A5077710470- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Immunodeficiency and Autoimmune Disorders
- Cancer-related gene regulation
- Glycosylation and Glycoproteins Research
- Cancer Genomics and Diagnostics
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Pancreatic and Hepatic Oncology Research
- Acute Myeloid Leukemia Research
- Autonomous Vehicle Technology and Safety
- RNA modifications and cancer
- Synthesis and Catalytic Reactions
- Traffic Prediction and Management Techniques
- Sphingolipid Metabolism and Signaling
- Histone Deacetylase Inhibitors Research
- Autophagy in Disease and Therapy
- Galectins and Cancer Biology
- Computational Drug Discovery Methods
- Immune Cell Function and Interaction
European Molecular Biology Laboratory
2017-2025
Heidelberg University
2022-2025
University Hospital Heidelberg
2022-2025
North China University of Technology
2024
Heinrich Heine University Düsseldorf
2024
Düsseldorf University Hospital
2024
Integrated Oncology (United States)
2024
European Molecular Biology Organization
2018-2023
European Molecular Biology Laboratory
2023
Heidelberg University
2023
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....
Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates protein–protein interaction (PPI) between catalytic subunit EZH2 EED. Deregulated PRC2 is intimately involved in tumorigenesis progression, making it an invaluable target for epigenetic cancer therapy. However, until now, there have been no reported small molecule compounds targeting EZH2-EED interactions. In...
Abstract The autophagic ubiquitin‐like protein LC3 functions through interactions with LC3‐interaction regions (LIRs) of other autophagy proteins, including receptors, which stands out as a promising protein–protein interaction (PPI) target for the intervention autophagy. Post‐translational modifications like acetylation Lys49 on LIR‐interacting surface could disrupt interaction, offering an opportunity to design covalent small molecules interfering interface. Through screening compounds, we...
The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. PTCL had clonal rearrangement, which was already detectable in the apheresis product CAR manufacturing and 7 months earlier autologous transplantation. Somatic
Abstract Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond currently established genomic transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize transcriptome alongside genetic ex-vivo drug profiling a annotated CLL discovery cohort (n = 68). Unsupervised clustering data reveals six...
Histone methyltransferases are involved in various biological functions, and these methylation regulating enzymes' abnormal expression or activity has been noted several human cancers. Within this context, SET domain-containing (lysine methyltransferase) 7 (SET7, also called KMT7, SETD7, SET9) is of increasing significance due to its diverse roles functions diseases, such as diabetes, cancers, alopecia areata, atherosclerotic vascular disease, HIV, HCV. In study, DC-S100, which was...
The ATP-dependent Clp protease (ClpP) plays an essential role not only in the control of protein quality but also regulation bacterial pathogen virulence, making it attractive target for antibacterial treatment. We have previously determined crystal structures Staphylococcus aureus ClpP (SaClpP) two different states, extended and compressed. To investigate dynamic switching between these we performed a series molecular dynamics simulations. During structural transition, long straight helix E...
Abstract The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated remains unknown because this process involves a complex interplay immune microenvironments epithelial cells. To obtain more systematic understanding of as to identify novel therapeutic approaches, we constructed knowledge-based network describing development colitis-associated colon cancer (CAC) by integrating extracellular...
The M2 subtype Acute Myeloid Leukemia (AML-M2) with t(8;21) represents an unmet challenge because of poor clinical outcomes in a sizable portion patients. In this study,we report that FTY720 (Fingolimod), sphingosine analogue and FDA approved drug for treating multiple sclerosis, shows antitumorigenic activity against the Kasumi-1 cell line, xenograft mouse models leukemic blasts isolated from AML-M2 patients translocation. Primary investigation indicated caused apoptosis through caspases...
Abstract While phosphatidylinositol 4-kinase (PI4KIIα) has been identified as a potential target for antitumor therapy, the clinical applications of PI4KIIα are limited by lack specific inhibitors. Here we report first small-molecule inhibitor (SMI) human PI4KIIα. Docking-based and ligand-based virtual screening strategies were employed to identify promising hits, followed two rounds kinase activity inhibition validation....
Abstract Ex vivo drug response profiling is a powerful tool to study genotype–drug associations and being explored as set for precision medicine in cancer. Here we conducted prospective non-interventional trial investigate feasibility of ex treatment guidance hematologic malignancies (SMARTrial, NCT03488641 ). The primary endpoint provide reports within 7 d was met 91% all participants ( N = 80). Secondary analysis revealed that resistance chemotherapeutic drugs predicted chemotherapy...
Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and dysfunction have been identified as essential factors emergence ICB Here, we found that protein arginine methyltransferase 1 (PRMT1) expression was inversely correlated with number activity CD8+ T cells within melanoma specimen. PRMT1 inhibition DCPT1061 significantly restrained refractory growth...
Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, is a flavin-dependent amine oxidase which specifically demethylates mono- or dimethylated H3K4 and H3K9 via redox process. It participates in broad spectrum of biological processes high importance cell proliferation, adipogenesis, spermatogenesis, chromosome segregation embryonic development. To date, as potential drug target for discovering anti-tumor drugs, medical significance LSD1 has been greatly...
The histone acetylation of post-translational modification can be highly dynamic and play a crucial role in regulating cellular proliferation, survival, differentiation motility. Of the enzymes that mediate post-translation modifications, GCN5 acetyltransferase (HAT) proteins family add acetyl groups to target lysine residues within histones, has been most extensively studied. According mechanism studies related proteins, two key processes, deprotonation acetylation, must involved. However,...