Featured Publications
Determining the serotype composition of mixed samples of pneumococcus using whole-genome sequencing
Knight JR, Dunne EM, Mulholland EK, Saha S, Satzke C, Tothpal A, Weinberger DM. Determining the serotype composition of mixed samples of pneumococcus using whole-genome sequencing. Microbial Genomics 2020, 7: mgen000494. PMID: 33355528, PMCID: PMC8115901, DOI: 10.1099/mgen.0.000494.Peer-Reviewed Original ResearchIntegrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis
Farshidfar F, Rhrissorrakrai K, Levovitz C, Peng C, Knight J, Bacchiocchi A, Su J, Yin M, Sznol M, Ariyan S, Clune J, Olino K, Parida L, Nikolaus J, Zhang M, Zhao S, Wang Y, Huang G, Wan M, Li X, Cao J, Yan Q, Chen X, Newman AM, Halaban R. Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis. Nature Communications 2022, 13: 898. PMID: 35197475, PMCID: PMC8866401, DOI: 10.1038/s41467-022-28566-4.Peer-Reviewed Original ResearchConceptsAcral melanomaMelanoma subtypesClinical profilingCommon melanoma subtypeImmune checkpoint blockadeCheckpoint blockadeInferior survivalMelanoma cell linesKey molecular driversPoor prognosisTherapeutic targetAnchorage-independent growthImmunomodulatory genesNon-white individualsHotspot mutationsMolecular driversCandidate oncogeneMelanomaApoptotic cell deathLZTR1Focal amplificationTumor promoterCell linesMetastasisTumor suppressorUnexplained Female Infertility Associated with Genetic Disease Variants
Dougherty M, Poch A, Chorich L, Hawkins Z, Xu H, Roman R, Liu H, Brakta S, Taylor H, Knight J, Kim H, Diamond M, Layman L. Unexplained Female Infertility Associated with Genetic Disease Variants. New England Journal Of Medicine 2023, 388: 1055-1056. PMID: 36920765, PMCID: PMC10134047, DOI: 10.1056/nejmc2211539.Peer-Reviewed Original Research
2024
Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome
Brakta S, Du Q, Chorich L, Hawkins Z, Sullivan M, Ko E, Kim H, Knight J, Taylor H, Friez M, Phillips J, Layman L. Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome. Molecular And Cellular Endocrinology 2024, 589: 112237. PMID: 38599276, DOI: 10.1016/j.mce.2024.112237.Peer-Reviewed Original ResearchCNV regionsDetect intragenic deletionsSingle nucleotide variantsRecurrent deletion regionsC-terminal regionSequencing of familiesGenome sequenceNucleotide variantsProtein expression in vitroLXXLL sequenceMissense variantsDeleted regionChromosome 17q12Exome sequencingGenetic approachesIntragenic deletionsTruncating variantsSanger sequencingSplice variantsMolecular basisHeterozygous variantsStopgain variantsZNHIT3Steroid hormone bindingExpression in vitroAuto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan.
Ryu HY, Jeong DW, Kim SY, Jeoung SW, Zhao D, Knight J, Lam T, Jin JH, Lee HS, Hochstrasser M. Auto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan. Res Sq 2024 PMID: 38562857, DOI: 10.21203/rs.3.rs-4016606/v1.Peer-Reviewed Original ResearchLow-frequency inherited complement receptor variants are associated with purpura fulminans.
