Featured Publications
Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K
Lucas CL, Zhang Y, Venida A, Wang Y, Hughes J, McElwee J, Butrick M, Matthews H, Price S, Biancalana M, Wang X, Richards M, Pozos T, Barlan I, Ozen A, Rao VK, Su HC, Lenardo MJ. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. Journal Of Experimental Medicine 2014, 211: 2537-2547. PMID: 25488983, PMCID: PMC4267241, DOI: 10.1084/jem.20141759.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlternative SplicingAntibody FormationBase SequenceCatalytic DomainCD8-Positive T-LymphocytesCell DifferentiationChild, PreschoolClass Ia Phosphatidylinositol 3-KinaseEnzyme ActivationExonsFemaleGenes, DominantHeterozygoteHumansImmunologic Deficiency SyndromesLymphoproliferative DisordersMaleMolecular Sequence DataMutationPedigreePhosphatidylinositol 3-KinasesProtein Structure, TertiarySequence DeletionSignal TransductionTelomereTOR Serine-Threonine KinasesConceptsT cellsPI3KPI3K subunitsSenescent T cellsRecurrent sinopulmonary infectionsHeterozygous splice site mutationSplice site mutationEffector cellsPeripheral bloodSinopulmonary infectionsHuman immunodeficiencyHeterozygous splice mutationsImmunodeficiency diseaseHealthy subjectsUnique disorderHeterozygous mutationsClass IaPatient cellsProminent expansionK subunitLymphoproliferationPatientsSimilar diseasesShort telomeresDisease
2021
Infections in activated PI3K delta syndrome (APDS)
Brodsky NN, Lucas CL. Infections in activated PI3K delta syndrome (APDS). Current Opinion In Immunology 2021, 72: 146-157. PMID: 34052541, DOI: 10.1016/j.coi.2021.04.010.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPI3K delta syndromeHematopoietic stem cell transplantAnti-microbial prophylaxisPI3K-delta syndromeStem cell transplantSenescent T cellsSpectrum of infectionsAdaptive immune functionAutosomal dominant disorderCell transplantImmune defectsImmunoglobulin replacementRecurrent infectionsImmunomodulatory agentsTherapy optionsT cellsImmune functionInfection susceptibilityInborn errorsDominant disorderInfectionLymphadenopathyPatientsFunction mutationsImmunodeficiency
2017
Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib
Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C. Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib. Blood 2017, 130: 2307-2316. PMID: 28972011, PMCID: PMC5701526, DOI: 10.1182/blood-2017-08-801191.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokinesChildChild, PreschoolClass I Phosphatidylinositol 3-KinasesDemographyDose-Response Relationship, DrugFemaleHumansImmunoglobulin MImmunologic Deficiency SyndromesInfantLymph NodesLymphocyte ActivationMaleMolecular Targeted TherapyMutationOrgan SizePhenotypePrimary Immunodeficiency DiseasesProtein Kinase InhibitorsPyridinesPyrimidinesRatsSpleenT-LymphocytesTOR Serine-Threonine KinasesTransfectionConceptsImmune dysregulationT cellsB cellsElevated serum immunoglobulin MPI3K/Akt pathway activityDose-escalation studyLymph node sizeSenescent T cellsWeeks of treatmentDose-dependent suppressionTransitional B cellsTumor necrosis factorDose-dependent reductionPrecision medicine therapiesSerum immunoglobulin MNaive B cellsT cell blastsAkt pathway activityAPDS patientsPI3Kδ pathwayInflammatory markersPD-1Clinical parametersSpleen volumeImmune deficiency