A5041983716- Acute Myeloid Leukemia Research
- Cell Adhesion Molecules Research
- Hematological disorders and diagnostics
- Chronic Myeloid Leukemia Treatments
- Caveolin-1 and cellular processes
- Erythrocyte Function and Pathophysiology
- Retinoids in leukemia and cellular processes
- Immune cells in cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Research on Leishmaniasis Studies
- Eosinophilic Disorders and Syndromes
- S100 Proteins and Annexins
- Cytokine Signaling Pathways and Interactions
- Bone and Joint Diseases
- Trypanosoma species research and implications
- Proteoglycans and glycosaminoglycans research
- Hematopoietic Stem Cell Transplantation
- Immune Response and Inflammation
- Bone health and treatments
- Protease and Inhibitor Mechanisms
- Crustacean biology and ecology
- Lipid metabolism and disorders
- Cellular Mechanics and Interactions
- Insect symbiosis and bacterial influences
- Pancreatitis Pathology and Treatment
Goethe University Frankfurt
2024-2025
Georg Speyer Haus
2017-2024
University of Bern
2024
The endosteal bone marrow niche and vascular endothelial cells provide sanctuaries for leukemic cells. In murine chronic myeloid leukemia (CML) CD44 on E-selectin endothelium are essential mediators the engraftment of stem We hypothesized that non-adhesion CML-initiating to may lead superior eradication in CML after treatment with imatinib than alone. Indeed, here we show inhibitor GMI-1271 combination prolongs survival mice via decreased contact time endothelium. Non-adhesion BCR-ABL1+...
LeishGEM is a genome-wide functional annotation community resource for Leishmania mexicana, where deletion mutant growth in vitro and vivo measured protein localisation determined by endogenous tagging LOPIT-DC (localisation of organelle proteins isotope with differential centrifugation) spatial proteomics. Data are being made available pre-publication via http://leishgem.org which allows data-driven identification the mechanisms parasitism.
Abstract The bone marrow microenvironment is a critical regulator of haematopoietic stem cell self-renewal and fate 1 . Although it appreciated that ageing, chronic inflammation other insults compromise function thereby negatively affect haematopoiesis 2 , not known whether different compartments exhibit distinct microenvironmental properties functional resilience. Here we use imaging, pharmacological approaches mouse genetics to uncover specialized in adult ageing skull. Specifically, show...
Inflammation promotes solid tumor progression, but how regulatory mechanisms of inflammation may affect leukemia is less well studied. Using annexin A5 (ANXA5), a calcium-binding protein known for apoptosis, which we discovered to be differentially expressed in the bone marrow microenvironment (BMM) mice with acute myeloid (AML) vs chronic leukemia, as model system, unravel here circuit AML-derived necrosis factor α (TNF-α) dose-dependently reduces ANXA5 BMM. This creates an inflammatory BMM...
Benzoxazepinones have been extensively studied as exclusively selective RIP kinase 1 inhibitors. This scaffold binds a type-III inhibitor targeting the αC-out/DFG-out conformation. inactive conformation results in large expansion of back pocket, that has also reported for LIM kinases. Scaffold hopping is common design orthosteric inhibitors, but not explored allosteric mainly due to typically exclusive selectivity type III Here, we hypothesized shared structural properties LIMKs and RIPKs...
Abstract Therapy resistance in leukemia may be due to cancer cell-intrinsic and/or -extrinsic mechanisms. Mutations within BCR-ABL1 , the oncogene giving rise chronic myeloid (CML), lead tyrosine kinase inhibitors (TKI), and some are associated with clinically more aggressive disease worse outcome. Using retroviral transduction/transplantation model of CML human cell lines we faithfully recapitulate accelerated course TKI resistance. We show various models, that murine imatinib-resistant...
Abstract Lipid raft-associated proteins play a vital role in membrane-mediated processes. The lipid microdomain-associated protein flotillin 2 (FLOT2), which has scaffolding function, is involved polarization, as well actin cytoskeletal organization of primitive and mature hematopoietic cells been associated with different malignancies. However, its involvement myeloid leukemias not studied. Using murine transplantation models, we show here that the absence FLOT2 from leukemia-initiating...
Abstract Haematopoietic stem cells (HSC) reside in the bone marrow microenvironment (BMM), where they respond to extracellular calcium [eCa 2+ ] via G-protein coupled calcium-sensing receptor (CaSR). Here we show that a gradient exists this BMM, and response differ between leukaemias. CaSR influences location of MLL-AF9 + acute myeloid leukaemia (AML) within niche differentially impacts AML versus BCR-ABL1 Deficiency reduces leukaemic (LSC) 6.5-fold. interacts with filamin A, crosslinker...
Abstract Leukemia cells reciprocally interact with their surrounding bone marrow microenvironment (BMM), rendering it hospitable to leukemia cell survival, for instance through the release of small extracellular vesicles (sEVs). In contrast, we show here that BMM deficiency pleckstrin homology domain family M member 1 (PLEKHM1), which serves as a hub between fusion and secretion intracellular is important vesicular in osteoclasts, accelerates murine BCR-ABL1+ B-cell acute lymphoblastic...
Fibrinolysis influences the mobilization of hematopoietic stem cells from their bone marrow microenvironment (BMM). Here we show that activation plasmin, a key fibrinolytic agent, by annexin A2 (ANXA2) distinctly impacts progression BCR-ABL1+ B-cell acute lymphoblastic leukemia (B-ALL) via modulation extracellular matrix (ECM) in BMM. The dense ECM BMM with decreased plasmin activity entraps insulin-like growth factor (IGF) 1 and reduces mTORC2-dependent signaling proliferation B-ALL cells....
<title>Abstract</title> The bone marrow microenvironment is a critical regulator of hematopoietic stem cell self-renewal and fate. While it appreciated that aging, chronic inflammation other insults compromise function thereby negatively affect hematopoiesis, not known whether different compartments exhibit distinct microenvironmental properties functional resilience. Here, we have employed imaging, pharmacological approaches, mouse genetics to uncover specialized highly surprising in adult...