A5015468870- RNA modifications and cancer
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Sarcoma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Chromatin Remodeling and Cancer
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Fungal and yeast genetics research
- Bone Tumor Diagnosis and Treatments
- Ubiquitin and proteasome pathways
- Nuclear Structure and Function
- Cancer, Lipids, and Metabolism
- RNA and protein synthesis mechanisms
- Ovarian cancer diagnosis and treatment
- Cancer Mechanisms and Therapy
- Glioma Diagnosis and Treatment
German Cancer Research Center
2018-2024
Heidelberg University
2018-2024
Hopp Children's Cancer Center Heidelberg
2024
Epigenomics (Germany)
2018-2023
National University of Singapore
2015-2022
National University Cancer Institute, Singapore
2015-2021
Kyoto University
2015
Indian Institute of Science Education and Research Thiruvananthapuram
2014
Virginia Commonwealth University
2011
Cornell University
2006-2007
Numerous large-scale genomic studies of matched tumor-normal samples have established the somatic landscapes most cancer types. However, downstream analysis data from mutations entails a number computational and statistical approaches, requiring usage independent software numerous tools. Here, we describe an R Bioconductor package, Maftools, which offers multitude visualization modules that are commonly used in studies, including driver gene identification, pathway, signature, enrichment,...
Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression function.We studied patterns functions of 4 SCC-specific lncRNAs. obtained 113 esophageal SCC (ESCC) matched non-tumor tissues from a hospital Shantou City, China, performed quantitative reverse transcription polymerase chain reaction assays measure levels...
Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that master transcription factors (TFs) TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. However, functional consequence of their frequent co-localization at super-enhancers remains incompletely understood. Here, epigenomic profilings different types SCCs reveal cooperatively lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation its promoter....
<h3>Objectives</h3> Oesophageal squamous cell carcinoma (OSCC) is an aggressive malignancy and the major histological subtype of oesophageal cancer. Although recent large-scale genomic analysis has improved description genetic abnormalities OSCC, few targetable lesions have been identified, no molecular therapy available. This study aims to identify druggable candidates in this tumour. <h3>Design</h3> High-throughput small-molecule inhibitor screening was performed potent anti-OSCC...
Abstract Understanding the intratumoral heterogeneity of hepatocellular carcinoma is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients resolve genetic architecture subclonal diversification. Spatial genomic diversity was found in all cases, with 29% driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, STAG2. Similar other cancer types, TP53 were always shared between...
Abstract Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known to contain an active-site cysteine residue undergoing oxidation in response hydrogen peroxide, leading rapid inactivation of the enzyme. Here we show that human and mouse cells expressing a GAPDH mutant lacking this redox switch retain catalytic activity but are unable stimulate oxidative pentose phosphate pathway enhance their reductive capacity. Specifically, find anchorage-independent growth spheroids limited by elevation...
Abstract Mutation Annotation Format (MAF) has become a standard file format for storing somatic/germline variants derived from sequencing of large cohort cancer samples. MAF files contain list all detected in sample along with various annotations associated the putative variant. forms basis many downstream analyses and provides complete landscape cohort. Here we introduce maftools–an R package that rich source functions performing analyses, visualizations summarization files. Maftools uses...
Acute promyelocytic leukemia (APL) is a subtype of myeloid characterized by differentiation block at the promyelocyte stage. Besides presence chromosomal rearrangement t(15;17), leading to formation PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis primary and relapse APL identify somatic alterations, which cooperate with pathogenesis We explored landscape...
Liposarcoma (LPS) is the most common type of soft tissue sarcoma accounting for 20% all adult sarcomas. Due to absence clinically effective treatment options in inoperable situations and resistance chemotherapeutics, a critical need exists identify novel therapeutic targets. We analyzed LPS genomic landscape using SNP arrays, whole exome sequencing targeted uncover information development specific anti-cancer array analysis indicated known amplified genes (MDM2, CDK4, HMGA2) important (UAP1,...
Oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) are distinct cancers in terms of a number clinical epidemiological characteristics, complicating the design trials biomarker developments. We analysed 1048 oesophageal tumour-germline pairs from both subtypes, to characterise their genomic features, biological significance.
Significance Glioblastoma (GBM) cells develop intrinsic or acquired insensitiveness to BET bromodomain inhibitors (BBIs) yet persistent protein dependency. Selective degradation of proteins by a next-generation chemical compound undermines the dependency and exerts superior antineoplastic effects over inhibition bromodomain. Given significant difference between in GBM cells, chemically induced serves as promising strategy overcome anticipated clinical BBIs resistance.
ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise of SCC biology remains unclear. In this study, we report that is exclusively deleted, mutated and underexpressed human SCCs, low expression associated with poor survival. Restoration wildtype, but not mutant protein uniquely inhibited malignant phenotypes cells both vitro vivo. Notably, promoted long...
Abstract Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, those involving epigenetic dysregulation, remain largely elusive, hampering clinical management this malignancy. To identify novel druggable targets, we carried out unbiased high-throughput chemical screening observed that NPC cells were highly sensitive to inhibitors cyclin-dependent kinases (CDK), especially THZ1, a covalent...
Abstract Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting ability address resistant tumors or develop less toxic targeted therapies. Here, we report use next-generation sequencing interrogate and pathogenic mechanisms 240 ALL cases their matched samples. Commonly mutated genes fell into several...
ZBTB transcription factors orchestrate gene during tissue development. However, their roles in glioblastoma (GBM) remain unexplored. Here, through a functional screening of genes, we identify that BCL6 is required for GBM cell viability and overexpression associated with worse prognosis. In somatic transgenic mouse model, depletion Bcl6 inhibits the progression KrasG12V-driven high-grade glioma. Transcriptome analysis demonstrates involvement tumor protein p53 (TP53), erythroblastic leukemia...
Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order occurrence MLL-PTD in relation to other major AML mutations and identify novel that may be present this unique molecular subtype, exome targeted sequencing was performed on 85 samples using HiSeq-2000. Genes involved cohesin complex (STAG2), splicing factor (U2AF1) poorly studied gene, MGA were recurrently mutated, whereas NPM1, one most...
Precise regulation of chromatin architecture is vital to physiological processes including hematopoiesis. ARID1A a core component the mammalian SWI/SNF complex, which one ATP-dependent remodeling complexes. To uncover role in hematopoietic development, we utilized cell-specific deletion Arid1a mice. We demonstrate that essential for maintaining frequency and function stem cells its loss impairs differentiation both myeloid lymphoid lineages. deficiency led global reduction open ensuing...
As the second most common malignant bone tumor in children and adolescents, Ewing sarcoma is initiated exacerbated by a chimeric oncoprotein, commonly, EWS-FLI1. In this study, we apply epigenomic analysis to characterize transcription dysregulation cancer, focusing on investigation of super-enhancer its associated transcriptional regulatory mechanisms. We demonstrate that super-enhancer-associated transcripts are significantly enriched EWS-FLI1 target genes, contribute aberrant network...
Abstract Motivation BigWig files serve as essential inputs in epigenomic data visualization. However, current R packages for visualizing these are limited, slow, and burdened by numerous dependencies. Results We introduce trackplot, a minimal script designed the rapid generation of integrative genomics viewer (IGV) style track plots, profile heatmaps from bigWig files. This offers speed, owing to its reliance on bwtool, resulting performance gains several magnitudes compared equivalent...
Purpose: Ewing sarcoma (EWS) is a devastating soft tissue affecting predominantly young individuals. Tyrosine kinases (TK) and associated pathways are continuously activated in many malignancies, including EWS; these enzymes provide candidate therapeutic targets.Experimental Design: Two high-throughput screens (a siRNA library small-molecule inhibitor library) were performed EWS cells to establish targets. Spleen tyrosine kinase (SYK) phosphorylation was assessed patients cell lines. SYK...
Abstract ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved adenylate-uridylate–rich elements (ARE) located in 3′untranslated regions (UTR) to mediate mRNA decay. We hypothesized negative regulator of posttranscriptional hub involved half-life regulation cancer-related transcripts. Analysis silico data revealed was significantly mutated, epigenetically silenced, and downregulated variety cancers. Forced expression cancer cells markedly reduced cell proliferation...
Liposarcomas (LPSs) are a group of malignant mesenchymal tumors showing adipocytic differentiation. Here, to gain insight into the enhancer dysregulation and transcriptional addiction in this disease, we chart super-enhancer structures both LPS tissues cell lines. We identify bromodomain extraterminal (BET) protein-cooperated FUS-DDIT3 function myxoid BET protein-dependent core regulatory circuitry consisting FOSL2, MYC, RUNX1 de-differentiated LPS. Additionally, SNAI2 is identified as...