2022
Strategies for Glycoengineering Therapeutic Proteins
Dammen-Brower K, Epler P, Zhu S, Bernstein ZJ, Stabach PR, Braddock DT, Spangler JB, Yarema KJ. Strategies for Glycoengineering Therapeutic Proteins. Frontiers In Chemistry 2022, 10: 863118. PMID: 35494652, PMCID: PMC9043614, DOI: 10.3389/fchem.2022.863118.Peer-Reviewed Original Research
2020
Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering
Stabach PR, Zimmerman K, Adame A, Kavanagh D, Saeui CT, Agatemor C, Gray S, Cao W, De La Cruz EM, Yarema KJ, Braddock DT. Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering. Clinical And Translational Science 2020, 14: 362-372. PMID: 33064927, PMCID: PMC7877847, DOI: 10.1111/cts.12887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveDisease Models, AnimalEnzyme Replacement TherapyGlycosylationHalf-LifeHistocompatibility Antigens Class IHumansMaleMice, TransgenicPhosphoric Diester HydrolasesProtein EngineeringProtein Structure, TertiaryPyrophosphatasesReceptors, FcRecombinant Fusion ProteinsVascular CalcificationConceptsProtein engineeringO-BuN-glycansGlycosylation engineeringCellular recyclingENPP1-deficient miceTerminal sialylationBiomanufacturing platformProtein therapeuticsCalcification disordersSialylationCellsVivo activityFc neonatal receptorTherapeuticsArterial calcificationProteinMurine modelManNAcEnzyme replacementNeonatal receptorEfficacious levelsGeneral strategyThree-prong strategyDrug potency
2019
Protein Engineering and Glycan Optimization Improves Pharmicokinetics of an Enzyme Biologic 10‐fold
Braddock D, Stabach P, Zimmerman K, Kavanagh D, Sauei C, Yarema K. Protein Engineering and Glycan Optimization Improves Pharmicokinetics of an Enzyme Biologic 10‐fold. The FASEB Journal 2019, 33: 801.1-801.1. DOI: 10.1096/fasebj.2019.33.1_supplement.801.1.Peer-Reviewed Original ResearchFusion proteinProtein engineeringCHO cell linesCellular recyclingBioprocessing methodsRecombinant fusion proteinConsensus sequenceExtracellular domainSialic acidTertiary structureN-acetylmannosamineCHO cellsHuman alphaProteinCell linesFASEB JournalFc domainCell culture mediumCulture mediumGeneralized Arterial CalcificationENPP1
2013
Molecular Basis of Purinergic Signal Metabolism by Ectonucleotide Pyrophosphatase/Phosphodiesterases 4 and 1 and Implications in Stroke*♦
Albright RA, Ornstein DL, Cao W, Chang WC, Robert D, Tehan M, Hoyer D, Liu L, Stabach P, Yang G, De La Cruz EM, Braddock DT. Molecular Basis of Purinergic Signal Metabolism by Ectonucleotide Pyrophosphatase/Phosphodiesterases 4 and 1 and Implications in Stroke*♦. Journal Of Biological Chemistry 2013, 289: 3294-3306. PMID: 24338010, PMCID: PMC3916532, DOI: 10.1074/jbc.m113.505867.Peer-Reviewed Original ResearchConceptsExtracellular membrane proteinsMembrane proteinsSubstrate specificityMolecular basisHigh-resolution crystal structuresResolution crystal structureComparative structural analysisATP hydrolysisNPP1Brain vascular endotheliumCorresponding regionTerminal phosphateLow nanomolar concentrationsPurinergic signalsPlatelet aggregationProteinATPEnzymeNanomolar concentrationsVascular endotheliumPhosphodiesterases 4Ap3AMetabolismSurface of chondrocytesTissue mineralization
2005
Neutrophils Lacking Platelet-Endothelial Cell Adhesion Molecule-1 Exhibit Loss of Directionality and Motility in CXCR2-Mediated Chemotaxis
Wu Y, Stabach P, Michaud M, Madri JA. Neutrophils Lacking Platelet-Endothelial Cell Adhesion Molecule-1 Exhibit Loss of Directionality and Motility in CXCR2-Mediated Chemotaxis. The Journal Of Immunology 2005, 175: 3484-3491. PMID: 16148090, DOI: 10.4049/jimmunol.175.6.3484.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell ShapeChemokine CXCL1ChemokinesChemokines, CXCChemotaxis, LeukocyteCytokinesInterleukin-8Intracellular Signaling Peptides and ProteinsMiceMice, KnockoutNeutrophilsPlatelet Endothelial Cell Adhesion Molecule-1Protein Phosphatase 1Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesReceptors, Interleukin-8BConceptsCell motilitySrc homology 2 domainF-actinSHP-1 phosphatase activityWild-type neutrophilsF-actin polymerizationPhosphatase 1Time-lapse videomicroscopyPECAM-1Cytokine-induced mobilizationPhosphatase activityExhibit lossMurine neutrophilsMotilityChemotaxisZigmond chamberCellsPECAMLeading frontCytoskeletonMoesinIL-8FMLP gradientProteinActin
1998
ADP ribosylation factor regulates spectrin binding to the Golgi complex
Godi A, Santone I, Pertile P, Devarajan P, Stabach P, Morrow J, Di Tullio G, Polishchuk R, Petrucci T, Luini A, De Matteis M. ADP ribosylation factor regulates spectrin binding to the Golgi complex. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 8607-8612. PMID: 9671725, PMCID: PMC21123, DOI: 10.1073/pnas.95.15.8607.Peer-Reviewed Original ResearchConceptsADP-ribosylation factorGolgi complexRibosylation factorG proteinsVesicular stomatitis virus G proteinPleckstrin homology domainSmall G proteinsPH domain interactionBinding of spectrinVirus G proteinGolgi spectrinHomology domainPH domainCoat proteinDocking siteDomain interactionsGolgiEndoplasmic reticulumPtdInsP2 levelsDomain IPhospholipase DSpectrinGolgi fractionsProteinPtdInsP2