A5002830698- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Hearing, Cochlea, Tinnitus, Genetics
- Protein Degradation and Inhibitors
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Single-cell and spatial transcriptomics
- Chromatin Remodeling and Cancer
- interferon and immune responses
- RNA modifications and cancer
- Extracellular vesicles in disease
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Cancer Cells and Metastasis
- Hearing Loss and Rehabilitation
- Neuroblastoma Research and Treatments
- Ubiquitin and proteasome pathways
- Circular RNAs in diseases
- Hippo pathway signaling and YAP/TAZ
- Mass Spectrometry Techniques and Applications
Heidelberg University
2018-2024
National Center for Tumor Diseases
2018-2024
University Hospital Heidelberg
2018-2024
German Cancer Research Center
2020-2023
DKFZ-ZMBH Alliance
2023
Brain (Germany)
2020
Memorial Sloan Kettering Cancer Center
2011-2017
Institut de génétique et de développement de Rennes
2013
Kettering University
2011
Tufts University
2007-2010
The recent discovery of mutations in metabolic enzymes has rekindled interest harnessing the altered metabolism cancer cells for therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1), which mutated multiple human cancers. Here, we examine role mutant IDH1 fully transformed with endogenous mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen blocked, dose-dependent manner, ability enzyme (mIDH1) to produce R-2-hydroxyglutarate...
Breast cancer methylomes contribute to metastatic potential, modulate the metastasis transcriptome, and predict disease outcome.
// Sevin Turcan 1,* , Armida W. M. Fabius Alexandra Borodovsky 2 Alicia Pedraza 1 Cameron Brennan Jason Huse Agnes Viale 3 Gregory J. Riggins and Timothy A. Chan 1,4,5 Human Oncology Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Department of Neurosurgery, School Medicine, Johns Hopkins University, Baltimore, MD. Genomics Core, 4 Dept. Radiation Oncology, 5 Brain Tumor * These authors contributed equally to this work Correspondence: Chan, email: Keywords :...
Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent low grade and progressive gliomas characterized by the production of 2-hydroxyglutarate (2-HG) from α-ketoglutarate mutant enzyme. 2-HG is an "oncometabolite" that competitively inhibits α-KG dependent dioxygenases resulting various widespread cellular changes including abnormal hypermethylation genomic DNA suppression differentiation. Despite growing understanding IDH gliomas, development effective therapies has proved...
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, complex regulatory presiding over initiation and maintenance tumors still poorly understood. There is untapped value in identifying therapeutic targets broadly govern coordinated modules dictating progression. Here, we reverse engineered interrogated a breast cancer-specific interaction network...
Mutations in isocitrate dehydrogenase (IDH) genes occur multiple cancer types, lead to global changes the epigenome, and drive tumorigenesis. Yet, effective strategies targeting solid tumors harboring IDH mutations remain elusive. Here, we demonstrate that IDH-mutant gliomas cholangiocarcinomas display elevated DNA damage. Using vitro preclinical animal models of glioma cholangiocarcinoma, developed treatment use a synthetic lethality approach reduced damage repair conferred by mutant using...
Although homomeric channels assembled from the alpha9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both alpha10 subunits. To gain insight into vivo, we examined olivo cochlear innervation null-mutant mice. Electrophysiological recordings postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents...
Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, small number patients live much longer than the median survival. A better understanding these long-term survivors (LTSs) may provide important insight into biology GBM. We identified 7 GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), survival >48 months. characterized transcriptome each patient and determined rates MGMT promoter methylation IDH1 IDH2 mutational status. LTSs in 2 independent...
The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition astrocyte-like, oligodendrocyte progenitor-like, cycling tumor subpopulations, a population enriched for ribosomal genes translation elongation factors primarily...
Abstract: The emergence of epigenetic mechanisms as key regulators gene expression has led to dramatic advances in understanding cancer biology. Driven by complex layers that include aberrant DNA methylation and histone modification, aberrations have emerged critical processes disrupt cellular machinery homeostasis. Recent discoveries already translated into successful clinical trials improved patient care, with several agents approved for hematologic disease others undergoing study. As the...
Capicua (CIC) is an important downstream molecule of RTK/RAS/MAPK pathway. The regulatory mechanism CIC underlying tumorigenesis in oligodendroglioma, where frequently mutated, has yet to be fully elucidated. Using patient-derived glioma lines, RNA-sequencing and bioinformatic analysis publicly available databases, we investigated how loss- or gain-of-function regulates its targets, cell proliferation glutamate release. Our results indicate increased frequency truncating mutations...
The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear chromatin structure. basis these incompletely understood. DNA methylome primary cancers contribute to transcriptomic heterogeneity different metastatic behavior. Therefore we sought characterize remodeling during regional metastasis. We profiled the 44 matched tumors metastases. Striking subtype-specific patterns metastasis-associated were observed, which reflected...
Decitabine (DAC) is an FDA-approved DNA methyltransferase (DNMT) inhibitor that used in the treatment of patients with myelodysplastic syndromes. Previously, we showed DAC marks antitumor activity against gliomas isocitrate dehydrogenase 1 (IDH1) mutations. Based on promising preclinical results, a clinical trial has been launched to determine effect IDH-mutant gliomas. The next step comprehensively assess efficacy and potential determinants response malignant gliomas.The expression...