A5070621356- Neuroblastoma Research and Treatments
- Developmental Biology and Gene Regulation
- Cancer, Hypoxia, and Metabolism
- Marine Biology and Ecology Research
- Ion channel regulation and function
- Planarian Biology and Electrostimulation
- Invertebrate Immune Response Mechanisms
- Signaling Pathways in Disease
- Cancer therapeutics and mechanisms
- Neurobiology and Insect Physiology Research
- Nerve injury and regeneration
- Linguistics and language evolution
- Hippo pathway signaling and YAP/TAZ
- Translation Studies and Practices
- Neurogenesis and neuroplasticity mechanisms
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- Protist diversity and phylogeny
- Lung Cancer Research Studies
- Echinoderm biology and ecology
- Marine Ecology and Invasive Species
- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
- Neonatal Respiratory Health Research
- FOXO transcription factor regulation
University of Gothenburg
2015-2022
University of Regensburg
2014
Justus-Liebig-Universität Gießen
2012-2014
Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg Palmer, 2013). Vertebrate ALK considered to be an orphan receptor the identity ligand(s) is critical issue. Here we show that FAM150A FAM150B are potent ligands for bind extracellular domain addition wild-type able drive 'superactivation' activated mutants from neuroblastoma. In conclusion, our data robustly by FAM150A/B provide...
Significance Neuroblastoma is a pediatric tumor arising from the neural crest. Dysregulation of receptor tyrosine kinase ALK has been linked to neuroblastoma, making it important understand its function in native conditions. In zebrafish, related receptor—Ltk—is also expressed crest and regulates development specific pigment cells—iridophores. Ligands activating human were recently identified as ALKAL proteins (FAM150, AUG) by biochemical means. Our data show that this ligand–receptor pair...
Anaplastic lymphoma kinase (ALK) is a tyrosine receptor which has been implicated in numerous solid and hematologic cancers. ALK mutations are reported about 5-7% of neuroblastoma cases but the ALK-positive percentage increases significantly relapsed patient population. Crizotinib, first clinically approved inhibitor for treatment lung cancer had less dramatic responses neuroblastoma. Here we investigate efficacy second-generation inhibitor, brigatinib, setting. Employing cell lines, mouse...
In this study, we aimed to identify molecular mechanisms involved in the specification of 4d (mesentoblast) lineage Platynereis dumerilii. We employ RT-PCR and situ hybridization against dumerilii twist homolog (Pdu-twist) reveal mesodermal within lineage. show that Pdu-twist mRNA is already maternally distributed. After fertilization, ooplasmatic segregation leads relocation transcripts into somatoblast (2d) 4d, indicating maternal component might be an important prerequisite for further...
The Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) plays a critical role in the specification of founder cells (FCs) Drosophila visceral mesoderm (VM) during embryogenesis. Reporter gene and CRISPR/Cas9 deletion analysis reveals enhancer regions upstream Alk locus that influence tissue-specific expression amnioserosa (AS), VM epidermis. By performing high throughput yeast one-hybrid screens (Y1H) with library transcription factors (TFs) we identify Odd-paired (Opa),...
Basement membranes (BMs) are specialized layers of extracellular matrix (ECM) mainly composed Laminin, type IV Collagen, Perlecan and Nidogen/entactin (NDG). Recent in vivo studies challenged the initially proposed role NDG as major ECM linker molecule by revealing dispensability for viability BM formation. Here, we report characterization single Ndg gene Drosophila. Embryonic expression was primarily observed mesodermal tissues chordotonal organs, whereas protein localized to all BMs. While...
After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity generate new neurons and glia from an endogenous pool of progenitor cells compensate neural cell loss following certain lesions. The aim present study was investigate whether replacement (neurogenesis or gliogenesis) in brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC;...
Although activating mutations of the anaplastic lymphoma kinase (ALK) membrane receptor occur in ∼10% neuroblastoma (NB) tumors, role wild-type (WT) receptor, which is aberrantly expressed most non-mutated cases, unclear. Both WT and mutant proteins undergo extracellular domain (ECD) cleavage. Here, we map cleavage site to Asn654-Leu655 demonstrate that inhibition ALK significantly impedes NB cell migration with subsequent prolongation survival mouse models. Cleavage results downregulation...
Alk signaling in the developing Drosophila visceral mesoderm requires scaffolding protein Cnk and its binding partner Ave.
ABSTRACT Activating anaplastic lymphoma kinase (ALK) receptor tyrosine (RTK) mutations occur in pediatric neuroblastoma and are associated with poor prognosis. To study ALK-activating a genetically controllable system, we employed CRIPSR/Cas9, incorporating orthologs of the human oncogenic ALKF1174L ALKY1278S Drosophila Alk locus. AlkF1251L AlkY1355S mutant exhibited enhanced signaling phenotypes, but unexpectedly depended on Jelly belly (Jeb) ligand for activation. Both larval brains...
Abstract Anaplastic lymphoma kinase (Alk) is a receptor tyrosine of the insulin super-family that functions as oncogenic driver in range human cancers such neuroblastoma. In order to investigate mechanisms underlying Alk signaling, we conducted genetic suppressor screen Drosophila melanogaster . Our identified multiple loci important for including members Ras/Raf/ERK-, Pi3K-, and STAT-pathways well tailless (tll) foxo whose orthologues NR2E1/TLX FOXO3 are transcription factors implicated...
ABSTRACT In Drosophila , the receptor tyrosine kinase Alk and its ligand Jeb are required to drive founder cell (FC) specification in visceral mesoderm (VM). Alk-signalling activates downstream MAPK/ERK- PI3K-pathways human but little is known about immediate signalling events. Here we report that scaffolding protein Cnk interacts directly with via a novel c-terminal binding motif. for as ectopic expression of minimal interaction motif well loss maternal zygotic cnk blocks FC-formation,...
Abstract Mutations in Anaplastic Lymphoma Kinase (ALK) are implicated somatic and familial neuroblastoma, a paediatric tumour of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK the related Leukocyte Tyrosine (LTK). In zebrafish Danio rerio , DrLtk, which is similar to sequence domain structure, controls development iridophores, pigment cells. Hence, system allows studying Alk/Ltk...
Abstract Over the last decade Anaplastic Lymphoma Kinase (ALK), a receptor tyrosine kinase (RTK), has been identified as fusion partner in diverse variety of translocation events resulting oncogenic signaling many different cancer types. In tumors where full-length ALK RTK itself is mutated, such neuroblastoma, picture regarding role an driver less clear. Neuroblastoma complex and heterogeneous tumor that arises from neural crest-derived peripheral nervous system. Although high-risk...
Abstract Activating Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase (RTK) mutations occur in pediatric neuroblastoma and are associated with poor prognosis. To study ALK-activating a genetically controllable system we employed CRIPSR/Cas9, incorporating orthologues of the human oncogenic ALK F1174L Y1278S Drosophila Alk locus. F1251L Y1355S mutant exhibit enhanced signaling phenotypes, but unexpectedly depend on Jelly belly (Jeb) ligand for activation. Both larval brains display...