2023
An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Zhou W, Li W, Wang S, Salovska B, Hu Z, Tao B, Di Y, Punyamurtula U, Turk B, Sessa W, Liu Y. An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells. Nature Communications 2023, 14: 3803. PMID: 37365174, PMCID: PMC10293293, DOI: 10.1038/s41467-023-39514-1.Peer-Reviewed Original ResearchConceptsPhosphorylation sitesSerine/threonine kinase AktMass spectrometry-based phosphoproteomicsThreonine kinase AktAkt-dependent phosphorylationAberrant Akt activationEndothelial cellsKinase substrateKinase AktCell signalingPhosphorylation profilePhenotypic outcomesDownstream signalingAkt activationAkt1 phosphorylationHuman diseasesSystem-level analysisAKT1Vascular endothelial cellsRich resourcePhosphorylationSignalingGrowth factorAktCellsGenetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
Lee S, Schleer H, Park H, Jang E, Boyer M, Tao B, Gamez-Mendez A, Singh A, Folta-Stogniew E, Zhang X, Qin L, Xiao X, Xu L, Zhang J, Hu X, Pashos E, Tellides G, Shaul P, Lee W, Fernandez-Hernando C, Eichmann A, Sessa W. Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice. Nature Cardiovascular Research 2023, 2: 438-448. PMID: 39196046, PMCID: PMC11358031, DOI: 10.1038/s44161-023-00266-2.Peer-Reviewed Original ResearchLDL transcytosisLDL receptor knockout miceReceptor knockout miceAtherosclerotic cardiovascular diseaseLow-density lipoprotein accumulationHigh-fat dietPromising therapeutic strategyTherapeutic neutralizationMacrophage infiltrationTriglyceride levelsLDL entryCardiovascular diseaseSelective monoclonal antibodiesLipoprotein accumulationTherapeutic strategiesKnockout micePlaque formationAtherosclerosis initiationType 1Genetic deletionArterial wallMonoclonal antibodiesEndothelial cellsLDL accumulationMice
2022
Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes
Rodrigues MA, Gomes DA, Fiorotto R, Guerra MT, Weerachayaphorn J, Bo T, Sessa WC, Strazzabosco M, Nathanson MH. Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes. Hepatology Communications 2022, 6: 2748-2764. PMID: 35852334, PMCID: PMC9512452, DOI: 10.1002/hep4.2042.Peer-Reviewed Original ResearchConceptsLipid raftsCaveolin-1Intact lipid raftsType 3 inositol trisphosphate receptorApical regionC-terminal amino acidsTrisphosphate receptor type 3Madin-Darby canine kidney cellsCanine kidney cellsFluorescence microscopy techniquesInositol trisphosphate receptorApical localizationTrisphosphate receptorHeavy chain 9Molecular determinantsChemical disruptionAmino acidsITPR3RaftsKidney cellsIntracellular CaFinal common eventReceptor type 3Release channelMYH9Inflammatory stress signaling via NF-kB alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells
Fowler JWM, Zhang R, Tao B, Boutagy NE, Sessa WC. Inflammatory stress signaling via NF-kB alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells. ELife 2022, 11: e79529. PMID: 35959888, PMCID: PMC9395194, DOI: 10.7554/elife.79529.Peer-Reviewed Original ResearchConceptsAcute inflammatory responseEndothelial cellsCholesterol homeostasisInflammatory stressInflammatory responsePro-inflammatory cytokinesSite of injuryCholesterol biosynthetic gene expressionNF-κB DNA bindingHuman endothelial cellsMultiple sclerosisInflammatory activationPrimary human endothelial cellsVascular endotheliumNF-κB-inducible genesTissue damageInducible targetAberrant activationRole of cholesterolSREBP2 activationMicrobial infectionsCholesterolKey transcription regulatorHomeostasisLeukocytes
2021
Characterization of a Novel Caveolin Modulator That Reduces Vascular Permeability and Ocular Inflammation
Bernatchez PN, Tao B, Bradshaw RA, Eveleth D, Sessa WC. Characterization of a Novel Caveolin Modulator That Reduces Vascular Permeability and Ocular Inflammation. Translational Vision Science & Technology 2021, 10: 21-21. PMID: 34111267, PMCID: PMC8132009, DOI: 10.1167/tvst.10.6.21.Peer-Reviewed Original ResearchConceptsOcular inflammationCell-permeable peptideRetinal damageVascular permeabilityModel of uveitisVascular endothelial growth factorNitric oxide releaseEndothelial growth factorNovel cell-permeable peptideEndothelial cell signalingVascular leakageClinical developmentInflammationOxide releaseEndothelial cellsNO releaseGrowth factorUveitisVEGFDistinct assaysPhage display technologyPresent studyVivoCell signalingPeptides
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