Bendapudi PK, Nazeen S, Ryu J, Söylemez O, Robbins A, Rouaisnel B, O'Neil JK, Pokhriyal R, Yang M, Colling M, Pasko B, Bouzinier M, Tomczak L, Collier L, Barrios D, Ram S, Toth-Petroczy A, Krier J, Fieg E, Dzik WH, Hudspeth JC, Pozdnyakova O, Nardi V, Knight J, Maas R, Sunyaev S, Losman JA. Low-frequency inherited complement receptor variants are associated with purpura fulminans. Blood 2024, 143: 1032-1044. PMID: 38096369, DOI: 10.1182/blood.2023021231.Peer-Reviewed Original ResearchActivated sputum eosinophils associated with exacerbations in children on mepolizumab
Wilson G, Knight J, Liu Q, Shelar A, Stewart E, Wang X, Yan X, Sanders J, Visness C, Gill M, Gruchalla R, Liu A, Kattan M, Khurana Hershey G, Togias A, Becker P, Altman M, Busse W, Jackson D, Montgomery R, Chupp G. Activated sputum eosinophils associated with exacerbations in children on mepolizumab. Journal Of Allergy And Clinical Immunology 2024, 154: 297-307.e13. PMID: 38485057, PMCID: PMC11305967, DOI: 10.1016/j.jaci.2024.01.031.Peer-Reviewed Original ResearchAirway eosinophilsSputum eosinophilsPatients treated with mepolizumabPlacebo-controlled clinical trialAnti-IL-5 treatmentEffect of mepolizumabEosinophil subpopulationsSevere eosinophilic asthmaAnti-interleukin-5Expression of CD62LFrequency of exacerbationsEosinophilic asthmaActivation markersSputum samplesUnsupervised cluster analysisMepolizumabTreatment armsReduce exacerbationsCD62LClinical trialsExacerbationMass cytometryEosinophilsExacerbation riskIntracellular markers
2023
Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas
Youngblood M, Erson-Omay Z, Li C, Najem H, Coșkun S, Tyrtova E, Montejo J, Miyagishima D, Barak T, Nishimura S, Harmancı A, Clark V, Duran D, Huttner A, Avşar T, Bayri Y, Schramm J, Boetto J, Peyre M, Riche M, Goldbrunner R, Amankulor N, Louvi A, Bilgüvar K, Pamir M, Özduman K, Kilic T, Knight J, Simon M, Horbinski C, Kalamarides M, Timmer M, Heimberger A, Mishra-Gorur K, Moliterno J, Yasuno K, Günel M. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas. Nature Communications 2023, 14: 6279. PMID: 37805627, PMCID: PMC10560290, DOI: 10.1038/s41467-023-41926-y.Peer-Reviewed Original ResearchIntegrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma
Chong M, Knight J, Peng G, Ji W, Chai H, Lu Y, Wu S, Li P, Hu Q. Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma. Cancer Genetics 2023, 276: 30-35. PMID: 37418972, DOI: 10.1016/j.cancergen.2023.06.002.Peer-Reviewed Original ResearchConceptsTumor mutation burdenWhole-exome sequencingGrade IIIHepatocellular carcinomaCNA burdenCase seriesBarcelona Clinic Liver Cancer stageExome sequencingBCLC stage CLiver Cancer stageEdmondson-Steiner gradingLarge case seriesGenetic defectsHigher CNA burdenAdjacent nontumor tissuesΒ-catenin pathwayBetter prognosisClinicopathologic findingsPoor prognosisClinicopathologic classificationCancer stageSurvival statusMutation burdenStage CPrognostic predictionTranscriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection
Agidigbi T, Kwon H, Knight J, Zhao D, Lee F, Oh I. Transcriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection. Frontiers In Cellular And Infection Microbiology 2023, 13: 1198115. PMID: 37434783, PMCID: PMC10332306, DOI: 10.3389/fcimb.2023.1198115.Peer-Reviewed Original ResearchConceptsDiabetic foot ulcersPeripheral blood mononuclear cellsHost immune responseActive infectionImmune responseDiabetic foot ulcer infectionsInfected diabetic foot ulcersFoot ulcer infectionsPatients 8 weeksIntravenous antibiotic therapyBlood mononuclear cellsWound healing statusDFU infectionsPBMC expressionSalvage therapyUlcer infectionDifferent time pointsAntibiotic therapyMajor complicationsSurgical treatmentFoot ulcersMononuclear cellsPotential intervention optionsSpecies-specific infectionTreatment responseHERV1-env Induces Unfolded Protein Response Activation in Autoimmune Liver Disease: A Potential Mechanism for Regulatory T Cell Dysfunction.
