Featured Publications
Catalysis‐Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass
Zimmerman K, Liu X, von Kroge S, Stabach P, Lester ER, Chu EY, Srivastava S, Somerman MJ, Tommasini SM, Busse B, Schinke T, Carpenter TO, Oheim R, Braddock DT. Catalysis‐Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass. Journal Of Bone And Mineral Research 2020, 37: 1733-1749. PMID: 35773783, PMCID: PMC9709593, DOI: 10.1002/jbmr.4640.Peer-Reviewed Original ResearchConceptsHeterotopic mineralizationBone massFibroblast growth factor 23Growth factor 23Low bone massSoft tissue calcificationEarly-onset osteoporosisFrizzled-related protein 1Soluble Wnt inhibitorsTrabecular bone microarchitectureENPP1 deficiencyΒ-catenin signalingFactor 23Plasma FGF23Vascular calcificationArterial calcificationNuclear β-cateninPlasma PPiBone microarchitectureMurine modelTissue calcificationPlasma PiWnt inhibitorsCalcificationMiceResponse of enthesopathy in ENPP1 deficiency to enzyme replacement therapy in murine models and enthesopathy comorbidities and quality of life in ENPP1‐deficient adults
Ansh A, Nester C, O'Brien C, Stabach P, Murtada S, Lester E, Khursigara G, Molloy L, Carpenter T, Ferreira C, Braddock D. Response of enthesopathy in ENPP1 deficiency to enzyme replacement therapy in murine models and enthesopathy comorbidities and quality of life in ENPP1‐deficient adults. The FASEB Journal 2022, 36 DOI: 10.1096/fasebj.2022.36.s1.r5311.Peer-Reviewed Original ResearchENPP1 deficiencyQuality of lifeMusculoskeletal complicationsReplacement therapyBrief Pain Inventory-Short FormPhysical Function Short FormAchilles tendon calcificationHealth-related qualityMajority of patientsCervical spine fusionPresence of enthesopathyAnalgesic medicationRegular chowResidual painAdult patientsDose escalationPhysical functionCardiovascular calcificationTendon calcificationAchilles tendonSpine fusionMurine modelHypophosphatemic ricketsEnzyme replacementPatientsIdentification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early‐Onset Osteoporosis
Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, Koga M, Taniguchi Y, Uchida T, Yamaguchi H, Niida Y, Nakazato M, Nangaku M, Makita N, Takamura T, Saito T, Braddock DT, Ito N. Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early‐Onset Osteoporosis. Journal Of Bone And Mineral Research 2020, 37: 1125-1135. PMID: 35340077, PMCID: PMC9177665, DOI: 10.1002/jbmr.4550.Peer-Reviewed Original ResearchConceptsAutosomal recessive hypophosphatemic rickets type 2Diffuse idiopathic skeletal hyperostosisEarly-onset osteoporosisENPP1 variantsHypophosphatemic ricketsENPP1 mutationsFibroblast growth factor 23Case 1Growth factor 23Serum phosphate levelsIdiopathic skeletal hyperostosisPosterior longitudinal ligamentCase 3Spinal ligament ossificationFactor 23Skeletal hyperostosisArterial calcificationLongitudinal ligamentPresumptive diagnosisLigament ossificationSevere ossificationMutational statusType 2Pathogenic lossGenetic testing
2024
Effect of Mutation Type on Ectopic Ossification Among Adult Patients With X-Linked Hypophosphatemia
Kato H, Ishihara Y, Ohata Y, Irie K, Watanabe S, Kimura S, Hoshino Y, Hidaka N, Kinoshita Y, Taniguchi Y, Kobayashi H, Braddock D, Kubota T, Ozono K, Nangaku M, Makita N, Ito N. Effect of Mutation Type on Ectopic Ossification Among Adult Patients With X-Linked Hypophosphatemia. Journal Of The Endocrine Society 2024, 8: bvae184. PMID: 39498416, PMCID: PMC11532897, DOI: 10.1210/jendso/bvae184.Peer-Reviewed Original ResearchX-linked hypophosphatemiaNonsense-mediated decayEctopic ossificationPathogenic variantsSpinal computed tomography scansMutation typeInhibitor of tissue calcificationComputed tomography scanSpinal ligament ossificationGenotype-phenotype correlationKellgren-Lawrence classificationNon-consanguineous familyPHEX mutationsPHEX variantAdult patientsTomography scanLigament ossificationFibroblast growth factorYellow ligamentOS indexKellgren-LawrenceStudy populationTissue calcificationPatientsProtein functionCorrection of Paradoxical Mineralization in Murine CKD-MBD by ENPP1 Enzyme Biologics
