A5062586977- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- vaccines and immunoinformatics approaches
- Cancer-related molecular mechanisms research
- Lymphoma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Cytokine Signaling Pathways and Interactions
- Biochemical and Structural Characterization
- Advanced biosensing and bioanalysis techniques
- Chronic Lymphocytic Leukemia Research
Leiden University Medical Center
2018-2025
Leiden University
2022-2023
Loyola University Medical Center
2022
Stanford University
2009-2021
The Netherlands Cancer Institute
2002-2019
Oncode Institute
2005-2019
California Institute for Regenerative Medicine
2014-2018
Institute for Stem Cell Biology and Regenerative Medicine
2012-2014
Massachusetts Institute of Technology
2013
Harvard–MIT Division of Health Sciences and Technology
2013
CD47, a “don't eat me” signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis patient and matched adjacent normal (nontumor) tissue revealed that CD47 overexpressed cancer mRNA expression levels correlated with decreased probability survival multiple types cancer. ligand SIRPα, protein macrophages dendritic In vitro, blockade signaling using targeted monoclonal antibodies enabled macrophage phagocytosis cells were otherwise protected. Administration...
More diversity at the top A detailed knowledge of cell differentiation hierarchies is important for understanding diverse biological processes such as organ development, tissue regeneration, and cancer. Single-cell RNA sequencing can help elucidate these hierarchies, but it requires reliable computational methods predicting lineage trajectories. Gulati et al. developed CytoTRACE, a framework based on simple observation that transcriptional diversity—the number genes expressed in...
Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2; also known as HER-2/neu), is indicated for the treatment of women with either early stage or metastatic HER2+ breast cancer. It kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Strategies that enhance activity ADCC effectors, NK cells, may improve efficacy trastuzumab. Here, we have shown upon encountering trastuzumab-coated, HER2-overexpressing...
Despite the clinical success of immune checkpoint blockade (ICB), in certain cancer types, most patients with do not respond well. Furthermore, for whom ICB is initially successful, this often short-lived because development resistance to ICB. The mechanisms underlying primary or secondary are incompletely understood. Here, we identified preferential activation and enhanced suppressive capacity regulatory T cells (Treg cells) αPD-L1 therapy-resistant solid tumor-bearing mice. Treg cell...
STAT family members have been implicated in regulating the balance between B cell lymphoma (BCL)6 and lymphocyte induced maturation protein (BLIMP)1 to control plasma differentiation. We previously showed that STAT5 induces BCL6 block differentiation extend life span of human cells. The heterogeneity activation by cytokines their effects on prompted us investigate effect STAT3 First stimulation with IL-21, which promotes differentiation, robust prolonged primary then investigated direct...
MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. We previously reported that miR-142 miR-150 upregulated in human breast cancer cells (BCSCs) as compared to the non-tumorigenic cells. In this study, we report efficiently recruits APC mRNA an RNA-induced silencing complex, activates canonical WNT signaling pathway APC-suppression dependent manner, expression miR-150. Enforced or normal mouse mammary resulted regeneration hyperproliferative glands vivo....
Normal stem cells from a variety of tissues display unique metabolic properties compared to their more differentiated progeny. However, relatively little is known about cancer cells, also called tumor initiating (TICs). In this study we show that, analogous some normal breast TICs have distinct nontumorigenic (NTCs). Transcriptome profiling using RNA-Seq revealed underexpress genes involved in mitochondrial biology and oxidative phosphorylation, analyses preferentially perform glycolysis...
Nonresolving chronic inflammation at the neoplastic site is consistently associated with promoting tumor progression and poor patient outcomes. However, many aspects behind mechanisms that establish this tumor-promoting inflammatory microenvironment remain undefined. Using bladder cancer (BC) as a model, we found CD14-high cells express higher levels of numerous mediators form larger tumors compared CD14-low cells. CD14 antigen glycosyl-phosphatidylinositol (GPI)-linked glycoprotein has been...
Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass this checkpoint. Using retroviral cDNA expression libraries, we BCL6 as potent inhibitor senescence. is frequently activated non-Hodgkin's lymphoma, but its mechanism action has remained unclear. efficiently immortalizes mouse embryonic fibroblasts and cooperates with RAS oncogenic transformation. overrides senescence response downstream p53 through...
IgM+IgD+CD27+ B cells from peripheral blood have been described as circulating marginal zone cells. It is still unknown when and where these develop. These exhibit somatic hypermutations (SHMs) in their cell receptors, but the exact nature of signals leading to induction SHMs remains elusive. Here, we show that carrying are observed during human fetal development. To examine role T development used an vivo model which Rag2−/−γC−/− mice were repopulated with hematopoietic stem Using on a Nude...
T-cell mediated immunotherapy brought clinical success for many cancer patients. Nonetheless, downregulation of MHC class I antigen presentation, frequently occurring in solid cancers, limits the efficacy these therapies. Unraveling mechanisms underlying this type immune escape is therefore great importance. We here investigated immunological effects metabolic stress cells as a result nutrient deprivation.TC1 and B16F10 tumor cell lines were cultured under oxygen- glucose-deprivation...
Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL-7-receptor-alpha chain and unique TSLP receptor (TSLPR) chain. The role of in human B-cell development has not been elucidated. We show TSLPR transcripts are expressed most prominently CD34(+) cells from fetal liver BM. In general, cell surface expression was low, except on subset multilineage-commited progenitor cells. induced tyrosine-phosphorylation STAT5 proliferation cells, pro-B pre-B Compared with IL-7, levels after...