A5083775379- Cancer-related gene regulation
- RNA modifications and cancer
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Kruppel-like factors research
- Chronic Myeloid Leukemia Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Advanced biosensing and bioanalysis techniques
- Cancer therapeutics and mechanisms
- Eosinophilic Disorders and Syndromes
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- Glutathione Transferases and Polymorphisms
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- Genomics, phytochemicals, and oxidative stress
- Virus-based gene therapy research
- Renal and related cancers
Helmholtz Zentrum München
2019-2023
Center for Environmental Health
2019-2022
Universitätsklinikum Erlangen
2015-2017
Cancer cells are hallmarked by high proliferation and imbalanced redox consumption signaling. Various oncogenic pathways such as evading cell death converge on redox-dependent signaling processes. Nrf2 is a key regulator in these events operates cytoprotection, drug metabolism malignant progression cancer cells. Here, we show that patients with primary brain tumors (glioblastomas, WHO °IV gliomas, GBM) have devastating outcome overall reduced survival when levels upregulated. overexpression...
The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity vivo. A comprehensive analysis the rRNA landscape 94 patients with acute myeloid (AML) revealed dynamic specifically at exterior sites ribosomes. pattern is closely associated AML stage LSC gene expression signature. Forced 2'-O-methyltransferase...
Acute leukemias represent deadly malignancies that require better treatment. As a challenge, treatment is counteracted by microenvironment protecting dormant leukemia stem cells.To identify responsible surface proteins, we performed deep proteome profiling on minute numbers of patient-derived xenograft (PDX) cells isolated from mice. Candidates were functionally screened establishing comprehensive CRISPR‒Cas9 pipeline in PDX models vivo.A disintegrin and metalloproteinase domain-containing...
Abstract Resistance towards cancer treatment represents a major clinical obstacle, preventing cure of patients. To gain mechanistic insights, we developed model for acquired resistance to chemotherapy by treating mice carrying patient derived xenografts (PDX) acute lymphoblastic leukemia with widely-used cytotoxic drugs 18 consecutive weeks. In two distinct PDX samples, tumors initially responded treatment, until stable disease and eventually tumor re-growth evolved under therapy, at highly...
Clinically relevant methods are not available that prioritize and validate potential therapeutic targets for individual tumors, from the vast amount of tumor descriptive expression data. We established inducible transgene in clinically patient-derived xenograft (PDX) models vivo to fill this gap. With technique at hand, we analyzed role transcription factor Krüppel-like 4 (KLF4) B-cell acute lymphoblastic leukemia (B-ALL) PDX different disease stages. In competitive preclinical trials, found...
<div>Abstract<p>The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, functional evidence that dynamics in ribosomal RNA (rRNA) 2′-O-methylation regulate leukemia stem cell (LSC) activity <i>in vivo</i>. A comprehensive analysis the rRNA landscape 94 patients with acute myeloid (AML) revealed dynamic specifically at exterior sites ribosomes. The pattern is closely associated AML stage LSC gene...
Die Fusion zweier identischer oder unterschiedlicher Zelltypen ist ein Phänomen, welches zum einen physiologisch während der Plazentaentwicklung bei Bildung des Synzytiotrophoblasten auftritt und anderen Kennzeichen zahlreicher maligner Transformationen ist. von Tumor- Normalzelle kann eine Neuinduktion Apoptose- Transdifferenzierungs-Kaskade bewirken so die Tumorigenität reduzieren verstärken. Krebszellen untereinander trägt häufig zu einer Steigerung Malignität mit vaskulären...
<div>Abstract<p>The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, functional evidence that dynamics in ribosomal RNA (rRNA) 2′-O-methylation regulate leukemia stem cell (LSC) activity <i>in vivo</i>. A comprehensive analysis the rRNA landscape 94 patients with acute myeloid (AML) revealed dynamic specifically at exterior sites ribosomes. The pattern is closely associated AML stage LSC gene...
<p>Supplementary Figure S1 shows enrichment of FBL in LSC, correlation with LSC signature and rRNA 2'-O-Me healthy hematopoietic cells. Supplementary S2 the association 2’-O-Me differentiation signatures. S3 strategy for sorting distribution methylation sites on ribosomes. S4 effect knockdown 2’-O-methylation vitro proliferation leukemia S5 show overexpression vivo engraftment primary AML S6 nascent proteome metabolism S7 ribosome footprinting analysis after knockdown. S8 Gm1447...
<p>Supplementary Figure S1 shows enrichment of FBL in LSC, correlation with LSC signature and rRNA 2'-O-Me healthy hematopoietic cells. Supplementary S2 the association 2’-O-Me differentiation signatures. S3 strategy for sorting distribution methylation sites on ribosomes. S4 effect knockdown 2’-O-methylation vitro proliferation leukemia S5 show overexpression vivo engraftment primary AML S6 nascent proteome metabolism S7 ribosome footprinting analysis after knockdown. S8 Gm1447...
Clinic-close methods are not available that prioritize and validate potential therapeutic targets in individual tumors from the vast bulk of descriptive expression data. We developed a novel technique to express transgenes established patient-derived xenograft (PDX) models vivo fill this gap. With at hand, we analyzed role transcription factor Krüppel-like 4 (KLF4) B-cell acute lymphoblastic leukemia (B-ALL) PDX different disease stages. In competitive pre-clinical trials, found...
Background: Tumor-microenvironment interactions are critically important determinants contributing to leukemia formation and maintenance. Interrupting the leukemia-bone marrow interaction represents an attractive therapeutic approach in acute (AL). Functional genomics significantly increases our understanding of vulnerabilities gene dependencies individual tumors. Aims: Here, we developed a CRISPR-Cas9 screening for functional analysis surface molecules patient-derived xenograft (PDX) AL...
Background: Acquired resistance to conventional polychemotherapy regimens leads relapse and poor prognosis, remains a major unmet clinical need. Aims: To identify therapeutic options overcome acquired chemo-resistance. Methods: We studied acute lymphoblastic leukemia (ALL) as model disease combined long-term in vivo treatment orthotopic patient-derived xenograft (PDX) models with multi-omics profiling functional genomic CRISPR/Cas9 screens. Results: adapted chemotherapeutic protocols allow...
Interrupting tumor-microenvironment interactions is an attractive therapeutic strategy. We developed a CRISPR-Cas9 screening approach for functional analysis of surface molecules in patient-derived xenograft (PDX) acute leukemia (AL) models vivo order to decipher tumor specific vulnerabilities. A customized library was run 2 AL PDX samples and candidates were confirmed using competitive approach. ADAM10 depleted both validated 6 models. Treating cells with inhibitor reduced the bone marrow...
Better treatment options are intensively needed for acute leukemias. Before application in clinical trials, novel therapies require preclinical testing which is resource intensive. We established a patient derived xenograft (PDX) mouse model of ALL and AML, allow serial transplantation immunodeficient NSG mice. Up to 5 or AML PDX samples were labelled with an individual genetic barcode fluorochrome, then multiplexed aliquots injected into groups mice (n=4-6). Cells reisolated from murine...