A5017886341- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Osteoarthritis Treatment and Mechanisms
- Cancer Immunotherapy and Biomarkers
- Inflammatory mediators and NSAID effects
- Atherosclerosis and Cardiovascular Diseases
- Cancer-related molecular mechanisms research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Sarcoma Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Bone Tumor Diagnosis and Treatments
- vaccines and immunoinformatics approaches
- Cancer-related gene regulation
- Bone Metabolism and Diseases
- Asthma and respiratory diseases
- Medicinal plant effects and applications
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Computational Drug Discovery Methods
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
Leiden University Medical Center
2013-2024
Providence Portland Medical Center
2019
Loyola University Medical Center
2012-2015
Leiden University
2014-2015
Abstract Background DNA methylation has been recognized as a key mechanism in cell differentiation. Various studies have compared tissues to characterize epigenetically regulated genomic regions, but due differences study design and focus there still is no consensus the annotation of regions predominantly involved tissue-specific methylation. We used new algorithm identify annotate differentially methylated (tDMRs) from Illumina 450k chip data for four peripheral (blood, saliva, buccal swabs...
Abstract Objective To identify novel genes involved in osteoarthritis (OA), by means of a genome‐wide association study. Methods We tested 500,510 single‐nucleotide polymorphisms (SNPs) 1,341 Dutch Caucasian OA cases and 3,496 controls. SNPs associated with at least 2 phenotypes were analyzed 14,938 ∼39,000 Meta‐analyses performed using the program Comprehensive Meta‐analysis, P values <1 × 10 −7 considered significant. Results The C allele rs3815148 on chromosome 7q22 (minor frequency...
Objective Identify gene expression profiles associated with OA processes in articular cartilage and determine pathways changing during the disease process. Methods Genome wide was determined paired samples of affected preserved same joint using microarray analysis for 33 patients RAAK study. Results were replicated independent by RT-qPCR immunohistochemistry. Profiles analyzed online tools DAVID STRING to identify enrichment specific protein-protein interactions. Among 1717 genes that...
Multiplex immunophenotyping technologies are indispensable for a deeper understanding of biological systems. Until recently, high-dimensional cellular analyses implied the loss tissue context as they were mostly performed in single-cell suspensions. The advent imaging mass cytometry introduced possibility to simultaneously detect multitude markers sections. This technique can be applied various sources including snap-frozen and formalin-fixed, paraffin-embedded (FFPE) tissues. However,...
Objective A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development cancer immunotherapies. We unravelled local systemic profiles in patients with colorectal (CRC) by high-dimensional analysis to provide an unbiased characterisation contexture CRC. Design Thirty-six cell markers were simultaneously assessed at single-cell level mass cytometry 35 CRC tissues, 26 tumour-associated lymph nodes, 17 healthy mucosa 19 peripheral blood...
Objectives To elucidate the functional epigenomic landscape of articular cartilage in osteoarthritis (OA) affected knee and hip joints relation to gene expression. Methods Using Illumina Infinium HumanMethylation450 BeadChip arrays, genome-wide DNA methylation was measured 31 preserved lesioned sample pairs (14 knees 17 hips) from patients who underwent a total joint replacement due primary OA. previously published expression data 33 samples, which 13 were overlapping with current dataset,...
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept patients.In phase I study, patients with resected PDAC were included when they no radiologic signs recurrence standard-of-care treatment. Allogeneic tumour...
<h3>Objectives</h3> To investigate how the genetic susceptibility gene <i>DIO2</i> confers risk to osteoarthritis (OA) onset in humans and explore whether counteracting deleterious effect could contribute novel therapeutic approaches. <h3>Methods</h3> Epigenetically regulated expression of was explored by assessing methylation positional CpG-dinucleotides respective OA-affected macroscopically preserved articular cartilage from end-stage OA patients. In a human vitro chondrogenesis model, we...
Genetic variation at the type II deiodinase (D2) gene (DIO2) was previously identified as osteoarthritis (OA) risk factor. To investigate mechanisms possibly underlying this association, we assessed D2 protein in healthy and OA-affected cartilage investigated allelic balance of OA polymorphism rs225014 DIO2 human joints.Immunohistochemical staining performed for D2. We then mRNA within both away from lesion, ligaments subchondral bone. Allelic measured by amount alleles 'C' 'T' intragenic...