Kato H, Kim H, Ishaq T, Sims D, Srivastava S, Stabach P, Carpenter T, O'Neill W, Braddock D. Correction of Paradoxical Mineralization in Murine CKD-MBD by ENPP1 Enzyme Biologics. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.2024sre0cym1. DOI: 10.1681/asn.2024sre0cym1.Peer-Reviewed Original ResearchNovel treatment for PXE: Recombinant ENPP1 enzyme therapy
Jacobs I, Obiri-Yeboah D, Stabach P, Braddock D, Li Q. Novel treatment for PXE: Recombinant ENPP1 enzyme therapy. Molecular Therapy 2024, 32: 3815-3820. PMID: 39342427, PMCID: PMC11573614, DOI: 10.1016/j.ymthe.2024.09.028.Peer-Reviewed Original ResearchAbcc6<sup>-/-</sup> micePseudoxanthoma elasticumAbcc6<sup>-/-</sup> mouse model of pseudoxanthoma elasticumPPi levelsMouse model of pseudoxanthoma elasticumModel of pseudoxanthoma elasticumEnzyme therapyEctopic calcificationPlasma PPi levelsMuzzle skinDose-dependent elevationHepatic efflux transportersPrevent ectopic calcificationPlasma PPiABCC6 geneATP secretionTherapeutic optionsDose-dependentlyEfflux transportersInactivating mutationsENPP1 activitySubcutaneous injectionWeeks of ageNovel treatmentCalcification disordersA dual-acting DNASE1/DNASE1L3 biologic prevents autoimmunity and death in genetic and induced lupus models
Stabach P, Sims D, Gomez-Bañuelos E, Zehentmeier S, Dammen-Brower K, Bernhisel A, Kujawski S, Lopez S, Petri M, Goldman D, Lester E, Le Q, Ishaq T, Kim H, Srivastava S, Kumar D, Pereira J, Yarema K, Koumpouras F, Andrade F, Braddock D. A dual-acting DNASE1/DNASE1L3 biologic prevents autoimmunity and death in genetic and induced lupus models. JCI Insight 2024, 9: e177003. PMID: 38888971, PMCID: PMC11383374, DOI: 10.1172/jci.insight.177003.Peer-Reviewed Original ResearchSystemic lupus erythematosusDNASE1L3 deficiencySporadic systemic lupus erythematosusAssociated with systemic lupus erythematosusChromatin degradationDNA accumulationDevelopment of lupusPristane-induced lupusSelf-DNACell free DNAHuman isoformsSystemic lupus erythematosus plasmasDouble knockout miceDNASE1L3Pathogenic effectsFree DNALupus modelEnzymeInducible lupus modelAdult patientsLupus erythematosusKnockout micePediatric populationAutoimmune diseasesDNAQuantitative correlation of ENPP1 pathogenic variants with disease phenotype
Ansh A, Stabach P, Ciccone C, Cao W, De La Cruz E, Sabbagh Y, Carpenter T, Ferreira C, Braddock D. Quantitative correlation of ENPP1 pathogenic variants with disease phenotype. Bone 2024, 186: 117136. PMID: 38806089, PMCID: PMC11227391, DOI: 10.1016/j.bone.2024.117136.Peer-Reviewed Original ResearchEctonucleotide pyrophosphatase/phosphodiesterase 1Pathogenic variantsDisease phenotypeEnzyme velocityCompound heterozygotesEnzyme activityVariable enzyme activityAutosomal dominant phenotypeHigh-throughput assayAutosomal recessive formInnate immune responseENPP1 variantsDamaging variantsENPP1 deficiencyCole diseaseDominant phenotypeAutosomal dominant diseaseCatalytic velocityRecessive formEnzymePhenotypeWT levelsBio-active moleculesClinical phenotypeDominant disease
2023
ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency
Ferreira C, Carpenter T, Braddock D. ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency. Annual Review Of Pathology Mechanisms Of Disease 2023, 19: 507-540. PMID: 37871131, PMCID: PMC11062289, DOI: 10.1146/annurev-pathmechdis-051222-121126.Peer-Reviewed Original ResearchGeneral medical populationENPP1 deficiencyMedical populationsEctonucleotide pyrophosphatase/phosphodiesteraseSoft tissue diseaseEarly-onset osteoporosisMiddle-aged adultsClinical presentationTissue diseaseVascular calcificationArterial calcificationBedside developmentRare diseaseMineralization disordersLarge arteriesPyrophosphatase/phosphodiesteraseClinical phenotypeExtracellular ATPSoft tissuePathophysiologyAdenosine monophosphateDiseaseCalcificationTransmembrane glycoproteinDeficiencyHypophosphatemic rickets: An unexplained early feature of craniometaphyseal dysplasia
