A5090797991- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Chromatin Remodeling and Cancer
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Histone Deacetylase Inhibitors Research
- Genetic Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- interferon and immune responses
Heidelberg University
2023-2024
German Cancer Research Center
2023-2024
Epigenomics (Germany)
2023-2024
Koç University
2021-2022
AT-rich interaction domain protein 1A (ARID1A), a SWI/SNF chromatin remodeling complex subunit, is frequently mutated across various cancer entities. Loss of ARID1A leads to DNA repair defects. Here, we show that plays epigenetic roles promote both double-strand breaks (DSBs) pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). accumulated at DSBs after damage regulates loops formation by recruiting RAD21 CTCF DSBs. Simultaneously, facilitates transcription...
Acute myeloid leukemia with complex karyotype (ckAML) is characterized by high genomic complexity, including frequent TP53 mutations and chromothripsis. Genomic rearrangements that reposition active enhancers near proto-oncogenes, leading to their aberrant expression, have not been systematically investigated in AML. To facilitate the discovery of such "enhancer hijacking" events, we developed pyjacker, a computational tool, applied it 39 ckAML samples. Pyjacker identified several enhancer...
Epigenetic reprogramming to pluripotency requires extensive remodeling of chromatin landscapes silence existing cell-type-specific genes and activate genes. ATP-dependent complexes are important regulators structure gene expression; however, the role recently identified Bromodomain-containing protein 9 (BRD9) associated non-canonical BRG1-associated factors (ncBAF) complex in remains unknown. Here, we show that genetic or chemical inhibition BRD9, as well ncBAF subunit GLTSCR1, but not...
Acute myeloid leukemia with complex karyotype (ckAML) is characterized by high genomic complexity, including frequent TP53 mutations and chromothripsis. We hypothesized that the numerous rearrangements could reposition active enhancers near proto-oncogenes, leading to their aberrant expression. developed pyjacker, a computational tool for detection of enhancer hijacking events, applied it cohort 39 ckAML samples. Pyjacker identified motor neuron pancreas homeobox 1 (MNX1), gene aberrantly...
Friedreich's ataxia (FRDA, OMIM#229300) is the most common hereditary ataxia, resulting from reduction of frataxin protein levels due to expansion GAA repeats in first intron FXN gene. Why triplet repeat causes a decrease Frataxin not entirely known. Generation effective FRDA disease models crucial for answering questions regarding pathophysiology this disease. There have been considerable efforts generate vitro and vivo FRDA. In perspective article, we highlight studies conducted using...
Abstract Epigenetic dysregulation is a hallmark of Acute Myeloid Leukemia (AML), with mutations in DNA Methyltransferases (e.g., DNMT3A) being frequent and promising therapeutic targets. DNMTs form complexes Histone (HMTs), driving gene silencing loop via chromatin methylation crosstalk. However, potential connections between this DNMTs/HMTs cooperative activity oncogenic requirements across the AML mutational spectrum remain poorly understood. Here, we demonstrate that AMLs carrying DNMT3A...
Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Deletions in the long arm of chromosome 7 (del7q) are recurrent events acute (AML) which associated with an unfavorable outcome. Since search for recessive tumor suppressor genes located within deleted region was unsuccessful, prevalent idea currently is that haploinsufficiency one or more drive this leukemia. Other studies showed structural rearrangements such as translocations and inversions can lead to...
Friedreich's ataxia (FRDA) is a rare neurodegenerative disorder which caused by triplet repeat expansion (GAA) in the first intron of FXN gene. In this present study, we generated induced pluripotent stem cells (iPSC) lines from fibroblasts three unrelated FRDA patients using integration-free episomal vectors. All iPSC express pluripotency markers such as OCT4 and SSEA4, display normal karyotypes can differentiate into all germ layers via vivo teratoma formation assay.
Abstract Epigenetic reprogramming requires extensive remodeling of chromatin landscapes to silence cell-type specific gene expression programs. ATP-dependent chromatin-remodeling complexes are important regulators structure and expression; however, the role Bromodomain-containing protein 9 (BRD9) associated ncBAF (non-canonical BRG1-associated factors) complex in remains unknown. Here, we show that genetic suppression BRD9 as well subunit GLTSCR1, but not closely related BRD7, increase...
Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: (AML) is an aggressive hematological malignancy resulting from a block in the differentiation of progenitors and activation growth promoting genes. In clinics, hypomethylating agents (HMA) such as 5-azacitidine (AZA) or 2-deoxy-5-azacytidine (decitabine) are routinely used to treat patients with AML. Chromosomal rearrangements AML can lead aberrant oncogene by juxtaposition activating enhancer, phenomenon known...