A5040160117- Thyroid Cancer Diagnosis and Treatment
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Lipid metabolism and disorders
- Animal Genetics and Reproduction
- Single-cell and spatial transcriptomics
- Biological Research and Disease Studies
- Nutrition, Genetics, and Disease
- Chronic Lymphocytic Leukemia Research
- CRISPR and Genetic Engineering
- Cancer Cells and Metastasis
- Ferroptosis and cancer prognosis
- Epigenetics and DNA Methylation
- Renal Diseases and Glomerulopathies
- Protein Degradation and Inhibitors
- Pancreatic and Hepatic Oncology Research
- Bioinformatics and Genomic Networks
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Chronic Myeloid Leukemia Treatments
University Hospital Heidelberg
2020-2023
Heidelberg University
2019-2023
Spanish National Cancer Research Centre
2015-2023
RWTH Aachen University
2020-2023
Joint Research Centre
2021-2023
Universitätsklinikum Aachen
2020
Centro de Investigación del Cáncer
2015-2018
Bioinformatics Institute
2017
Instituto de Investigaciones Biomédicas Sols-Morreale
2015
Universidad Autónoma de Madrid
2015
Abstract Background Many functional analysis tools have been developed to extract and mechanistic insight from bulk transcriptome data. With the advent of single-cell RNA sequencing (scRNA-seq), it is in principle possible do such an for single cells. However, scRNA-seq data has characteristics as drop-out events low library sizes. It thus not clear if TF pathway established can be applied a meaningful way. Results To address this question, we perform benchmark studies on simulated real We...
Abstract Somatic mutations in calreticulin (CALR) are present approximately 40% of patients with myeloproliferative neoplasms (MPN), but the mechanism by which mutant CALR is oncogenic remains unclear. Here, we demonstrate that expression alone sufficient to engender MPN mice and recapitulates disease phenotype CALR-mutant MPN. We further show thrombopoietin receptor MPL required for CALR-driven transformation through JAK–STAT pathway activation, thus rendering CALR-transformed hematopoietic...
Abstract The presence of differentiated thyroid cells in cancer is critical for the antitumor response to radioactive iodide treatment, and loss phenotype a key hallmark iodide-refractory metastatic disease. role microRNAs (miRNA) fine-tuning gene expression has become major regulatory mechanism by which developmental pathologic processes occur. In this study, we performed next-generation sequencing analysis eight papillary carcinomas (PTC) comprehensively characterize miRNAs involved...
Large-sequencing cancer genome projects have shown that tumors thousands of molecular alterations and their frequency is highly heterogeneous. In such scenarios, physicians oncologists routinely face lists genomic where only a minority them are relevant biomarkers to drive clinical decision-making. For this reason, the medical community agrees on urgent need methodologies establish relevance tumor alterations, assisting in profile interpretation, and, more importantly, prioritize those could...
Understanding why certain patients with IgA nephropathy progress to kidney failure while others maintain normal function remains a major unanswered question. To help answer this, we performed miRNome profiling by next generation sequencing of biopsies in order identify microRNAs specifically associated the risk progression. Following and validation independent cohorts, four (-150-5p, -155-5p, -146b-5p, -135a-5p) were found be differentially expressed progressors compared non-progressors,...
Abstract Multiple sclerosis (MS) is a multifocal and progressive inflammatory disease of the central nervous system (CNS). However, compartmentalized pathology affecting various anatomical regions including gray white matter lack appropriate models impede understanding disease. Utilizing single-nucleus RNA-sequencing multiplex spatial RNA mapping, we generated an integrated transcriptomic map comprising leukocortical, cerebellar spinal cord areas in normal MS tissues that captures regional...
MicroRNA deregulation could be a crucial event in thyroid carcinogenesis. However, current knowledge is based on studies that have used inherently biased methods. Thus, we aimed to define an unbiased way list of deregulated microRNAs well-differentiated cancer order identify diagnostic and prognostic markers. We performed microRNA deep-sequencing study using the largest tumor collection reported date, comprising 127 molecularly characterized tumors with follicular or papillary patterns...