Subramanian K, Paul S, Libby A, Patterson J, Arterbery A, Knight J, Castaldi C, Wang G, Avitzur Y, Martinez M, Lobritto S, Deng Y, Geliang G, Kroemer A, Fishbein T, Mason A, Dominguez-Villar M, Mariappan M, Ekong U. HERV1-env Induces Unfolded Protein Response Activation in Autoimmune Liver Disease: A Potential Mechanism for Regulatory T Cell Dysfunction. The Journal Of Immunology 2023, 210: 732-744. PMID: 36722941, PMCID: PMC10691554, DOI: 10.4049/jimmunol.2100186.Peer-Reviewed Original ResearchConceptsAutoimmune hepatitisDe novo autoimmune hepatitisRegulatory T cell dysfunctionUnfolded protein responseNovo autoimmune hepatitisTregs of patientsAutoimmune liver diseaseIL-17A productionRegulatory T cellsT cell dysfunctionTreg suppressive functionExpression of RORCER stressEndoplasmic reticulum stressTreg plasticityLiver diseaseCell dysfunctionProtein response activationT cellsUnfolded protein response activationSuppressive functionIncreased expressionEffector propertiesReticulum stressPotential mechanismsMultiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts
Kundishora A, Allington G, McGee S, Mekbib K, Gainullin V, Timberlake A, Nelson-Williams C, Kiziltug E, Smith H, Ocken J, Shohfi J, Allocco A, Duy P, Elsamadicy A, Dong W, Zhao S, Wang Y, Qureshi H, DiLuna M, Mane S, Tikhonova I, Fu P, Castaldi C, López-Giráldez F, Knight J, Furey C, Carter B, Haider S, Moreno-De-Luca A, Alper S, Gunel M, Millan F, Lifton R, Torene R, Jin S, Kahle K. Multiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts. Nature Medicine 2023, 29: 667-678. PMID: 36879130, DOI: 10.1038/s41591-023-02238-2.Peer-Reviewed Original ResearchConceptsArachnoid cystCerebral arachnoid cystsDe novo variantsAC pathogenesisDevelopmental brain lesionsStructural brain diseaseAppropriate clinical contextPatients' medical recordsDamaging de novo variantsMedical recordsClinical severityBrain lesionsHealthy individualsAC subtypesBrain diseasesGenetic testingNeurodevelopmental pathologyClinical contextPathogenesisPatient phenotypesNeurodevelopmental programsNovo variantsRNA sequencing transcriptomeHuman brainCysts
2022
Application of multiplex amplicon deep-sequencing (MAD-seq) to screen for putative drug resistance markers in the Necator americanus isotype-1 β-tubulin gene
George S, Suwondo P, Akorli J, Otchere J, Harrison LM, Bilguvar K, Knight JR, Humphries D, Wilson MD, Caccone A, Cappello M. Application of multiplex amplicon deep-sequencing (MAD-seq) to screen for putative drug resistance markers in the Necator americanus isotype-1 β-tubulin gene. Scientific Reports 2022, 12: 11459. PMID: 35794459, PMCID: PMC9259660, DOI: 10.1038/s41598-022-15718-1.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsPeriodic mass drug administrationHigh-risk groupCross-sectional studyDrug resistance markersMass drug administrationResistance-associated mutationsHookworm Necator americanusPost-treatment samplesIsotype-1 β-tubulin geneHookworm infectionPersistent infectionResistance markersDrug AdministrationNecator americanusInfection statusVeterinary nematodesInfectionMarkersNucleotide polymorphismsSensitive toolBenzimidazole drugsNucleotide alleles
2021
Long-read single molecule real-time (SMRT) sequencing of GBA1 locus in Gaucher disease national cohort from Argentina reveals high frequency of complex allele underlying severe skeletal phenotypes: Collaborative study from the Argentine Group for Diagnosis and Treatment of Gaucher Disease
