A5072877122- PI3K/AKT/mTOR signaling in cancer
- Fibroblast Growth Factor Research
- Developmental Biology and Gene Regulation
- Protein Degradation and Inhibitors
- Neurogenesis and neuroplasticity mechanisms
- Zebrafish Biomedical Research Applications
- Enzyme Structure and Function
- Heat shock proteins research
- Biochemical and Molecular Research
- Sarcoma Diagnosis and Treatment
- Congenital heart defects research
- Peptidase Inhibition and Analysis
- Rangeland and Wildlife Management
- Retinoids in leukemia and cellular processes
- Ecology and Vegetation Dynamics Studies
- Pancreatic and Hepatic Oncology Research
- Pancreatitis Pathology and Treatment
- Histiocytic Disorders and Treatments
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Fire effects on ecosystems
- thermodynamics and calorimetric analyses
- Soft tissue tumor case studies
Institute of Cancer Research
2021-2024
Cancer Research UK
2022-2023
Portland State University
2015
Monoaminergic neurons include the physiologically important central serotonergic and noradrenergic subtypes. Here, we identify zinc-finger transcription factor, Insm1, as a crucial mediator of differentiation both subtypes, in particular acquisition their neurotransmitter phenotype. Insm1 is expressed hindbrain progenitors monoaminergic they exit cell cycle, pattern that partially overlaps with expression proneural factor Ascl1. Consistent this, conserved cis-regulatory sequence associated...
Cell diversity and organization in the neural tube depend on integration of extrinsic signals acting along orthogonal axes. These are believed to specify distinct cellular identities by triggering all-or-none changes expression combinations transcription factors [1Jessell T.M. Neuronal specification spinal cord: inductive transcriptional codes.Nat. Rev. Genet. 2000; 1: 20-29Crossref PubMed Scopus (1638) Google Scholar]. Under influence a common dorsoventral signal, sonic hedgehog,...
This paper focuses on the 2013 Carpenter One Fire in Spring Mountains National Recreation Area (SMNRA) to understand how linked social and ecological factors affect fire regimes ecosystems that exist close proximity human settlement places culturally significant Indigenous peoples. Ignited July, this ultimately spread 11,283 ha cost USD $18.5 million contain extinguish. Priority was placed protecting various private landholdings within Forest its periphery, which included several seasonal,...
Rhabdomyosarcomas are aggressive pediatric soft‐tissue sarcomas and include high‐risk PAX3–FOXO1 fusion‐gene‐positive cases. Fibroblast growth factor receptor 4 (FGFR4) is known to contribute rhabdomyosarcoma progression; here, we sought investigate the involvement potential for therapeutic targeting of other FGFRs in this disease. Cell‐based screening FGFR inhibitors with clinical repurposing (NVP‐BGJ398, nintedanib, dovitinib, ponatinib) revealed greater sensitivity versus...
The molecular chaperone heat shock protein 90 (HSP90) works in concert with co-chaperones to stabilize its client proteins, which include multiple drivers of oncogenesis and malignant progression. Pharmacologic inhibitors HSP90 have been observed exert a wide range effects on the proteome, including depletion induction dissociation from HSP90, disruption signaling networks, recruitment ubiquitylation degradation machinery—suggesting widespread remodeling cellular complexes. However,...
Abstract Eukaryotic initiation factor 4E (eIF4E) serves as a regulatory hub for oncogene-driven protein synthesis and is considered promising anticancer target. Here we screen fragment library against eIF4E identify ligand-binding site with previously unknown function. Follow-up structure-based design yields low nM tool compound ( 4 , K d = 0.09 µM; LE 0.38), which disrupts the eIF4E:eIF4G interaction, inhibits translation in cell lysates, demonstrates target engagement intact cells (EC 50 2...
Abstract The translation initiation factor eIF4E is a rate-limiting for protein synthesis that binds the mRNA m7G-cap to initiate recruitment and binding of eIF4F components such as eIF4G. Targeting has long been considered promising anticancer strategy but it remained undruggable using conventional screening approaches. Fragment-based crystallographic powerful technique probing surface proteins identify potentially druggable sites. Here, we describe fragment-based combination Xray...
(Current Biology 23, 412–418; March 4, 2013) As a result of an author oversight at the proof stage, Ryoichiro Kageyama’s first name was initially misspelled as “Ryoichoro” in this article online and print. This error has now been corrected online. The authors apologize for any confusion that may have resulted. Retinoid Acid Specifies Neuronal Identity through Graded Expression Ascl1Jacob et al.Current BiologyFebruary 14, 2013In BriefCell diversity organization neural tube depend on...
The molecular chaperone heat shock protein 90 (HSP90) works in concert with co-chaperones to stabilize its client proteins, which include multiple drivers of oncogenesis and malignant progression. Pharmacologic inhibitors HSP90 have been observed exert a wide range effects on the proteome, including depletion induction dissociation from HSP90, disruption signaling networks, recruitment ubiquitylation degradation machinery—suggesting widespread remodeling cellular complexes. However,...
Abstract Initiation of translation is considered the main rate-limiting step protein synthesis and requires recognition 5’ m7G-cap on mature mRNAs formation eukaryotic initiation factor 4F (eIF4F) multi-protein mRNA cap-binding complex. Formation this complex interaction eIF4E scaffold eIF4G, RNA helicase eIF4A. This eIF4F along with eIF3 mediate recruitment 40S ribosomal particle to 5′ cap mRNA. Activation a regulatory hub many major oncogenic pathways, thus, targeting has emerged as...
Abstract The translation initiation factor eIF4E binds the mRNA m7G-cap to initiate recruitment and binding of eIF4F components such as eIF4G. exhibits oncogenic activity in vitro vivo assays high expression cancers is associated with poor prognosis resistance chemotherapeutics targeted agents. Targeting has long been considered a promising anticancer strategy but this target remained undruggable using conventional screening approaches. In an accompanying submission we describe...