A5020240649- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Carcinogens and Genotoxicity Assessment
- Plant Pathogens and Resistance
- Mycotoxins in Agriculture and Food
- Chromatin Remodeling and Cancer
- DNA Repair Mechanisms
- Potato Plant Research
- Cancer Research and Treatments
- Ocular Oncology and Treatments
- Heavy Metal Exposure and Toxicity
- Hippo pathway signaling and YAP/TAZ
- Arsenic contamination and mitigation
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Developmental Biology and Gene Regulation
- Biological Research and Disease Studies
- Pesticide Exposure and Toxicity
- Drug-Induced Hepatotoxicity and Protection
- Health, Environment, Cognitive Aging
- Microtubule and mitosis dynamics
- Research on Leishmaniasis Studies
Centre International de Recherche sur le Cancer
2016-2025
Harvard University
2004-2017
Massachusetts General Hospital
2004-2017
Molecular Oncology (United States)
2012-2013
Cancer Research Center
2011-2012
Philipps University of Marburg
2006
Ludwig-Maximilians-Universität München
2003-2005
Center for Cancer Research
2004
Here we report the identification of LIN complex (LINC), a human multiprotein that is required for transcriptional activation G2/sub>/M genes. LINC related to recently identified dREAM and DRM complexes Drosophila C.elegans contain homologues mammalian retinoblastoma tumor suppressor protein. The core consists at least five subunits including chromatin-associated LIN-9 RbAp48 proteins. dynamically associates with pocket proteins, E2F B-MYB during cell cycle. In quiescent cells, binds p130...
Humans are frequently exposed to acrylamide, a probable human carcinogen found in commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer rodents, yet epidemiological studies conducted date limited and, thus far, have yielded inconclusive data on association of cancers with exposure. In this study, we experimentally identify novel and unique mutational signature imprinted by through the effects its reactive metabolite...
Inactivation of the retinoblastoma tumor suppressor (pRB) alters expression a myriad genes. To understand altered cellular environment that these changes create, we took advantage Drosophila model system and used targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile metabolic occur when RBF1, fly ortholog pRB, is removed. We show RBF1-depleted tissues larvae are sensitive fasting. Depletion RBF1 causes major in nucleotide synthesis glutathione metabolism. Under...
Tobacco usage is linked to multiple cancer types and accounts for a quarter of all cancer-related deaths. smoke contains various carcinogenic compounds, including polycyclic aromatic hydrocarbons (PAH), though the mutagenic potential many tobacco-related chemicals remains largely unexplored. In particular, highly tobacco-specific nitrosamines NNN NNK form pre-mutagenic pyridyloxobutyl (POB) DNA adducts. study presented here, we identified genome-scale POB-induced mutational signatures in...
The retinoblastoma (RB) family of proteins regulate transcription. These lack intrinsic DNA-binding activity but are recruited to specific genomic locations through interactions with sequence-specific factors. best-known target RB protein (pRB) is the E2F transcription factor; however, many other chromatin-associated have been described that may allow members act at additional sites. To gain a perspective on scale E2F-dependent and E2F-independent functions, we generated genome-wide binding...
The 10 key characteristics (KCs) of carcinogens form the basis a framework to identify, organize, and evaluate mechanistic evidence relevant carcinogenic hazard identification. KCs are related mechanisms by which cause cancer. International Agency for Research on Cancer (IARC) Monographs programme has successfully applied evaluation different types exposures, including chemicals, metals, complex such as environmental, occupational, or dietary exposures. use this significantly enhanced...
Chronic exposure to arsenic can lead various health issues, including cancer. Concerns have been mounting about the enhancement of toxicity through co-exposure prevalent lifestyle habits. Smokeless tobacco (SLT) products are commonly consumed in South Asian countries, where their use frequently co-occurs with from contaminated groundwater. To decipher vitro molecular and cellular responses and/or smokeless tobacco, we performed temporal multi-omics analysis transcriptome DNA methylome...
APC/Cdh1 is a major cell cycle regulator and its function has been implicated in DNA damage repair; however, exact role remains unclear. Using affinity purification coupled with mass spectrometry, we identified Claspin as novel Cdh1-interacting protein further demonstrated that Cdh1 ubiquitin substrate. As result, inactivation of leads to activation the Claspin/Chk1 pathway. Previously, Rb interacts influence ability degrade Skp2. Here, report reciprocally regulates pathway through competing...
Many proteins have been proposed to be involved in retinoblastoma protein (pRB)-mediated repression, but it is largely uncertain which cofactors are essential for pRB repress endogenous E2F-regulated promoters.Here we taken advantage of the stream-lined Drosophila dE2F/RBF pathway, has only two E2Fs (dE2F1 and dE2F2), family members (RBF1 RBF2).With RNA interference (RNAi), depleted potential corepressors looked elevated expression groups E2F target genes that known directly regulated by...
dREAM complexes represent the predominant form of E2F/RBF repressor in Drosophila.dREAM associates with thousands sites fly genome but its mechanism action is unknown.To understand genomic context which acts we examined distribution and localization Drosophila E2F proteins.Here report a striking unexpected overlap between dE2F2/dREAM binding for insulator-binding proteins CP190 Beaf-32.Genetic assays show that these components functionally co-operate chromatin immunoprecipitation experiments...
Systematic evaluation of literature data on the cancer hazards human exposures is an essential process underlying prevention strategies. The scope and volume evidence for suspected carcinogens can range from very few to thousands publications, requiring a complex, systematically planned, critical procedure nominate, prioritize evaluate carcinogenic agents. To aid in this process, database fusion, cheminformatics text mining techniques be combined into integrated approach inform agent...
Smarca5, an ATPase of the ISWI class chromatin remodelers, is a key regulator structure, cell cycle and DNA repair. Smarca5 deregulated in leukemia breast, lung gastric cancers. However, its role oncogenesis not well understood. Chromatin remodelers often play dosage-dependent roles cancer. We therefore investigated epigenomic phenotypic impact controlled stepwise attenuation function context primary transformation, process relevant to tumor formation. Upon conditional single- or...
Retinoblastoma tumor suppressor protein (pRb) regulates various biological processes during development and tumorigenesis. Although the molecular mechanism by which pRb controls cell cycle progression is well characterized, how promotes cell-type specification differentiation less understood. Here, we report that Extra Macrochaetae (EMC), Drosophila homolog of inhibitor DNA binding/differentiation (ID), an important contributing to developmental defects caused Rb deficiency. An emc allele...
Abstract The E2F transcription factors are important regulators of the cell cycle whose function is commonly misregulated in cancer. To identify novel E2F1 activity vivo, we used Drosophila to conduct genetic screens. For this, generated transgenic lines that allow tissue-specific depletion dE2F1 by RNAi. Expression these transgenes using Gal4 drivers eyes and wings reliable modifiable phenotypes. We then conducted screens testing capacity Exelixis deficiencies modify E2F1-RNAi From screens,...
The information on candidate cancer driver alterations available from public databases is often descriptive and of limited mechanistic insight, which poses difficulties for reliable distinction between true passenger events. To address this challenge, we performed in-depth analysis whole-exome sequencing data cell lines generated by a barrier bypass-clonal expansion (BBCE) protocol. employed strategy based carcinogen-driven immortalization primary mouse embryonic fibroblasts recapitulates...