A5078225292- Acute Myeloid Leukemia Research
- Autophagy in Disease and Therapy
- Protein Degradation and Inhibitors
- Glaucoma and retinal disorders
- Histone Deacetylase Inhibitors Research
- Glioma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Calcium signaling and nucleotide metabolism
- Renal cell carcinoma treatment
- Retinoids in leukemia and cellular processes
- Hematological disorders and diagnostics
- Ubiquitin and proteasome pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Liver Disease and Transplantation
- Mycobacterium research and diagnosis
- Travel-related health issues
- Lymphoma Diagnosis and Treatment
- Advanced Biosensing Techniques and Applications
- Bone and Joint Diseases
- Cancer, Hypoxia, and Metabolism
- Polyomavirus and related diseases
- Advanced Proteomics Techniques and Applications
- Mitochondrial Function and Pathology
Goethe University Frankfurt
2018-2025
Frankfurt Cancer Institute
2019-2025
Deutschen Konsortium für Translationale Krebsforschung
2019-2025
Institute of Clinical Cancer Research
2025
University Hospital Frankfurt
2021-2023
German Cancer Research Center
2019-2023
Heidelberg University
2019-2023
University of Regensburg
2014-2019
German Cancer Society
2019
To identify stem cells in the chamber angle of monkey eye by detection 5-bromo-2'-deoxyuridine (BrdU) long-term retention.Four cynomolgus monkeys were treated with BrdU via subcutaneous pumps for 4 weeks. The eyes two animals processed immediately thereafter (group 1) while other animals, treatment was discontinued weeks to allow identification retention 2). number BrdU-positive nuclei quantified, and characterized immunohistochemistry transmission electron microscopy (TEM).The higher at...
Abstract Autophagy is essential for cellular homeostasis and when deregulated this survival mechanism has been associated with disease development. Inhibition of autophagy initiation by inhibiting the kinase ULK1 (Unc-51-like activating 1) proposed as a potential cancer therapy. While inhibitors crystal structures have reported, little known about other closely related ULK2 2). Here, we present structure in complex ATP competitive inhibitors. Surprisingly, revealed dimeric assembly...
Abstract Internal tandem duplications (ITD) in the receptor tyrosine kinase FLT3 occur 25 % of acute myeloid leukemia (AML) patients, drive progression and confer a poor prognosis. Primary resistance to inhibitors (FLT3i) quizartinib, crenolanib gilteritinib is frequent clinical challenge occurs absence identifiable genetic causes. This suggests that adaptive cellular mechanisms mediate primary on-target FLT3i therapy. Here, we systematically investigated responses therapy with multiple...
Introduction CAR-T cell therapy, though successful in hematologic malignancies, faces challenges solid tumors due to limitations of autologous T cells. Cytokine-induced killer (CIK) cells can be given safely across allogeneic barriers and constitute alternative effector generated from healthy donors. CIK are a heterogenous population predominantly with mixed natural (NK) phenotype combine non-MHC-restricted cytotoxicity potent anti-tumor capacity the adaptive immune system. Here, we...
The selective autophagic degradation of mitochondria via mitophagy is essential for preserving mitochondrial homeostasis and, thereby, disease maintenance and progression in acute myeloid leukemia (AML). Mitophagy orchestrated by a variety receptors whose interplay not well understood. Here, we established pairwise multiplexed CRISPR screen targeting to elucidate redundancies gain deeper understanding the functional interactome governing AML. We identified OPTN (optineurin) as sole...
Abstract Background While colorectal cancer (CRC) patients with localized disease have a favorable prognosis, the five-year-survival rate in distant spread is still below 15%. Hence, detailed understanding of mechanisms regulating metastasis formation essential to develop therapeutic strategies targeting metastasized CRC. The notch pathway has been shown be involved metastatic various tumor entities; however, impact its target gene HEYL remains unclear so far. Methods In this study, we...
Abstract High metabolic flexibility is pivotal for the persistence and therapy resistance of acute myeloid leukemia (AML). In 20–30% AML patients, activating mutations FLT3, specifically FLT3-ITD, are key therapeutic targets. Here, we investigated influence FLT3-ITD on metabolism. Nuclear Magnetic Resonance (NMR) profiling showed enhanced reshuffling pyruvate towards tricarboxylic acid (TCA) cycle, suggesting an increased activity dehydrogenase complex (PDC). Consistently, FLT3-ITD-positive...