Barros J, Braddock D, Carpenter T. Hypophosphatemic rickets: An unexplained early feature of craniometaphyseal dysplasia. Bone Reports 2023, 19: 101707. PMID: 37654679, PMCID: PMC10466911, DOI: 10.1016/j.bonr.2023.101707.Peer-Reviewed Original ResearchMonths of ageCraniometaphyseal dysplasiaLow serum phosphorusElevated serum alkaline phosphatase activityHeterozygous pathogenic variantsSerum alkaline phosphatase activityHigh tubular reabsorptionProgressive hyperostosisSecondary hyperparathyroidismRadiographic improvementSerum phosphorusTubular reabsorptionRadiographic changesCranial nervesEarly featureMetaphyseal flaringPathogenic variantsDysplasiaRicketsSkeletal dysplasiaBiochemical profileMonthsLong bonesCraniofacial bonesAge 1Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments
Kato H, Braddock D, Ito N. Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments. Current Osteoporosis Reports 2023, 21: 552-566. PMID: 37530996, PMCID: PMC10543536, DOI: 10.1007/s11914-023-00814-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDiffuse idiopathic skeletal hyperostosisAutosomal recessive hypophosphatemic rickets type 2Idiopathic skeletal hyperostosisSkeletal hyperostosisOPLL patientsGenetic factorsPathogenic variantsFibroblast growth factor 23Growth factor 23Posterior longitudinal ligamentSpinal ligament ossificationRecent FindingsRecent studiesStrong genetic factorImportant new biomarkerDisease courseFactor 23Longitudinal ligamentClinical evaluationPlasma biomarkersClinical trialsLigament ossificationPlasma PPiCalcification disordersPatientsEctopic calcificationIRF8 may be a useful marker for blastic plasmacytoid dendritic cell neoplasm, especially with weak CD123 expression
Tang H, Panse G, Braddock D, Perincheri S, Xu M, McNiff J. IRF8 may be a useful marker for blastic plasmacytoid dendritic cell neoplasm, especially with weak CD123 expression. Journal Of Cutaneous Pathology 2023, 50: 595-600. PMID: 37082914, DOI: 10.1111/cup.14439.Peer-Reviewed Original ResearchConceptsBlastic plasmacytoid dendritic cell neoplasmPlasmacytoid dendritic cell neoplasmDendritic cell neoplasmPunch biopsy specimenBiopsy specimenCell neoplasmsCase of BPDCNUseful markerTumor cellsTCL-1 expressionAtypical mononuclear cellsBone marrow involvementDiffuse dermal infiltrateDendritic cell lineagePotential diagnostic pitfallRegulatory factor 8TCL-1BPDCN casesCD123 expressionMarrow involvementDermal infiltrateCutaneous nodulesMyelodysplastic syndromeSkin nodulesMononuclear cellsLonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome
Murtada S, Mikush N, Wang M, Ren P, Kawamura Y, Ramachandra A, Li D, Braddock D, Tellides G, Gordon L, Humphrey J. Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome. ELife 2023, 12: e82728. PMID: 36930696, PMCID: PMC10023154, DOI: 10.7554/elife.82728.Peer-Reviewed Original ResearchConceptsMouse modelLeft ventricular diastolic functionHutchinson-Gilford progeria syndromeVentricular diastolic functionPulse wave velocityDrug-associated effectsMTOR inhibitor rapamycinCardiovascular sequelaeDiastolic functionProgeria syndromeDevastating conditionCardiac functionCardiovascular functionClinical trialsCardiovascular diseaseMuscular arteriesUS FoodDrug AdministrationProgeria miceArterial structurePremature deathLonafarnibCardiovascular structureCharacteristics of agingInhibitor rapamycin
2022
Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI)
Theng EH, Brewer CC, Oheim R, Zalewski CK, King KA, Delsmann MM, Rolvien T, Gafni RI, Braddock DT, Jeffrey Kim H, Ferreira CR. Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI). Orphanet Journal Of Rare Diseases 2022, 17: 273. PMID: 35854274, PMCID: PMC9295326, DOI: 10.1186/s13023-022-02410-w.Peer-Reviewed Original ResearchConceptsOssicular chain dysfunctionGeneralized Arterial CalcificationOtitis mediaArterial calcificationPrevalence of HLRecurrent otitis mediaTerms of patientTemporal bone imagingEtiology of HLBasic science laboratoryAuricular calcificationConductive HLHL etiologyOtologic featuresDegree of HLCohort studyOtologic evaluationRadiologic featuresAudiological assessmentAuditory dysfunctionTube placementRecurrent episodesBilateral HLCranial CTLikely multifactorialSystematic characterization of enzyme activity on ENPP1 deficiency disease phenotype
