James Knight, PhD
Research Scientist in GeneticsCards
About
Research
Publications
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. The New England Journal Of Medicine 2023, 388: 1055-1056. PMID: 36920765, PMCID: PMC10134047, DOI: 10.1056/nejmc2211539.Peer-Reviewed Original Research
2025
Pathogenic variants in medically actionable genes among women with Mayer-Rokitansky-Küster-Hauser syndrome
Theisen J, Chorich L, Hawkins Z, Xu H, Knight J, Kim H, Taylor H, Layman L. Pathogenic variants in medically actionable genes among women with Mayer-Rokitansky-Küster-Hauser syndrome. BMJ Connections Clinical Genetics And Genomics 2025, 2: e000004. DOI: 10.1136/bmjccgg-2024-000004.Peer-Reviewed Original ResearchMayer-Rokitansky-Kuster-HauserP/LP variantsUK BiobankAmerican CollegeElectronic medical recordsActionable genesMayer-Rokitansky-Kuster-Hauser syndromeExome sequencingGenetic counselingPrevalence of variantsMedical recordsMedical surveillanceSecondary findingsEmergency databaseStudy aimCongenital absenceUnexplained infertilityPathogenic variantsPrevalenceWomenBiobankSanger sequencingVariant prevalenceControl databaseAuditory anomaliesSUN-155 The Prevalence of Pathogenic Variants in Medically Actionable Genes Among Women with Idiopathic Hypogonadotropic Hypogonadism/Kallmann Syndrome
Kwal J, Chorich L, Hawkins Z, Grater L, Knight J, Taylor H, Layman L. SUN-155 The Prevalence of Pathogenic Variants in Medically Actionable Genes Among Women with Idiopathic Hypogonadotropic Hypogonadism/Kallmann Syndrome. Journal Of The Endocrine Society 2025, 9: bvaf149.2087. PMCID: PMC12545495, DOI: 10.1210/jendso/bvaf149.2087.Peer-Reviewed Original ResearchIdiopathic hypogonadotropic hypogonadismP/LP variantsMedical illnessActionable genesExome sequencingPrevalence of pathogenic variantsAction of gonadotropin-releasing hormoneInborn errorsSerum concentrations of luteinizing hormoneGnRH neuronal migrationFollicle-stimulating hormoneConcentrations of luteinizing hormoneInborn errors of metabolismGonadotropin-releasing hormoneCancer-related genesErrors of metabolismSecondary findingsHypogonadotropic hypogonadismOlfactory axonsIHH/KSLuteinizing hormonePathogenic variantsP/LPEndocrine disordersRisk factorsLZTR1 is a melanoma oncogene that promotes invasion and suppresses apoptosis
Bacchiocchi A, Mak M, Khan Z, Gong X, Sznol M, Na Z, Su H, Chan L, Yan Q, Zhao D, Mortlock R, Knight J, Slavoff S, Halaban R. LZTR1 is a melanoma oncogene that promotes invasion and suppresses apoptosis. Oncogene 2025, 44: 3974-3984. PMID: 40885854, PMCID: PMC12500468, DOI: 10.1038/s41388-025-03538-2.Peer-Reviewed Original ResearchDegradation of ubiquitinated proteinsActin-related proteinsActin cytoskeleton organizationUbiquitin-proteasome systemSrc tyrosine kinaseAnchorage-independent growthNormal cell survivalCargo adapterActin organizationProximity biotinylationCytoskeleton organizationLC-MS/MS proteomicsLeucine zipperProteasome systemUbiquitinated proteinsCo-ImmunoprecipitationTargeting Pyk2Cell spreadingMelanoma cellsEnvironmental stressGrowth advantageMolecular characterizationCell migrationCell survivalLZTR1Activation of Pvt1b isoform contributes to local Pvt1 abundance to repress Myc during stress
