A5018094804- Protein Degradation and Inhibitors
- Nuclear Receptors and Signaling
- Histone Deacetylase Inhibitors Research
- Chronic Lymphocytic Leukemia Research
- Cancer-related gene regulation
- Sarcoma Diagnosis and Treatment
- RNA modifications and cancer
- Lymphoma Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Immunotherapy and Immune Responses
- Bone Metabolism and Diseases
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Bone health and treatments
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Diverse Approaches in Healthcare and Education Studies
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Education, Safety, and Science Studies
- Renal and related cancers
- Immunodeficiency and Autoimmune Disorders
- Autophagy in Disease and Therapy
- Bone health and osteoporosis research
- RNA Research and Splicing
Heidelberg University
2015-2025
German Cancer Research Center
2015-2025
National Center for Tumor Diseases
2015-2024
Korea Institute of Oriental Medicine
2013-2014
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships mutations to phenotypes remain largely unknown. Here, we measured ex vivo sensitivity 246 blood cancers 63 drugs alongside genome, transcriptome, DNA methylome analysis understand determinants drug response. We assembled a primary cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer....
✓ The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time craniotomy label cells deoxyribonucleic acid (DNA) synthesis; percentage S-phase cells, or BUdR labeling index (LI), each tumor determined immunohistochemically. In 29 patients (60%), tumors had LI's less than 1%, indicating a slow growth rate; only three (10%) these died recurrent during follow-up period...
Abstract Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in variants that are oncogenic sensitive inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a...
Abstract Impaired homologous recombination (HR) repair of DNA double-strand breaks (DSB) renders cancer cells sensitive to poly(ADP-ribose) polymerase inhibitors (PARPi). This synthetic lethal relationship is used treat several epithelial cancers. However, the efficacy PARPi often limited by primary or acquired resistance, which might be overcome rational combination therapies. We previously observed that most patients with advanced chordoma, a spinal neoplasm no standard treatments, show...
The stem of Acer tegmentosum has been widely used in Korea for the treatment hepatic disorders. In this study, we investigated bone protective effect water extract (WEAT). We found that WEAT inhibits osteoclast differentiation induced by receptor activator nuclear factor-κB ligand (RANKL), an essential cytokine differentiation. precursor cells, inhibited RANKL-induced activation JNK, NF-κB, and cAMP response element-binding protein, leading to suppression induction c-Fos factor activated T...
The rhizome of Atractylodes macrocephala has been used mainly in Traditional Chinese Medicine for invigorating the functions stomach and spleen. In present study, we investigated inhibitory effect 70% ethanol extract (AMEE) on osteoclast differentiation. We found that AMEE inhibits differentiation from its precursors induced by receptor activator nuclear factor-κB ligand (RANKL), an essential cytokine required attenuated RANKL-induced activation NF-κB signaling pathway, subsequently...
Burkitt lymphoma (BL) is a highly aggressive B-cell associated with MYC translocation. Here, we describe drug response profiling of 42 blood cancer cell lines including 17 BL to 32 drugs targeting key pathways and provide systematic study combinations in lines. Based on response, identified line specific sensitivities, i.e. venetoclax driven by BCL2 overexpression partitioned subsets kinase inhibitors. In the combination screen, BET, BTK PI3K inhibitors, synergistic inhibition Akt, mTOR, BET...
Burkitt lymphoma cells (BL) exploit antigen-independent tonic signals transduced by the B cell antigen receptor (BCR) for their survival, but molecular details of rewired BLspecific BCR signal network remain unclear. A loss function screen revealed SH2 domain-containing 5`-inositol phosphatase 2 (SHIP2) as a potential modulator BL fitness. We characterized role SHIP2 in survival several models and show that perturbing renders more susceptible to apoptosis, while attenuating proliferation...
Abstract The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. Since has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS. Here we demonstrate that enhanced pathway activity represents a hallmark FUS::DDIT3-expressing lines well tissue...
Abstract Purpose: The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. As has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS. Experimental Design: Immunohistochemical evaluation was performed a large cohort specimens. dependency and...
<div>AbstractPurpose:<p>The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. As has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS.</p>Experimental Design:<p>Immunohistochemical evaluation was performed a...
<p>Supplementary Figure S5. Causal relationship between FUS::DDIT3-modulated G1/S cell cycle checkpoint regulation and requirement for WEE1 activity.</p>
<p>Supplementary Figure S1. WEE 1 expression correlates with histological grade of MLS.</p>
<p>Supplementary Figure S3. Supplementary In vivo efficacy of WEE 1 inhibition in MLS CAM xenografts.</p>
<p>Supplementary Figure S6. CDK 2 expression exacerbates replication stress in MLS.</p>