A5007214937- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Protease and Inhibitor Mechanisms
- Sarcoma Diagnosis and Treatment
- Apelin-related biomedical research
- Microtubule and mitosis dynamics
- Chemical Synthesis and Analysis
- Epigenetics and DNA Methylation
- Blood Coagulation and Thrombosis Mechanisms
- Click Chemistry and Applications
- Acute Lymphoblastic Leukemia research
- Reproductive Biology and Fertility
- 14-3-3 protein interactions
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- RNA Interference and Gene Delivery
German Cancer Research Center
2022-2025
Heidelberg University
2022-2025
Hopp Children's Cancer Center Heidelberg
2022-2023
Epigenomics (Germany)
2023
Constructor University
2019-2021
Universitätsmedizin Göttingen
2020
Max Planck Institute for Biophysical Chemistry
2019
Mammalian oocytes segregate chromosomes with a microtubule spindle that lacks centrosomes, but the mechanisms by which acentrosomal spindles are organized and function largely unclear. In this study, we identify conserved subcellular structure in mammalian forms phase separation. This structure, term liquid-like meiotic domain (LISD), permeates poles dynamic protrusions extend well beyond spindle. The LISD selectively concentrates multiple regulatory factors allows them to diffuse rapidly...
T-cell acute lymphocytic leukemia protein 1 (TAL1) is one of the most frequently deregulated oncogenes in lymphoblastic (T-ALL). Its deregulation can occur through diverse cis-alterations, including SIL-TAL1 microdeletions, translocations with Receptor loci, and more recently described upstream intergenic non-coding mutations. These mutations consist recurrent focal microinsertions that create an oncogenic neo-enhancer accompanied by activating epigenetic marks. This observation laid...
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...
Abstract The SS18-SSX fusion drives oncogenic transformation in synovial sarcoma by bridging SS18, a member of the mSWI/SNF (BAF) complex, to Polycomb repressive complex 1 (PRC1) target genes. Here we show that ability occupy H2AK119ub1-rich regions is an intrinsic property its SSX C terminus, which can be exploited transcriptional regulators beyond SS18. Accordingly, recruitment occurs manner independent core components and catalytic activity BAF. Alternative fusions are also recruited...
Kallikrein 13 (KLK13) was first identified as an enzyme that is downregulated in a subset of breast tumors. This serine protease has since been implicated number pathological processes including ovarian, lung and gastric cancers. Here we report the design, synthesis deconvolution libraries internally quenched fluorogenic peptide substrates to determine specificity substrate binding subsites KLK13 prime non-prime regions (according Schechter Berger convention). The with consensus sequential...
Abstract The HER2-positive breast cancer subtype (HER2 + -BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2 -BC. However, large number become refractory to current targeted therapies, necessitating development new treatment strategies. Epigenetic regulators are commonly misregulated in and represent attractive molecular therapeutic targets. Monoubiquitination histone 2B (H2Bub1) by heterodimeric ubiquitin...
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...
Increased plasma and adipose tissue protease activity is observed in patients with type 2 diabetes obesity. It has been proposed that specific proteases contribute to the link between obesity, inflammation metabolic diseases. We have recently shown ablation of serine kallikrein-related peptidase 7 (Klk7) specifically preserves systemic insulin sensitivity protects mice from obesity-related AT inflammation. Here, we investigated whether whole body Klk7 knockout (Klk7−/−) develop a phenotype...
Kallikrein-related peptidases (KLKs) and matrix metalloproteinases (MMPs) are secretory proteinases known to proteolytically process components of the extracellular matrix, modulating pericellular environment in physiology pathologies. The interconnection between these families remains elusive. To assess cross-activation families, we developed a peptide, fusion protein-based exposition system (Cleavage exposed amino acid sequences, CleavEx) aiming at investigating potential KLK14 recognize...
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...
Abstract The HER2-driven breast cancer subtype displays a particularly aggressive behavior. Alterations of the epigenome are common in cancers and represent attractive novel molecular therapeutic targets. Monoubiquitination histone 2B (H2Bub1) by its obligate heterodimeric E3 ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions loss H2Bub1 associated with progression. In this study, we utilized human samples, cell culture models, mammary carcinoma mouse...
ABSTRACT Kallikrein-related peptidases (KLKs) and matrix metalloproteinases (MMPs) are secretory proteinases known to proteolytically process components of the extracellular (ECM), thus modulating pericellular environment in physiology excessively pathologies like cancer. However, interconnection between these groups proteases remains elusive. To test this hypothesis, we have developed a peptide library-based exposition system ( Cleav age ex posed amino acid sequences, CleavEx) aiming at...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
ABSTRACT The SS18-SSX fusion drives oncogenic transformation in synovial sarcoma by bridging SS18, a member of mSWI/SNF complex, to Polycomb repressive complex 1 (PRC1) target genes. Here we show that the SSX C-terminus, via its SSXRD domain, directs chromatin binding independently SS18. specific targeting is mediated interaction with mono ubiquitinated H2A (H2AK119ub1) and histone MacroH2A which overlaps genome wide. Variant Repressive Complex 1.1 (PRC1.1) acts as main depositor H2AK119ub1...