival samples identify alterations potentially relevant for treatment outcome. Immunohistochemical characterization signaling was using...
ABSTRACT Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment propagation, impacting accuracy of modeling cancer. Here we exhaustively analyze copy number alterations (CNAs) in 1451 matched patient (PT) samples from 509 models. CNA inferences based on DNA sequencing microarray data displayed substantially higher resolution dynamic...
Alveolar soft part sarcoma (ASPS) is a rare subtype of tissue characterized by an unbalanced translocation, resulting in ASPSCR1-TFE3 fusion that transcriptionally upregulates MET expression. The European Organization for Research and Treatment Cancer (EORTC) 90101 "CREATE" phase II trial evaluated the inhibitor crizotinib ASPS patients, achieving only limited antitumor activity. We performed comprehensive molecular analysis samples collected this to identify potential biomarkers correlating...
Summary Correct development and maturation of the enteric nervous system (ENS) is critical for survival. Early in life, ENS requires significant refinement order to adapt evolving needs tissue, changing from milk solid food at time weaning. Here, we demonstrate that resident macrophages muscularis externa, MMϕ, refine early life by pruning synapses phagocytosing abundant neurons. After weaning, MMϕ continue closely interact with ENS, acquire a microglia-like phenotype are crucial survival Of...
A Correction to this paper has been published: https://doi.org/10.1038/s41588-021-00811-4.
ABSTRACT Cytotoxic T cells dynamically rewire their metabolism during the course of an immune response. While T-cell has been extensively studied at phenotypic endpoints activation and differentiation, underlying dynamics remain largely elusive. Here, we leverage on single-cell RNA-sequencing (scRNA-seq) measurements in vitro activated differentiated CD8 + cultured physiological media to resolve these metabolic dynamics. We find that our scRNA-seq analysis identifies most changes previously...
<p>Example of CNA profiles obtained in LMS. Copy-number plots: x-axis represents the position on full genome (chromosome numbers are indicated). Red dots represent normalized read count for bins 50Kb (log R value). Y-values around 0 copy-number (CN) 2 (grey line). Lower values indicate a deletion and higher gain. The horizontal green line segmented CN profiles</p>
<p>Supplementary Figures S1 - S8 and Table S1. Fig S1: Analysis of copy number burden in a PDX population trial REG treated mCRC PDXs. S2: Effect on microvessel density proliferation according to CNA cluster. S3 S6: BCL-2 family profiling models via quantitative Western blotting. S7: RPPA protein scores indicating proteins' association with the models' response REG. S8: blot validation differential EPHA2 expression between post- pre-treatment progressor non-progressor models. List...