Metastasis development is the leading cause of cancer-related mortality in pancreatic ductal adenocarcinoma (PDAC) and yet, few preclinical systems to recapitulate its full spreading process are available. Thus, modeling tumor progression metastasis urgently needed. In this work, we describe generation highly metastatic PDAC patient-derived xenograft (PDX) mouse models subsequent single-cell RNA-sequencing (RNA-seq) circulating cells (CTC), isolated by human HLA sorting, identify altered...
This study aims to identify sex-specific transcriptional differences and signaling pathways in circulating monocytes contributing cardiovascular disease.We generated sex-biased gene expression signatures by comparing male versus female of coronary artery disease (CAD) patients (n = 450) from the Center for Translational Molecular Medicine-Circulating Cells Cohort. Gene set enrichment analysis demonstrated that CAD carry stronger chemotaxis migratory signature than those males. We then...
Purpose: Medullary thyroid carcinoma (MTC) is a rare disease with few genetic drivers, and the etiology specific to each known susceptibility mutation remains unknown. Exploiting multilayer genomic data, we focused our interest on role of aberrant DNA methylation in MTC development.Experimental Design: We performed genome-wide profiling assessing more than 27,000 CpGs largest series reported date, comprising 48 molecularly characterized tumors. mRNA miRNA expression data were available for...
Atherosclerotic plaque hypoxia is detrimental for macrophage function. Prolyl hydroxylases (PHDs) initiate cellular hypoxic responses, possibly influencing function in hypoxia. Thus, we aimed to elucidate the role of myeloid PHDs atherosclerosis.Myeloid-specific PHD knockout (PHDko) mice were obtained via bone marrow transplantation (PHD1ko, PHD3ko) or conditional knockdown through lysozyme M-driven Cre recombinase (PHD2cko). Mice fed high cholesterol diet 6-12 weeks induce atherosclerosis....
Abstract Glioblastoma (GBM) is the most frequent and aggressive primary tumor type in central nervous system adults. Resistance to chemotherapy remains one of major obstacles GBM treatment. Identifying overcoming mechanisms therapy resistance instrumental develop novel therapeutic approaches for patients with GBM. To determine drivers temozolomide (TMZ) sensitivity, we performed shRNA screenings lines different O6-methylguanine-DNA methyl-transferase (MGMT) status. We then evaluated...
Genetic alterations lead to tumor progression and cell survival but also uncover cancer-specific vulnerabilities on gene dependencies that can be therapeutically exploited.vulcanSpot is a novel computational approach implemented expand the therapeutic options in cancer beyond known-driver genes unlocking alternative ways target undruggable genes. The method integrates genome-wide information provided by massive screening experiments detect genetic associated tumors. Then, vulcanSpot...
The protein 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a key stimulator of glycolytic flux. Systemic, partial PFKFB3 inhibition previously decreased total plaque burden and increased stability. However, it unclear which cell type conferred these positive effects. Myeloid cells play an important role in atherogenesis, mainly rely on glycolysis for energy supply. Thus, we studied whether myeloid PFKFB3-mediated Ldlr-/-LysMCre+/-Pfkfb3 fl/fl (Pfkfb3 ) mice confers...
Abstract Chronic lymphocytic leukaemia is the most prevalent in Western countries. It an incurable disease characterized by a highly variable clinical course. ideal model for studying clonal heterogeneity and dynamics during cancer progression, response to therapy and/or relapse because usually develops over several years. Here we report analysis deep sequencing of sequential samples taken at different times from affected organs two patients with 12- 7-year courses, respectively. One...
Abstract The paradigm of personalized medicine is the identification appropriate drug for right patient, using molecular profiles. In Oncology, it well established that anticancer drugs are effective in only a small subset patients. Moreover, many new targeted therapies inhibit specific proteins, and they tumors genetically altered. Consequently, success treatment depends on each individual profile, which priori can be considered as very heterogeneous. Here, we present computational approach...
Abstract So far, there are few preclinical models that can recapitulate the full metastatic process of pancreatic cancer, therefore modeling tumor progression to metastasis is urgently needed. In our laboratory, we established patient-derived cancer xenograft (PDX) ductal adenocarcinoma (PDA) by orthotopic transplantation human specimens into immunodeficient NOD/SCID/IL2λ-receptor null (NSG) mouse. Importantly, these preserve histological and genetic characteristics donor provide successful...