Titus Boggon, PhD
Associate Professor of Pharmacology and of Molecular Biophysics and BiochemistryCards
About
Research
Publications
2024
120 Treatable Acute Neuroinflammatory Disease Associated with Complement Factor I Loss-of-function in the Plain Community
Reid W, Carson V, Krieger P, Stiegler A, Boggon T, Sullivan K, van den Heuvel L, Romberg N. 120 Treatable Acute Neuroinflammatory Disease Associated with Complement Factor I Loss-of-function in the Plain Community. Clinical Immunology 2024, 262: 110062. DOI: 10.1016/j.clim.2024.110062.Peer-Reviewed Original ResearchDistinct functional constraints driving conservation of the cofilin N-terminal regulatory tail
Sexton J, Potchernikov T, Bibeau J, Casanova-Sepúlveda G, Cao W, Lou H, Boggon T, De La Cruz E, Turk B. Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail. Nature Communications 2024, 15: 1426. PMID: 38365893, PMCID: PMC10873347, DOI: 10.1038/s41467-024-45878-9.Peer-Reviewed Original ResearchConceptsN-terminal regionActin bindingSequence requirementsLIM kinaseAnalysis of individual variantsInactivates cofilinS. cerevisiaeRegulatory tailFamily proteinsActin depolymerizationPhosphorylation sitesKinase recognitionSequence variantsInhibitory phosphorylationCofilinN-terminusIndividual variantsFunctional constraintsActinDisordered sequencesPhosphorylationSequenceBiochemical analysisSequence constraintsKinase
2023
Autoregulation of the LIM kinases by their PDZ domain
Casanova-Sepúlveda G, Sexton J, Turk B, Boggon T. Autoregulation of the LIM kinases by their PDZ domain. Nature Communications 2023, 14: 8441. PMID: 38114480, PMCID: PMC10730565, DOI: 10.1038/s41467-023-44148-4.Peer-Reviewed Original ResearchMutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatientsCorrection: Rho family GTPase signaling through type II p21-activated kinases
Chetty A, Ha B, Boggon T. Correction: Rho family GTPase signaling through type II p21-activated kinases. Cellular And Molecular Life Sciences 2023, 80: 334. PMID: 37880444, PMCID: PMC11073300, DOI: 10.1007/s00018-023-04938-x.Peer-Reviewed Original ResearchStructure Determination of SH2–Phosphopeptide Complexes by X-Ray Crystallography: The Example of p120RasGAP
Stiegler A, Boggon T. Structure Determination of SH2–Phosphopeptide Complexes by X-Ray Crystallography: The Example of p120RasGAP. Methods In Molecular Biology 2023, 2705: 77-89. PMID: 37668970, PMCID: PMC11059313, DOI: 10.1007/978-1-0716-3393-9_5.Peer-Reviewed Original ResearchConceptsSrc homology 2SH2 domain bindsSH2 domainDomain bindsNew molecular-level insightsSH2 domain proteinsMolecular-level insightsX-ray crystallographyX-ray diffraction studiesDomain proteinsPartner proteinsHomology 2Three-dimensional structureMolecular detailsStructure determinationSuitable crystalsCanonical interactionsVapour-diffusion methodCareful structural analysisDrop vapor diffusion methodCrystallographic studiesCrystallography studiesSH2-phosphopeptide complexesDiffraction studiesP120RasGAPAuthor Correction: Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4)
Ha B, Yigit S, Natarajan N, Morse E, Calderwood D, Boggon T. Author Correction: Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4). Communications Biology 2023, 6: 794. PMID: 37524913, PMCID: PMC10390574, DOI: 10.1038/s42003-023-05176-4.Peer-Reviewed Original ResearchDiverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1
Vish K, Stiegler A, Boggon T. Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1. Journal Of Biological Chemistry 2023, 299: 105098. PMID: 37507023, PMCID: PMC10470053, DOI: 10.1016/j.jbc.2023.105098.Peer-Reviewed Original ResearchConceptsSH2 domainSpatial-temporal regulationDual SH2 domainsProper vascular developmentKey binding partnerProtein familySH2 interactionsBinding partnerHuman proteinsDistinct binding interactionsWeakened affinityVascular developmentRasGAPConformational differencesP190RhoGAPSmall-angle X-ray scatteringBindingBinding interactionsAffinity measurementsEphB4DomainGTPaseDok1X-ray scatteringProteinDe novo variants implicate chromatin modification, transcriptional regulation, and retinoic acid signaling in syndromic craniosynostosis
Timberlake A, McGee S, Allington G, Kiziltug E, Wolfe E, Stiegler A, Boggon T, Sanyoura M, Morrow M, Wenger T, Fernandes E, Caluseriu O, Persing J, Jin S, Lifton R, Kahle K, Kruszka P. De novo variants implicate chromatin modification, transcriptional regulation, and retinoic acid signaling in syndromic craniosynostosis. American Journal Of Human Genetics 2023, 110: 846-862. PMID: 37086723, PMCID: PMC10183468, DOI: 10.1016/j.ajhg.2023.03.017.Peer-Reviewed Original ResearchConceptsDamaging de novo variantsChromatin modificationsDe novo variantsCranial neural crest cellsGenome-wide significanceNeural crest cellsNovo variantsRetinoic acid receptor alphaExome sequence dataAcid receptor alphaTranscriptional regulationProband-parent triosGene transcriptionSequence dataCrest cellsOsteoblast differentiationCS phenotypeMendelian formsRecurrent gainsGenesRisk genesGenetic etiologyRetinoic acidReceptor alphaNeurodevelopmental disorders169 Exome Sequencing Implicates Endothelial Ras Signaling Network in Vein of Galen Aneurysmal Malformation
Mekbib K, Zhao S, Nelson-Williams C, Prendergast A, Zeng X, Rolle M, Shohfi J, Smith H, Ocken J, Moyer Q, Piwowarczyk P, Allington G, Dong W, van der Ent M, Chen D, Li B, Duran D, Mane S, Walcott B, Stapleton C, Aagaard-Kienitz B, Rodesch G, Jackson E, Smith E, Orbach D, Berenstein A, Bilguvar K, Zhao H, Erson-Omay Z, King P, Huttner A, Lifton R, Boggon T, Nicoli S, Jin S, Kahle K. 169 Exome Sequencing Implicates Endothelial Ras Signaling Network in Vein of Galen Aneurysmal Malformation. Neurosurgery 2023, 69: 22-22. DOI: 10.1227/neu.0000000000002375_169.Peer-Reviewed Original ResearchPathway analysisP120 Ras-GAPExome sequencingSevere vascular defectsGalen aneurysmal malformationReceptor tyrosine kinase activityTyrosine kinase activityDamaging de novoMutant embryosRas-GAPSignaling networksGenetic regulationRas activationAneurysmal malformationZebrafish modelDe novo mutationsKinase activityDisease genesAxon guidanceGenetic samplesWhole-exome sequencingHigh-output heart failureFunctional studiesCollected specimensSequencing