Ansh A, Stabach P, Carpenter T, Ferreira C, Braddock D. Systematic characterization of enzyme activity on ENPP1 deficiency disease phenotype. The FASEB Journal 2022, 36 DOI: 10.1096/fasebj.2022.36.s1.r5223.Peer-Reviewed Original ResearchStrategies 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 ResearchThe cardiomyocyte disrupts pyrimidine biosynthesis in non-myocytes to regulate heart repair
Li S, Yokota T, Wang P, Hoeve J, Ma F, Le TM, Abt ER, Zhou Y, Wu R, Nanthavongdouangsy M, Rodriguez A, Wang Y, Lin YJ, Muranaka H, Sharpley M, Braddock DT, MacRae VE, Banerjee U, Chiou PY, Seldin M, Huang D, Teitell M, Gertsman I, Jung M, Bensinger SJ, Damoiseaux R, Faull K, Pellegrini M, Lusis A, Graeber TG, Radu CG, Deb A. The cardiomyocyte disrupts pyrimidine biosynthesis in non-myocytes to regulate heart repair. Journal Of Clinical Investigation 2022, 132: e149711. PMID: 34813507, PMCID: PMC8759793, DOI: 10.1172/jci149711.Peer-Reviewed Original ResearchConceptsCardiac injuryHeart repairENPP1 inhibitorsPyrimidine biosynthesisHeart injuryIschemic cardiac injuryAdministration of uridineEctonucleotide pyrophosphatase/phosphodiesterase 1Augmenting tissue repairP53-mediated cell deathSmall molecule screeningCardiac muscle cellsPyrophosphatase/phosphodiesterase 1Systemic administrationNonmyocyte cellsMurine modelHeart functionCardiac repairGenotoxic stressInjuryIntercellular regulationMuscle cellsPopulation of cellsExtracellular ATPMolecule screening
2021
Direct targeting of amplified gene loci for proapoptotic anticancer therapy
Kaushik Tiwari M, Colon-Rios DA, Tumu HCR, Liu Y, Quijano E, Krysztofiak A, Chan C, Song E, Braddock DT, Suh HW, Saltzman WM, Rogers FA. Direct targeting of amplified gene loci for proapoptotic anticancer therapy. Nature Biotechnology 2021, 40: 325-334. PMID: 34711990, PMCID: PMC8930417, DOI: 10.1038/s41587-021-01057-5.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksTriplex-forming oligonucleotidesDNA damage responseDouble-strand breaksDrug resistanceGene amplificationP53-independent apoptosisHER2-positive breastOvarian cancer modelHuman tumor xenograftsInduction of apoptosisGenomic lociNumber of drugsCellular functionsDamage responseGene locusProtein productsHER2-positive cancer cellsDriver genesClinical efficacyCombat drug resistanceDNA damageHER2 amplificationTherapeutic strategiesTumor xenograftsPlacenta-derived interferon-stimulated gene 20 controls ZIKA virus infection
Ding J, Aldo P, Roberts CM, Stabach P, Liu H, You Y, Qiu X, Jeong J, Maxwell A, Lindenbach B, Braddock D, Liao A, Mor G. Placenta-derived interferon-stimulated gene 20 controls ZIKA virus infection. EMBO Reports 2021, 22: embr202152450. PMID: 34405956, PMCID: PMC8490983, DOI: 10.15252/embr.202152450.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionTrophoblast cellsPotential immune modulatory functionsInterferon-stimulated gene 20Anti-viral treatmentHigh-risk populationImmune modulatory functionsAnti-viral responseZika viral infectionImportance of preventionPregnant womenReplacement therapyViral infectionFetal developmentZika virusViral titersModulatory functionViral replicationInfectionAdverse effectsGene 20PregnancyPlacentaRNA virusesSimultaneous colonic T-cell lymphoma and graft-versus-host disease: A rare diagnosis
Gisriel S, Hung K, Braddock D, Seropian S, Foss F, Robert M, Xu M. Simultaneous colonic T-cell lymphoma and graft-versus-host disease: A rare diagnosis. Human Pathology Reports 2021, 24: 200507. DOI: 10.1016/j.ehpc.2021.200507.Peer-Reviewed Case Reports and Technical NotesCutaneous T-cell lymphomaT-cell lymphomaPost-transplant lymphoproliferative disorderAllogeneic stem cell transplantAtypical lymphoid infiltrateStem cell transplantCritical clinical implicationsLimited tissue samplesAbdominal painHost diseaseGastrointestinal biopsiesLymph nodesCell transplantLymphoid infiltratesLymphoproliferative disordersMycosis fungoidesRare diagnosisDiagnostic workupDifferential diagnosisIntestinal mucosaClinical implicationsTissue samplesLymphomaGraftDiagnosis