A5035535768- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Plant biochemistry and biosynthesis
- Advanced Proteomics Techniques and Applications
- PI3K/AKT/mTOR signaling in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Animal Virus Infections Studies
- Developmental Biology and Gene Regulation
- Heme Oxygenase-1 and Carbon Monoxide
- Cerebrovascular and genetic disorders
- Protein Degradation and Inhibitors
- Fuel Cells and Related Materials
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Viral-associated cancers and disorders
- MicroRNA in disease regulation
- Phytochemical compounds biological activities
- Peptidase Inhibition and Analysis
- 14-3-3 protein interactions
Sylvester Comprehensive Cancer Center
2015-2023
University of Miami
2015-2022
Menlo School
2022
Hexagon (United States)
2022
Mount Sinai Hospital
2001
Lunenfeld-Tanenbaum Research Institute
2001
University of Toronto
2001
Notch proteins function as receptors for membrane-bound ligands (Jagged and Delta-like) to regulate cell-fate determination. We have investigated the role of signaling in embryonic endothelium mouse by expressing an activated form Notch4 protein vasculature under regulation Flk1 (VEGFR) locus. Expression results a growth developmental delay lethality at about 10 days postcoitum. The extent developing mutant embryos was restricted, fewer small vessels were seen, vascular networks...
Amyloid bodies (A-bodies) are inducible membrane-less nuclear compartments composed of heterogeneous proteins that adopt an amyloid-like state. A-bodies seeded by noncoding RNA derived from stimuli-specific loci the rDNA intergenic spacer (rIGSRNA). This raises question how rIGSRNA recruits a large population diverse to confer A-body identity. Here, we show long low-complexity dinucleotide repeats operate as architectural determinants rIGSRNA. On stimulus, clusters with simple...
Abstract Protein expression evolves under greater evolutionary constraint than mRNA levels, and translation efficiency represents a primary determinant of protein levels during stimuli adaptation. This raises the question as to translatome remodelers that titrate output from populations. Here, we uncover network RNA-binding proteins (RBPs) enhances glycolytic in cells responding oxygen deprivation. A system-wide proteomic survey translational engagement identifies family oxygen-regulated...
Highlights•MATRIX produces system-wide blueprints of active translation factors•eIF5B is an essential component the hypoxic protein synthesis machinery•eIF5B surrogate eIF2 that facilitates met-tRNAiMet delivery•Central carbon metabolism proteins are principally reliant on eIF5B for translationSummaryThe eukaryotic initiation factor 5B (eIF5B) a homolog IF2, ancient enables initiator methionine-tRNAiMet (met-tRNAiMet) loading prokaryotic ribosomes. While it can be traced back to last...
Heme oxygenases (HOs) -1 and -2 catalyze the breakdown of heme to release carbon monoxide, biliverdin, ferrous iron, which may preserve cell function during oxidative stress. HO-1 levels decrease in endothelial cells exposed hypoxia, whereas effect hypoxia on HO-2 expression is unknown. The current study was carried out determine if alters protein human whether this enzyme plays a role preserving their viability hypoxic Human umbilical vein (HUVECs), aortic (HAECs), blood outgrowth were 21%...
Tactical disruption of protein synthesis is an attractive therapeutic strategy, with the first-in-class eIF4A-targeting compound zotatifin in clinical evaluation for cancer and COVID-19. The full cellular impact mechanisms these potent molecules are undefined at a proteomic level. Here, we report mass spectrometry analysis translational reprogramming by rocaglates, cap-dependent initiation disruptors that include zotatifin. We find effects to be far more complex than simple "translational...
Abstract Translatome reprogramming is a primary determinant of protein levels during stimuli adaptation. This raises the question: what are translatome remodelers that reprogram output to activate biochemical adaptations. Here, we identify translational pathway represses metabolism safeguard genome integrity. A system-wide MATRIX survey identified ancient eIF5A as pH-regulated translation factor responds fermentation-induced acidosis. TMT-pulse-SILAC analysis several pH-dependent proteins,...
Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery central its oncogenicity. By upregulating hypoxia-inducible factors (HIFs), KSHV reprograms infected cells a hypoxia-like state, triggering angiogenesis. Here we identify link between replicative biology and oncogenicity by showing that KSHV's regulate HIF2α levels localization endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through...
Here, we present a protocol using MATRIX (mass spectrometry analysis of active translation factors ribosome density fractionation and isotopic labeling experiments) platform to investigate changes the protein synthesis machinery in U87MG glioblastoma cells response rocaglate silvestrol. This describes steps perform SILAC (stable isotope by amino acids cell culture), fractionation, isolation, mass analysis. approach can be applied study any adaptive remodeling machineries. For complete...
Abstract Background: 40% of diffuse large B-cell lymphoma (DLBCL) patients do not achieve cure in response to the standard immunochemotherapy. Relapsed and refractory tumors respond poorly targeted signaling inhibitors due pathway redundancies this genetically heterogenous disease. Pharmacologic disruption cap-initiation complex eIF4F is an emerging clinical treatment strategy bypass resistance. In preclinical experiments, B-lymphomas show high susceptibility rocaglates, natural synthetic...
Abstract Introduction: Eukaryotic translation initiation factor 2α (eIF2α) is a core component of the cellular machinery. Alterations in eIF2α phosphorylation constitute key adaptation during variety physiological stresses, including oxygen deprivation (hypoxia). We recently found that cancer cells respond to hypoxia through systemic reprogramming cap-dependent mRNA efficiencies by switching hypoxic eIF4F, eIF4FH. In present study, we sought elucidate role(s) and dephosphorylation this...
Abstract Intro: Deregulated protein synthesis is a common trait across solid and hematologic malignancies an attractive target for cancer therapy. Rocaglates compounds that inhibit eukaryotic initiation factor 4A1 (eIF4A1), the essential DEAD-box RNA helicase resolves mRNA 5’UTR secondary structures during cap-dependent translation initiation. Rocaglates’ unique mechanism of action causes sequence-selective binding by eIF4A1, clamping inactive onto transcript. This suppresses globally...