Li Q, Olivero C, Floyd E, Ding J, Dangelmaier E, Knight J, Dimitrova N. Activation of Pvt1b isoform contributes to local Pvt1 abundance to repress Myc during stress. PLOS Genetics 2025, 21: e1011790. PMID: 40743223, PMCID: PMC12312954, DOI: 10.1371/journal.pgen.1011790.Peer-Reviewed Original ResearchConceptsTranscription start siteSequence elementsOncogenic stressLong-read sequencingP53-induced increaseIsoform-specific activitiesMYC proto-oncogeneLncRNA lociStart siteMYC regulationMyc repressionLong noncoding RNAsStress responseMYCTumor suppressionNoncoding RNAsProto-oncogeneIsoformsTranscriptionAbundanceIn vivoIn vitro modelLociPVT1RepressionCopy Number Variants of Uncertain Significance by Chromosome Microarray Analysis from Consecutive Pediatric Patients: Reevaluation Following Current Guidelines and Reanalysis by Genome Sequencing
Li W, Xie X, Chai H, DiAdamo A, Bistline E, Li P, Dai Y, Knight J, Avni-Singer A, Burger J, Ment L, Spencer-Manzon M, Zhang H, Wen J. Copy Number Variants of Uncertain Significance by Chromosome Microarray Analysis from Consecutive Pediatric Patients: Reevaluation Following Current Guidelines and Reanalysis by Genome Sequencing. Genes 2025, 16: 874. PMID: 40869922, PMCID: PMC12385847, DOI: 10.3390/genes16080874.Peer-Reviewed Original ResearchConceptsWhole-genome sequencingChromosomal microarray analysisCopy number variantsGenome sequenceMicroarray analysisCausative genetic variantsDiagnostic valueClinical cytogenetics laboratoryPediatric casesConsecutive pediatric casesConsecutive pediatric patientsPathogenic CNVsGenetic variantsBenign CNVsGenetic counselorsClinical geneticistsRate of reclassificationLaboratory reevaluationCytogenetic laboratoriesPediatric patientsChromosomeClinical impactSequenceVariantsCopyAuto-sumoylation of the yeast Ubc9 E2 SUMO-conjugating enzyme extends cellular lifespan
Jeong D, Lee D, Kim S, Jeoung S, Zhao D, Knight J, Lam T, Jin J, Lee H, Hochstrasser M, Ryu H. Auto-sumoylation of the yeast Ubc9 E2 SUMO-conjugating enzyme extends cellular lifespan. Nature Communications 2025, 16: 3735. PMID: 40254622, PMCID: PMC12009981, DOI: 10.1038/s41467-025-58925-w.Peer-Reviewed Original ResearchConceptsE2 SUMO-conjugating enzymeSUMO-conjugating enzymeSUMO-specific proteasesPost-translational levelIn vitro evolutionSevere cellular stressCalorie restrictionRegulation of multiple targetsGene expression profilesIncreased mitochondrial activityCellular lifespanLifespan extensionReplicative lifespanCellular stressMitochondrial activityYeastCR-mediated lifespan extensionEnhanced growth rateEnzyme resultsDiverse processesExpression profilesLifespan effectsReplication abilityEnergy metabolismAged cells
2024
Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer
Robles-Oteíza C, Hastings K, Choi J, Sirois I, Ravi A, Expósito F, de Miguel F, Knight J, López-Giráldez F, Choi H, Socci N, Merghoub T, Awad M, Getz G, Gainor J, Hellmann M, Caron É, Kaech S, Politi K. Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer. Journal Of Experimental Medicine 2024, 222: e20231106. PMID: 39585348, PMCID: PMC11602551, DOI: 10.1084/jem.20231106.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsNon-small cell lung cancerAcquired ResistanceCheckpoint inhibitorsResistant tumorsPatients treated with anti-PD-1/PD-L1 therapyAnti-PD-1/PD-L1 therapyLung cancerResistance to immune checkpoint inhibitorsAssociated with decreased progression-free survivalHypoxia activated pro-drugsTargeting hypoxic tumor regionsTreat non-small cell lung cancerAnti-CTLA-4Anti-PD-1Immune checkpoint inhibitionTumor metabolic featuresProgression-free survivalCell lung cancerResistant cancer cellsHypoxic tumor regionsMHC-II levelsRegions of hypoxiaKnock-outCheckpoint inhibition