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. New England Journal Of Medicine 2023, 388: 1055-1056. PMID: 36920765, PMCID: PMC10134047, DOI: 10.1056/nejmc2211539.Peer-Reviewed Original Research
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 inhibitionIdentification of rare genetic variants in the PCDH genetic family in a cohort of transgender women
Theisen J, Chorich L, Xu H, Knight J, Kim H, Layman L. Identification of rare genetic variants in the PCDH genetic family in a cohort of transgender women. F&S Science 2024, 5: 283-292. PMID: 38942387, DOI: 10.1016/j.xfss.2024.06.005.Peer-Reviewed Original ResearchConceptsIdentification of rare genetic variantsRare genetic variantsDatabase for AnnotationGenetic variantsExome sequencingSanger sequencingTransgender womenCisgender menPlasma membrane adhesion moleculesGenetic familiesFunctional classification analysisGene family membersIntegrated Discovery toolMembrane adhesion moleculesVariant confirmationPcdh genesGene familyPcdhRare variantsGene variantsDiscovery analysisExomeSequenceSangerGenesImproved Survival With Adjuvant Cyclooxygenase 2 Inhibition in PIK3CA-Activated Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance)
Nowak J, Twombly T, Ma C, Shi Q, Haruki K, Fujiyoshi K, Väyrynen J, Zhao M, Knight J, Mane S, Shergill A, Kumar P, Couture F, Kuebler P, Krishnamurthi S, Tan B, Philip P, O'Reilly E, Shields A, Ogino S, Fuchs C, Meyerhardt J. Improved Survival With Adjuvant Cyclooxygenase 2 Inhibition in PIK3CA-Activated Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance). Journal Of Clinical Oncology 2024, 42: 2853-2859. PMID: 38889377, PMCID: PMC11392453, DOI: 10.1200/jco.23.01680.Peer-Reviewed Original ResearchDisease-free survivalStage III colon cancerIII colon cancerRisk of recurrenceGain-of-function mutationsColon cancerWildtype patientsMutation statusImproved survivalUsage of COX-2 inhibitorsGain-of-functionStandard adjuvant chemotherapyCOX-2Primary end pointCyclooxygenase 2 inhibitionCOX-2 inhibitorsColorectal cancer diagnosisCOX-2 inhibitionWhole-exome sequencing dataNational Cancer InstitutePIK3CA statusOverall survivalAdjuvant chemotherapyStatistically significant improvementClinical trial updateHeterozygous 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 ResearchLow-frequency inherited complement receptor variants are associated with purpura fulminans
Bendapudi P, Nazeen S, Ryu J, Söylemez O, Robbins A, Rouaisnel B, O'Neil J, 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 W, Hudspeth J, Pozdnyakova O, Nardi V, Knight J, Maas R, Sunyaev S, Losman J. Low-frequency inherited complement receptor variants are associated with purpura fulminans. Blood 2024, 143: 1032-1044. PMID: 38096369, PMCID: PMC10950473, DOI: 10.1182/blood.2023021231.Peer-Reviewed Original ResearchConceptsPurpura fulminansGermline whole-exome sequencingFunction-altering variantsInvestigate genetic risk factorsAssociated with purpura fulminansMultivariate logistic regression analysisWhole-exome sequencingInfectious purpura fulminansAssociated with PFCases of PFPatient sample collectionLogistic regression analysisBurden testsGenetic risk factorsFunctional characterizationSevere sepsisComplement receptor CR3Sepsis-inducedDisease phenotypeReceptor variantsDisease acuityRisk factorsMedical recordsLimited statistical powerInherited defects