Drelichman G, Escobar N, Soberon B, Basack N, Frabasil J, Schenone A, Aguilar G, Larroudé M, Knight J, Zhao D, Ruan J, Mistry PK, Disease A. Long-read single molecule real-time (SMRT) sequencing of GBA1 locus in Gaucher disease national cohort from Argentina reveals high frequency of complex allele underlying severe skeletal phenotypes: Collaborative study from the Argentine Group for Diagnosis and Treatment of Gaucher Disease. Molecular Genetics And Metabolism Reports 2021, 29: 100820. PMID: 34820281, PMCID: PMC8600149, DOI: 10.1016/j.ymgmr.2021.100820.Peer-Reviewed Original ResearchSevere skeletal manifestationsDiagnóstico y tratamientoSevere skeletal phenotypeGenotype/phenotype correlationGrupo ArgentinoNational cohortDisease manifestationsSkeletal manifestationsGaucher diseaseSkeletal diseaseLarge burdenDiseaseSkeletal phenotypePhenotype correlationComplex allelesArgentine groupCollaborative studyManifestationsChildhoodCollaborative groupsGroupHigh frequencyCohortDIAPH1 Variants in Non–East Asian Patients With Sporadic Moyamoya Disease
Kundishora AJ, Peters ST, Pinard A, Duran D, Panchagnula S, Barak T, Miyagishima DF, Dong W, Smith H, Ocken J, Dunbar A, Nelson-Williams C, Haider S, Walker RL, Li B, Zhao H, Thumkeo D, Marlier A, Duy PQ, Diab NS, Reeves BC, Robert SM, Sujijantarat N, Stratman AN, Chen YH, Zhao S, Roszko I, Lu Q, Zhang B, Mane S, Castaldi C, López-Giráldez F, Knight JR, Bamshad MJ, Nickerson DA, Geschwind DH, Chen SL, Storm PB, Diluna ML, Matouk CC, Orbach DB, Alper SL, Smith ER, Lifton RP, Gunel M, Milewicz DM, Jin SC, Kahle KT. DIAPH1 Variants in Non–East Asian Patients With Sporadic Moyamoya Disease. JAMA Neurology 2021, 78: 993-1003. PMID: 34125151, PMCID: PMC8204259, DOI: 10.1001/jamaneurol.2021.1681.Peer-Reviewed Original ResearchConceptsSporadic moyamoya diseaseMoyamoya diseaseValidation cohortDiscovery cohortIntracranial internal carotid arteryRisk genesBilateral moyamoya diseaseTransfusion-dependent thrombocytopeniaLarger validation cohortNon-East Asian patientsInternal carotid arteryAsian individualsCompound heterozygous variantsNon-East AsiansProgressive vasculopathyTransmitted variantsAsian patientsChildhood strokeMedical recordsCarotid arteryTherapeutic ramificationsMAIN OUTCOMEMouse brain tissuePatientsUS hospitalsGenetics of agenesis/hypoplasia of the uterus and vagina: narrowing down the number of candidate genes for Mayer–Rokitansky–Küster–Hauser Syndrome
Mikhael S, Dugar S, Morton M, Chorich LP, Tam KB, Lossie AC, Kim HG, Knight J, Taylor HS, Mukherjee S, Capra JA, Phillips JA, Friez M, Layman LC. Genetics of agenesis/hypoplasia of the uterus and vagina: narrowing down the number of candidate genes for Mayer–Rokitansky–Küster–Hauser Syndrome. Human Genetics 2021, 140: 667-680. PMID: 33469725, PMCID: PMC9211441, DOI: 10.1007/s00439-020-02239-y.Peer-Reviewed Original ResearchConceptsKüster-Hauser syndromeMouse modelHuman studiesCandidate variantsAgenesis/hypoplasiaMethodsWhole-exome sequencingMayer-RokitanskyCandidate genesCongenital absenceExome sequencingAuditory defectsSanger sequencingPatientsRare variantsSyndromeUterusMRKHVaginaFurther investigationDigenic combinationsPhysiological candidatesGenetic basisSame geneVariant analysisGenes
2020
Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
Jin SC, Lewis SA, Bakhtiari S, Zeng X, Sierant MC, Shetty S, Nordlie SM, Elie A, Corbett MA, Norton BY, van Eyk CL, Haider S, Guida BS, Magee H, Liu J, Pastore S, Vincent JB, Brunstrom-Hernandez J, Papavasileiou A, Fahey MC, Berry JG, Harper K, Zhou C, Zhang J, Li B, Zhao H, Heim J, Webber DL, Frank MSB, Xia L, Xu Y, Zhu D, Zhang B, Sheth AH, Knight JR, Castaldi C, Tikhonova IR, López-Giráldez F, Keren B, Whalen S, Buratti J, Doummar D, Cho M, Retterer K, Millan F, Wang Y, Waugh JL, Rodan L, Cohen JS, Fatemi A, Lin AE, Phillips JP, Feyma T, MacLennan SC, Vaughan S, Crompton KE, Reid SM, Reddihough DS, Shang Q, Gao C, Novak I, Badawi N, Wilson YA, McIntyre SJ, Mane SM, Wang X, Amor DJ, Zarnescu DC, Lu Q, Xing Q, Zhu C, Bilguvar K, Padilla-Lopez S, Lifton RP, Gecz J, MacLennan AH, Kruer MC. Mutations disrupting neuritogenesis genes confer risk for cerebral palsy. Nature Genetics 2020, 52: 1046-1056. PMID: 32989326, PMCID: PMC9148538, DOI: 10.1038/s41588-020-0695-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCerebral PalsyCyclin DCytoskeletonDrosophilaExomeExome SequencingExtracellular MatrixF-Box ProteinsFemaleFocal AdhesionsGenetic Predisposition to DiseaseGenome, HumanHumansMaleMutationNeuritesRhoB GTP-Binding ProteinRisk FactorsSequence Analysis, DNASignal TransductionTubulinTumor Suppressor ProteinsConceptsDamaging de novo mutationsCerebral palsyDe novo mutationsCerebral palsy casesRisk genesDamaging de novoNovo mutationsWhole-exome sequencingPalsy casesNeuromotor functionD levelsMonogenic etiologyCyclin D levelsNeuronal connectivityPalsyGene confer riskConfer riskRecessive variantsNeurodevelopmental disorder genesReverse genetic screenDisorder genesParent-offspring triosGenome-wide significanceGenomic factorsCytoskeleton pathwayHERV1-env dependent unfolded protein response activation is a potential initiator of autoreactivity in autoimmune liver disease
Ekong U, Yao J, Knight J, Mehta S, Avitzur Y, Martinez M, Lobritto S, Mason A. HERV1-env dependent unfolded protein response activation is a potential initiator of autoreactivity in autoimmune liver disease. The Journal Of Immunology 2020, 204: 224.7-224.7. DOI: 10.4049/jimmunol.204.supp.224.7.Peer-Reviewed Original ResearchThe omentum of obese girls harbors small adipocytes and browning transcripts
Tarabra E, Nouws J, Vash-Margita A, Nadzam GS, Goldberg-Gell R, Van Name M, Pierpont B, Knight J, Shulman GI, Caprio S. The omentum of obese girls harbors small adipocytes and browning transcripts. JCI Insight 2020, 5 PMID: 32125283, PMCID: PMC7213797, DOI: 10.1172/jci.insight.135448.Peer-Reviewed Original ResearchConceptsSubcutaneous adipose tissueSAT depotsSleeve gastrectomySevere obesityInsulin resistanceInsulin sensitivitySmall adipocytesAdipose tissueAbdominal subcutaneous adipose tissueWeight lossType 2 diabetesOmental adipose tissueSubgroup of subjectsTranscriptomic profilesSAT biopsiesAdipocyte sizeObese girlsCardiovascular disease
2019
The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants.
Theisen JG, Sundaram V, Filchak MS, Chorich LP, Sullivan ME, Knight J, Kim HG, Layman LC. The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants. Scientific Reports 2019, 9: 20099. PMID: 31882810, PMCID: PMC6934803, DOI: 10.1038/s41598-019-53500-y.Peer-Reviewed Original Research