A5084265463- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Endoplasmic Reticulum Stress and Disease
- Vitamin C and Antioxidants Research
- Lymphoma Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Monoclonal and Polyclonal Antibodies Research
- Genetics and Neurodevelopmental Disorders
- Autophagy in Disease and Therapy
- RNA Research and Splicing
- Carcinogens and Genotoxicity Assessment
- Signaling Pathways in Disease
- DNA Repair Mechanisms
- Sirtuins and Resveratrol in Medicine
- PARP inhibition in cancer therapy
- Long-Term Effects of COVID-19
- Tuberous Sclerosis Complex Research
- Inflammation biomarkers and pathways
- Immune responses and vaccinations
- CAR-T cell therapy research
Friedrich Schiller University Jena
2015-2025
Josep Carreras Leukaemia Research Institute
2021
Jena University Hospital
2015
Charité - Universitätsmedizin Berlin
2010-2011
Abstract Cytotoxic stress activates stress-activated kinases, initiates adaptive mechanisms, including the unfolded protein response (UPR) and autophagy, induces programmed cell death. Fatty acid unsaturation, controlled by stearoyl-CoA desaturase (SCD)1, prevents cytotoxic but mechanisms are diffuse. Here, we show that 1,2-dioleoyl- sn -glycero-3-phospho-(1’-myo-inositol) [PI(18:1/18:1)] is a SCD1-derived signaling lipid, which inhibits p38 mitogen-activated kinase activation, counteracts...
Abstract Cell death programs such as apoptosis and ferroptosis are associated with aberrant redox homeostasis linked to lipid metabolism membrane function. Evidence for cross-talk between these is emerging. Here, we show that cytotoxic stress channels polyunsaturated fatty acids via lysophospholipid acyltransferase 12 into phospholipids become susceptible peroxidation under additional stress. This reprogramming altered acyl-CoA synthetase isoenzyme expression caused by a decrease in growth...
Abstract Overexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting the transcription factor remains challenging. Here, we show that inhibition histone deacetylase 6 (HDAC6) using HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic levels prevents lymphomagenesis mouse model -induced aggressive B-cell lymphoma. M-100 specifically alters protein-protein interactions by switching acetylation state substrates, such as tubulin....
Abstract Impaired T lymphopoiesis is associated with immunosuppression of the adaptive immune response and plays a role in morbidity mortality patients animal models sepsis. Although previous studies examined several intrathymic mechanisms that negatively affect lymphopoiesis, extrathymic remain poorly understood. Here, we report dramatic decrease percentage early lineage progenitors (ETPs) three sepsis mice (cecal ligation puncture, lipopolysaccharide continuous injection, poly I:C...
The nucleotide analogue azacitidine (AZA) is currently the best treatment option for patients with high-risk myelodysplastic syndromes (MDS). However, only half of treated respond and these almost all eventually relapse. New options are urgently needed to improve clinical management patients. Here, we perform a loss-of-function shRNA screen identify histone acetyl transferase transcriptional co-activator, CREB binding protein (CBP), as major regulator AZA sensitivity. Compounds inhibiting...
Abstract Acute lymphoblastic leukemia (ALL) is an aggressive blood cancer that mainly affects children. Relapse rates are high and toxic chemotherapies block DNA replication induce damage lead to health problems later in life, underlining the need for improved therapies. MYC a transcription factor hyperactive large proportion of cancers including but difficult target therapy. We show ablation function BTB/POZ domain Zbtb17 (Miz-1), important cofactor c-Myc, significantly delayed T-...
Article20 September 2018Open Access Transparent process Tuberous sclerosis complex is required for tumor maintenance in MYC-driven Burkitt's lymphoma Götz Hartleben European Research Institute the Biology of Ageing, University Medical Centre Groningen, The Netherlands Leibniz Age Research, Fritz Lipmann Institute, Jena, Germany Search more papers by this author Christine Müller Andreas Krämer Heiko Schimmel Pathology, Jena Hospital, Laura M Zidek Carsten Dornblut René Winkler Center...
We provide a descriptive characterization of the unfolded protein response (UPR) in skeletal muscle human patients with peritoneal sepsis and model C57BL/6J mice. Patients undergoing open surgery were included cross-sectional study blood samples taken. Key markers UPR cluster differentiation 68 (CD68) as surrogate inflammatory injury evaluated by real-time PCR histochemical staining. CD68 mRNA increased animals (p < 0.05). Mainly inositol-requiring enzyme 1α branch was upregulated shown...
In a wide range of lymphoid neoplasms, the process malignant transformation is associated to somatic mutations in B cells that affect epigenetic machinery. Consequential alterations histone modifications contribute disease-specific changes transcriptional program. Affected genes commonly play important roles cell cycle regulation, apoptosis-inducing signal transduction and DNA damage response, thus facilitating emergence traits impair immune surveillance favor different B-cell lymphoma...
Sepsis is a life-threatening condition caused by dysregulated host responses to infection. Myeloid cell accumulation and lymphocyte decline are widely recognized phenomena in septic patients. However, the fate of specific immune cells remains unclear. Here, we report results human explorative study patients with peritonitis undergoing abdominal surgery without sepsis. We analyzed pairwise peritoneal fluid peripheral blood taken 24 h after characterize immediate changes. Our show that myeloid...
A major transcriptional output of cells is ribosomal RNA (rRNA), synthesized by polymerase I (Pol I) from multicopy rRNA genes (rDNA). Constitutive silencing an rDNA fraction promoter CpG methylation contributes to the stabilization these otherwise highly active loci. In cancers driven oncoprotein Myc, excessive Myc directly stimulates transcription. However, it not clear when during carcinogenesis this mechanism emerges, and how Myc-driven activation affects epigenetic silencing. Here, we...
Abstract Overexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting the transcription factor remains challenging. Here, we show that inhibition histone deacetylase 6 (HDAC6) using HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic levels prevents lymphomagenesis mouse model -induced aggressive B-cell lymphoma. M-100 specifically alters protein-protein interactions by switching acetylation state substrates, such as tubulin....
Abstract Objective: The Myc-interacting zinc finger protein 1 (Miz-1) is a ubiquitous BTB/POZ domain and that acts as both transcriptional repressor activator. POZ of Miz-1 enables protein-protein interactions facilitates stable association with chromatin. binds to the proto-oncogen c-Myc modulates target gene expression. Overexpression an important feature Burkitt-type B cell lymphomas (BL) caused by rearrangements. aim this project determine if crucial collaborator in regulation cells...
In vitro the histone deacetylase 6 (HDAC6) has been shown to be a major of heat shock protein 90 (HSP90). It is mediating glucocorticoid receptor (GR) ligand interaction since correct folding GR as HSP90 client depends on acetylation status. We could recently show that HDAC6 deficiency results in an attenuation dex-induced whole-body glucose intolerance well insulin resistance. present study we investigated underlying mechanism modulator metabolic function.
<div>Abstract<p>Acute lymphoblastic leukemia (ALL) is an aggressive blood cancer that mainly affects children. Relapse rates are high and toxic chemotherapies block DNA replication induce damage lead to health problems later in life, underlining the need for improved therapies. MYC a transcription factor hyperactive large proportion of cancers including but difficult target therapy. We show ablation function BTB/POZ domain Zbtb17 (Miz-1), important cofactor c-Myc, significantly...
<p>Supplementary Figures + Supplementary Materials and Methods</p>