A5020409208- Glioma Diagnosis and Treatment
- Ocular Oncology and Treatments
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Advanced biosensing and bioanalysis techniques
- Vascular Malformations Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
- Inflammatory Bowel Disease
- PI3K/AKT/mTOR signaling in cancer
- RNA Interference and Gene Delivery
- Microscopic Colitis
- Virus-based gene therapy research
- Protist diversity and phylogeny
- Cancer-related molecular mechanisms research
- Mathematical Biology Tumor Growth
- Chromatin Remodeling and Cancer
- Intraperitoneal and Appendiceal Malignancies
- Cancer Cells and Metastasis
- interferon and immune responses
- Ferroelectric and Negative Capacitance Devices
- Genomic variations and chromosomal abnormalities
German Cancer Research Center
2012-2021
Heidelberg University
2012-2021
Deutschen Konsortium für Translationale Krebsforschung
2016-2021
Hopp Children's Cancer Center Heidelberg
2021
AbbVie (Germany)
2016-2018
Abstract In vivo functional investigation of oncogenes using somatic gene transfer has been successfully exploited to validate their role in tumorigenesis. For tumour suppressor genes this proven more challenging due technical aspects. To provide a flexible and effective method for investigating loss-of-function alterations influence on tumorigenesis, we have established CRISPR/Cas9-mediated disruption, allowing targeting TSGs. Here demonstrate the utility approach by deleting single ( Ptch1...
Mutations in chromatin modifier genes are frequently associated with neurodevelopmental diseases. We herein demonstrate that the chromodomain helicase DNA-binding protein 7 (Chd7), CHARGE syndrome, is indispensable for normal cerebellar development. Genetic inactivation of Chd7 granule neuron progenitors leads to hypoplasia mice, due impairment differentiation, induction apoptosis and abnormal localization Purkinje cells, which closely recapitulates known clinical features cerebella...
Abstract Purpose: Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in remains unknown. Experimental Design: patient-derived cell culture model, DKFZ-BT66, was used demonstrate presence SASP and analyze impact...
Pilocytic astrocytoma (PA) is the most common type of primary brain tumor in children and second frequent cancer childhood. Children with incompletely resected PA represent a clinically challenging patient cohort for whom conventional adjuvant therapies are only moderately effective. This has produced high clinical demand testing new molecularly targeted treatments. However, development therapeutics been hampered by lack an adequate vivo model. Recent studies have identified activation MAPK...
Group3 medulloblastoma (MBG3) that predominantly occur in young children are usually associated with MYC amplification and/or overexpression, frequent metastasis and a dismal prognosis. Physiologically relevant MBG3 models currently lacking, making inferences related to their cellular origin thus far limited. Using utero electroporation, we here report mouse can be developed situ from different multipotent embryonic cerebellar progenitor cells via conditional expression of Myc loss Trp53...
Pilocytic astrocytoma (PA) is the most frequent pediatric brain tumor. Activation of MAPK pathway well established as oncogenic driver disease. It frequently caused by KIAA1549:BRAF fusions, and leads to oncogene induced senescence (OIS). OIS thought be a major reason for growth arrest PA cells in vitro vivo, preventing establishment cultures. Hence, valid preclinical models are currently very limited, but testing new compounds urgently needed. We transduced short-term culture DKFZ-BT66...
One key advantage of the CRISPR/Cas9 system in comparison with other gene editing approaches lies its potential for multiplexing. Here, we describe an elaborate procedure that allows assembly multiple gRNA expression cassettes into a vector choice within single step, termed ASAP(Adaptable System Assembly multiplexed Plasmids)-cloning. We demonstrate utility ASAP-cloning CRISPR-mediated applications, including efficient multiplex editing, robust transcription activation and convenient...
Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive pediatric brain tumors that characterized by a recurrent mutation (K27M) within the histone H3 encoding genes H3F3A and HIST1H3A/B/C. These mutations have been shown to induce global reduction in repressive modification H3K27me3, which together with widespread changes DNA methylation patterns results an extensive transcriptional reprogramming hampering identification of single therapeutic targets based on molecular rationale.We...
Successful RNAi applications depend on strategies allowing robust and persistent expression of minimal gene silencing triggers without perturbing endogenous expression. Here, we propose a novel avenue which is integration promoterless shmiRNA, i.e. shRNA embedded in micro-RNA (miRNA) scaffold, into an engineered genomic miRNA locus. For proof-of-concept, used TALE or CRISPR/Cas9 nucleases to site-specifically integrate anti-hepatitis C virus (HCV) shmiRNA the liver-specific miR-122/hcr locus...
Research Article4 July 2018Open Access Source DataTransparent process Cited4 is a sex-biased mediator of the antidiabetic glitazone response in adipocyte progenitors Irem Bayindir-Buchhalter orcid.org/0000-0003-2532-109X DKFZ Junior Group Metabolism and Stem Cell Plasticity, German Cancer Center, Heidelberg, Germany Search for more papers by this author Gretchen Wolff Sarah Lerch Tjeerd Sijmonsma orcid.org/0000-0001-8950-2987 Division Chronic Inflammation Cancer, Center (DKFZ), Maximilian...
Adult pilocytic astrocytomas (PAs) have been regarded as indistinguishable from pediatric PAs in terms of genome-wide expression and methylation patterns. It has unclear whether adult arise early life remain asymptomatic until adulthood, or they develop during adulthood. We sought to determine the age origin human using two types "marks" genomic DNA. First, we analyzed DNA patterns distinguish between different anatomic locations (n = 257 PA control brain tissues). Second, measured...
Medulloblastoma (MB) is one of the most common malignant brain tumors in children. The current treatment regimen consists tumor resection and subsequent chemo- radiotherapy. Long-term morbidity due to this aggressive a major problem MB therapy.
Abstract Modeling cancer in mice through engineering of candidate genes the germline has long been gold standard for validation putative oncogenes or tumor suppressor (TSGs). For TSGs, whereby loss-of-function (LOF) mutations act as a driver malignant transformation, this traditionally accomplished using constitutive cell type-specific knockout strategies mediated by homologous recombination embryonic stem cells. While allows evaluation susceptibility to generation genetically engineered...
Abstract Two key properties of glioblastomas are vascular proliferation and invasion tumor cells into the surrounding tissues, both limiting efficacy surgery radiochemotherapy treatment regimens. Inhibition mammalian target rapamycin (mTOR) by Temsirolimus (CCI-779) only has modest single compound activity in recurrent glioma. Given fact that postoperative is standard care first-line newly diagnosed glioblastoma, first part presented project aims at analyzing combined mTOR/radiotherapy...
Transabdominal ultrasound (US) is a non-invasive diagnostic modality providing objective parameters of Crohn’s disease (CD) activity. Disease management concepts (treat-to-target, T2T, tight control) integrate and clinical for guiding treatment optimisation resulting in improved outcomes as demonstrated by the CALM study adalimumab (Ada) therapy. Hence, US such bowel wall thickening (BWT) could serve adjunctive optimisation. Here, we assessed utility monitoring response to Ada This...
Pilocytic astrocytoma (PA), the most frequent pediatric brain tumor, exhibits an activation of MAPK-signaling by genetic aberration in nearly 100% cases, with activating KIAA1549:BRAF-fusions being alteration this pathway (60 – 80%). Dealing a single-pathway disease evokes hope for improvement PA treatment small molecule inhibitors MAPK-signalling pathway. However, faithful preclinical models are currently very limited. The paradoxical acceleration tumor growth patients treated sorafenib,...