The optimal follow-up care for relapse detection in acute myeloid leukemia (AML) patients first remission after consolidation therapy with intensive chemotherapy is not established. In this retrospective study, we evaluate the diagnostic value of an surveillance strategy by regular bone marrow aspirations (BMA) these patients. We identified 86 newly diagnosed non-promyelocytic AML who had reached complete (CR) induction and between 2007 2019. Annual rates were 40%, 17%, 2% years 1-3,...
Objectives Multidrug-resistant organisms (MDRO) are considered an emerging threat worldwide. Data covering the clinical impact of MDRO colonization in patients with solid malignancies, however, is widely missing. We sought to determine who have been diagnosed Non-small cell lung cancer (NSCLC) at known high-risk for invasive infections. Materials and methods Patients were screened within a 90-day period after NSCLC diagnosis all stages included this single-center retrospective study. Results...
Intracranial hemorrhage (ICH) in acute myeloid leukemia (AML) patients is a major concern due to the increased risk of mortality. Few studies have examined ICH specifically newly diagnosed AML receiving intensive induction chemotherapy (IC) and prophylactic platelet transfusions during thrombocytopenia <10/nL. This retrospective cohort study included 423 without promyelocytic who underwent IC between 2007 2019. We assessed factors, clinical features, outcomes ICH.17 (4%) suffered hospital...
Autophagy is an important survival mechanism that allows recycling of nutrients and removal damaged organelles has been shown to contribute the proliferation acute myeloid leukemia (AML) cells. However, little known about by which autophagy- dependent AML cells can overcome dysfunctional autophagy. In our study we identified autophagy related protein 3 (ATG3) as a crucial gene for cell conducting CRISPR/Cas9 dropout screen with library targeting around 200 autophagy-related genes....
We performed a retrospective single-center analysis to investigate the diagnostic yield of bone marrow puncture in patients with liver cirrhosis and cytopenia. Liver receiving aspiration or biopsy for work-up otherwise unexplained peripheral blood cytopenia at our institution between 2004 2020 were enrolled this study. evaluated findings from cytologic, histologic immunologic assessment final outcomes. A total 118 median age 55 years Child-Pugh score B (8 points) enrolled. The main...
The nucleolar scaffold protein NPM1 is a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. mutations, known as NPM1c variants promoting its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark AML cells their dependency on elevated autophagic flux. Here, we show that induce autophagy-lysosome pathway by activating master transcription factor TFEB, thereby coordinating expression...
Multiple myeloma (MM) is a malignant plasma cell disorder in which the MYC oncogene frequently dysregulated. Due to its central role, has been proposed as drug target; however, development of clinically applicable molecule modulating activity remains an unmet challenge. Consequently, alternative therapeutic options targeting proteins located downstream MYC. Therefore, we aimed identify undescribed MYC-target MM cells using Stable Isotope Labeling with Amino Acids Cell Culture (SILAC) and...
Abstract Testing for genetic alterations in tumor tissue allows clinicians to identify patients who most likely will benefit from molecular targeted treatment. EXLIQUID – exploiting liquid biopsies advance cancer precision medicine investigates the potential of additional non-invasive tools guiding therapy decisions and monitoring advanced patients. The term “liquid biopsy” (LB) refers analysis tumor-derived circulating material such as cell-free DNA blood samples Although recent...
The mechanistic target of the rapamycin (mTOR) inhibitor, temsirolimus, has significantly improved outcome patients with renal cell carcinoma (RCC). However, development temsirolimus-resistance limits its effect and metastatic progression subsequently recurs. Since integrin α7 (ITGA7) is speculated to promote metastasis, this investigation was designed investigate whether associated altered ITGA7 expression in RCC lines modified tumor adhesion invasion. Caki-1, KTCTL-26, A498 were driven by...
Venous thromboembolic (VTE) events are emerging as frequent complications in acute myeloid leukemia (AML); however, there is insufficient data regarding epidemiology, risk factors, and impact on outcomes. The optimal approach to balance risks of thrombosis hemorrhage remains unclear. This retrospective single-center study AML patients undergoing induction chemotherapy between 2007 2018 assessed incidence, features, outcomes early-onset VTE.423 (median age 59 years) were enrolled. VTE was...
Abstract Treatment‐related complications contribute substantially to morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. Although AML are susceptible fluid overload (FO) (e.g., the context of chemotherapy protocols, during sepsis treatment or prevent tumor lysis syndrome), little attention has been paid its role receiving between 2014 2019 were included this study. FO was defined as ≥5% weight gain on day 7 compared baseline determined...