Objective To identify osteoarthritis (OA) progression–modulating pathways in articular cartilage and their respective regulatory epigenetic genetic determinants end‐stage disease. Methods Transcriptional activity of CpG was assessed using gene expression data DNA methylation for preserved lesional samples. Disease‐responsive transcriptionally active were identified by means differential between cartilage. Transcriptionally relevant addressed single‐nucleotide polymorphisms (SNPs) proximal to...
<h3>Objective</h3> To identify pathogenic mutations that reveal underlying biological mechanisms driving osteoarthritis (OA). <h3>Methods</h3> Exome sequencing was applied to two distant family members with dominantly inherited early onset primary OA at multiple joint sites chondrocalcinosis (familial generalised osteoarthritis, FOA). Confirmation of occurred by genotyping and linkage analyses across the extended family. The functional effect mutation investigated means a cell-based assay....
Abstract Background The efficacy of checkpoint blockade immunotherapies in colorectal cancer is currently restricted to a minority patients diagnosed with mismatch repair-deficient tumors having high mutation burden. However, this observation does not exclude the existence neoantigen-specific T cells cancers low burden and exploitation their anti-cancer potential for immunotherapy. Therefore, we investigated whether autologous cell responses could also be observed repair-proficient cancers....
Background Expression of CD103 and CD39 has been found to pinpoint tumor-reactive CD8 + T cells in a variety solid cancers. We aimed investigate whether these markers specifically identify neoantigen-specific colorectal cancers (CRCs) with low mutation burden. Experimental design Whole-exome RNA sequencing 11 mismatch repair-proficient (MMR-proficient) CRCs corresponding healthy tissues were performed determine the presence putative neoantigens. In parallel, tumor-infiltrating lymphocytes...
Chordomas are rare cancers from the axial skeleton which present a challenging clinical management with limited treatment options due to their anatomical location. In recent years, few trials demonstrated that chordomas can respond immunotherapy. However, an in-depth portrayal of chordoma immunity and its association parameters is still lacking.
In colorectal cancer (CRC), T-cell checkpoint blockade is only effective in patients diagnosed with mismatch repair-deficient (MMR-d) cancers. However, defects Human Leukocyte Antigen (HLA) class I expression were reported to occur most MMR-d CRCs, which would preclude antigen presentation these tumours, considered essential for the clinical activity of this immunotherapeutic modality. We revisited paradox by characterising HLA two independent cohorts CRC. determined that loss occurred...
Myxofibrosarcoma and undifferentiated soft tissue sarcoma (USTS) are genetically complex sarcomas with distinct morphological features. Treatment typically involves surgery, often combined neoadjuvant chemo- or radiotherapy. To better understand the immunobiology of these its associations treatment response prognosis, we performed transcriptomic immunophenotypic profiling. RNA sequencing was on 13 USTS 10 myxofibrosarcomas immunological profiles were compared data from The Cancer Genome...
To further explore deiodinase iodothyronine type 2 (DIO2) as a therapeutic target in osteoarthritis (OA) by studying the effects of forced mechanical loading on vivo joint cartilage tissue homeostasis and modulating effect herein Dio2 deficiency.Wild-type C57BL/6-Dio2(-/-) -mice were subjected to running regime for 1 h per day 3 weeks. Severity OA was assessed histological scoring damage synovitis. Genome-wide gene expression determined knee microarray analysis (Illumina MouseWG-6 v2)....
Objective To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute prolonged healthy tissue homeostasis. Methods Previously generated microarray-data (Illumina MouseWG-6 v2) of knee wild-type Dio2 -/- -mice were re-analyzed differential expressed genes independent mechanical loading conditions by forced treadmill-running. RT-qPCR western blot analyses overexpression knockdown Calr mouse...
<p>More detailed information on: 1) Immune-fluorescent staining, 2) Mass spectrometry, 3) MLTC and TIL cultures.</p>