A5035899357- Acute Myeloid Leukemia Research
- Genetic factors in colorectal cancer
- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Chronic Lymphocytic Leukemia Research
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Acute Lymphoblastic Leukemia research
- Genomics and Chromatin Dynamics
- Chronic Myeloid Leukemia Treatments
- Heparin-Induced Thrombocytopenia and Thrombosis
- Cancer Genomics and Diagnostics
- Platelet Disorders and Treatments
- SARS-CoV-2 and COVID-19 Research
- Glycosylation and Glycoproteins Research
- Retinal and Optic Conditions
- CAR-T cell therapy research
- RNA modifications and cancer
- Retinoids in leukemia and cellular processes
- Cancer, Hypoxia, and Metabolism
- Erythrocyte Function and Pathophysiology
Goethe University Frankfurt
2012-2023
Helmholtz-Institute Ulm
2021
Stable gene expression in mammalian cells is a prerequisite for many vitro and vivo experiments. However, either the integration of plasmids into genomes or use retro-/lentiviral systems have intrinsic limitations. The transposable elements, e.g. Sleeping Beauty system (SB), circumvents most these drawbacks (integration sites, size limitations) allows quick generation stable cell lines. process SB catalyzed by transposase handling this transfer easy, fast safe. Here, we report our...
Abstract During the last months many countries have started immunization of millions people by using vector-based vaccines. Unfortunately, severe side effects became overt during these vaccination campaigns: cerebral venous sinus thromboses (CVST), absolutely rare under normal life conditions, were found as a effect that occured 4-14 days after first vaccinations. Besides CVST, Splanchnic Vein Thrombosis (SVT) was also observed. This type adverse event has not been observed in clinical...
To fight the COVID-19 pandemic caused by RNA virus SARS-CoV-2, a global vaccination campaign is in progress to achieve immunization of billions people mainly with adenoviral vector- or mRNA-based vaccines, all which encode SARS-CoV-2 Spike protein. In some rare cases, cerebral venous sinus thromboses (CVST) have been reported as severe side effect occurring 4-14 days after first and were often accompanied thrombocytopenia. Besides CVST, splanchnic vein (SVT) other thromboembolic events...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of disease COVID-19, which has become a global concern due to its rapid spread. common methods monitor and quantitate SARS-CoV-2 infectivity in cell culture are so far time-consuming labor-intensive. Using Sleeping Beauty transposase system, we generated robust versatile cellular infection model that allows experiments compatible for high-throughput live imaging. based on lung derived A549 cells, show...
Phenotypical screening is a widely used approach in drug discovery for the identification of small molecules with cellular activities. However, functional annotation identified hits often poses challenge. The development narrow or exclusive target selectivity such as chemical probes and chemogenomic (CG) libraries, greatly diminishes this challenge, but non-specific effects caused by compound toxicity interference basic functions still pose problem to associate phenotypic readouts molecular...
Our focus is the identification, characterisation and functional analysis of different MLL fusions. In general, fusion proteins are encoded by large cDNA cassettes that difficult to transduce into haematopoietic stem cells. This due size limitations packaging process those vector-encoded RNAs retro- or lentiviral particles. Here, we present our efforts in establishing a universal vector system analyse The cloning was embedded backbone Sleeping Beauty transposable element. transposon has no...
MLL gene aberrations are frequently diagnosed in infant acute myeloid leukemia (AML). We previously described the MLL-NEBL and NEBL-MLL genomic fusions an AML patient with a chromosomal translocation t(10;11)(p12;q23). NEBL was second Nebulin family member (LASP1, NEBL) which found to be involved rearrangements. Here, we report on our attempts unravel oncogenic properties of both fusion genes. First, RT-PCR analyses revealed presence mRNAs diagnostic sample patient. Next, expression...
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 Genomic DNA is the optimal resource to analyze questions concerning genetic changes that are related oncogenesis. This article tries summarize recent efforts chromosomal trigger development of human acute myeloid and lymphoblastic leukemias. The aim this study was establish an universal method enables identification characterization translocations MLL gene at genomic nucleotide level. Chromosomal result illegitimate recombination events in hematopoietic stem or precursor cells,...
We among others have recently demonstrated that normal cells produce "fusion mRNAs". These fusion mRNAs do not derive from rearranged genomic loci, but rather they are derived "early-terminated transcripts" (ETTs). Premature transcriptional termination takes place in intronic sequences belong to "breakpoint cluster regions". One important property of ETTs is exhibit an unsaturated splice donor site. This results in: (1) splicing "cryptic exons" present the final intron; (2) Splicing another...
Chromosomal translocations (CTs) are a genetic hallmark of cancer. They could be identified as recurrent aberrations in hemato-malignancies and solid tumors. More than 40% all "cancer genes" were CTs. Most these CTs result the production oncofusion proteins which many have been studied over past decades. influence signaling pathways and/or alter gene expression. However, precise mechanism for how arise occur nearly identical fashion individuals remains to elucidated. Here, we performed...
Abstract Leukemia patients bearing t(6;11)(q27;q23) translocations can be divided in two subgroups: those with breakpoints the major breakpoint cluster region of MLL (introns 9–10; associated mainly AML M1/4/5), and others minor 21–23), T-ALL. We cloned all four resulting fusion genes ( MLL-AF6 , AF6-MLL exMLL-AF6 AF6-shMLL ) subsequently transfected them to generate stable cell culture models. Their molecular function was tested by inducing gene expression for 48 h a Doxycycline-dependent...
Phenotypical screening is a widely used approach in drug discovery for the identification of small molecules with cellular activities. However, functional annotation identified hits often poses challenge. The development narrow or exclusive target selectivity such as chemical probes and chemogenomic (CG) libraries, greatly diminishes this challenge, but non-specific effects caused by compound toxicity interference basic functions still problem to associate phenotypic readouts molecular...
Recent pathomolecular studies on the MLL-AF4 fusion protein revealed that murinized version of MLL-AF4, MLL-Af4 protein, was able to induce leukemia when expressed in murine or human hematopoietic stem/progenitor cells (Lin et al. Cancer Cell 30:737-749, 2016). In parallel, a group from Japan demonstrated pSer domain AF4 as well is bind Pol I transcription factor complex SL1 (Okuda Nat Commun 6:8869, 2015). Here, we investigated and pSer-murinized thereof for their functional properties...
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