2022
Placing human gene families into their evolutionary context
Dornburg A, Mallik R, Wang Z, Bernal M, Thompson B, Bruford E, Nebert D, Vasiliou V, Yohe L, Yoder J, Townsend J. Placing human gene families into their evolutionary context. Human Genomics 2022, 16: 56. PMID: 36369063, PMCID: PMC9652883, DOI: 10.1186/s40246-022-00429-5.Peer-Reviewed Original ResearchConceptsHuman gene familyGene familyHuman genomeEvolutionary contextGene family evolutionNon-model organismsFirst human genomeGenome biologyComparative genomicsFamily evolutionDistant speciesDraft sequenceGenomic studiesGene expressionGenome sequencingSequence complexityGenomeCancer biologyUnprecedented insightsNovel discoveriesCritical roleOrganismsBiologyComparative approachFamily
2021
Mechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy
Wells CR, Cao Y, Durham DP, Byrareddy SN, Ansari AA, Ruddle NH, Townsend JP, Galvani AP, Perelson AS. Mechanistic basis of post-treatment control of SIV after anti-α4β7 antibody therapy. PLOS Computational Biology 2021, 17: e1009031. PMID: 34106916, PMCID: PMC8189501, DOI: 10.1371/journal.pcbi.1009031.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyViral loadPost-treatment controlAnti-α4β7 antibodyViral remissionAntibody treatmentViral controlCombinations of cARTImmune effector cell responsesPost-treatment viral controlSIV RNA copies/Depletion of CD8Ongoing immune responseEarly SIV infectionRNA copies/Stable viral loadEffector cell responsesViral load dataDifferent viral loadsAbsence of treatmentSubset of animalsNonhuman primate experimentsDifferent primary mechanismsLongitudinal viral load dataCART cessation
2020
Comparative Genomics within and across Bilaterians Illuminates the Evolutionary History of ALK and LTK Proto-Oncogene Origination and Diversification
Dornburg A, Wang Z, Wang J, Mo ES, López-Giráldez F, Townsend JP. Comparative Genomics within and across Bilaterians Illuminates the Evolutionary History of ALK and LTK Proto-Oncogene Origination and Diversification. Genome Biology And Evolution 2020, 13: evaa228. PMID: 33196781, PMCID: PMC7851593, DOI: 10.1093/gbe/evaa228.Peer-Reviewed Original ResearchConceptsLeukocyte tyrosine kinaseEvolutionary historyPhylogenetic analysisProtein-coding genesComparative genomic analysisEarly embryonic expressionMetazoan genomesComparative genomicsPhylogenetic contextModel organismsEmbryonic expressionModel speciesHuman genesKey genesGenomic analysisImportant genesMammal systemsFunctional convergenceTyrosine kinaseMolecular homologyGenesFunctional roleVertebratesMammal modelsHomologyDogs and pigs are transport hosts of Necator americanus: Molecular evidence for a zoonotic mechanism of human hookworm transmission in Ghana
Boyko RH, Harrison L, Humphries D, Galvani AP, Townsend JP, Otchere J, Wilson MD, Cappello M. Dogs and pigs are transport hosts of Necator americanus: Molecular evidence for a zoonotic mechanism of human hookworm transmission in Ghana. Zoonoses And Public Health 2020, 67: 474-483. PMID: 32529782, DOI: 10.1111/zph.12708.Peer-Reviewed Original ResearchConceptsPig fecal samplesProspective molecular studyNematode Toxocara canisPig ownershipPig samplesNematode larvaeAnimal faecesTransport hostsDog ownershipKintampo NorthFecal samplesToxocara canisProxy of exposureHuman infectionsPigsHookworm eggsSubsequent prospective studyHookworm transmissionDogsResource-limited countriesFaecesPCR analysisGhanaMolecular evidenceSignificant morbidity
2019
Combined Aurora Kinase A (AURKA) and WEE1 Inhibition Demonstrates Synergistic Antitumor Effect in Squamous Cell Carcinoma of the Head and Neck
Lee JW, Parameswaran J, Sandoval-Schaefer T, Eoh KJ, Yang DH, Zhu F, Mehra R, Sharma R, Gaffney SG, Perry EB, Townsend JP, Serebriiskii IG, Golemis EA, Issaeva N, Yarbrough WG, Koo JS, Burtness B. Combined Aurora Kinase A (AURKA) and WEE1 Inhibition Demonstrates Synergistic Antitumor Effect in Squamous Cell Carcinoma of the Head and Neck. Clinical Cancer Research 2019, 25: 3430-3442. PMID: 30755439, PMCID: PMC6548643, DOI: 10.1158/1078-0432.ccr-18-0440.Peer-Reviewed Original ResearchAnimalsAntineoplastic AgentsApoptosisAurora Kinase ACell Cycle ProteinsCell Line, TumorDisease Models, AnimalDrug SynergismFemaleFluorescent Antibody TechniqueGene ExpressionHumansMaleMiceNeoplasm GradingNeoplasm StagingProtein Kinase InhibitorsProtein-Tyrosine KinasesSquamous Cell Carcinoma of Head and NeckXenograft Model Antitumor Assays
2018
Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel
Santos LA, Adhikarla H, Yan X, Wang Z, Fouts DE, Vinetz JM, Alcantara LCJ, Hartskeerl RA, Goris MGA, Picardeau M, Reis MG, Townsend JP, Zhao H, Ko AI, Wunder EA. Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel. Frontiers In Cellular And Infection Microbiology 2018, 8: 193. PMID: 29971217, PMCID: PMC6018220, DOI: 10.3389/fcimb.2018.00193.Peer-Reviewed Original ResearchConceptsSerovar CopenhageniPublic health relevanceSevere casesSerogroup IcterohaemorrhagiaeSerovar IcterohaemorrhagiaeWorldwide zoonosisHealth relevanceIcterohaemorrhagiaeCopenhageniVirulent strainHigh discriminatory powerSerovarsGlobal isolatesFrameshift mutationDiscriminatory powerFirst studyPathogenic speciesIsolatesPotential effectiveness of long-acting injectable pre-exposure prophylaxis for HIV prevention in men who have sex with men: a modelling study
Marshall BDL, Goedel WC, King MRF, Singleton A, Durham DP, Chan PA, Townsend JP, Galvani AP. Potential effectiveness of long-acting injectable pre-exposure prophylaxis for HIV prevention in men who have sex with men: a modelling study. The Lancet HIV 2018, 5: e498-e505. PMID: 29908917, PMCID: PMC6138558, DOI: 10.1016/s2352-3018(18)30097-3.Peer-Reviewed Original ResearchConceptsNew HIV infectionsInjectable PrEPPre-exposure prophylaxisOral PrEPHIV infectionHIV transmissionInjectable pre-exposure prophylaxisOral pre-exposure prophylaxisAbsence of PrEPDaily oral PrEPTime-varying efficacyPhase 3 trialRetention of patientsNational InstituteDiscontinuation ratesSafety trialMacaque modelHIV preventionCumulative numberClinical carePharmacokinetic dataCoverage levelsPotential effectivenessPopulation-level impactInfectionNeutral Theory and the Somatic Evolution of Cancer
Cannataro VL, Townsend JP. Neutral Theory and the Somatic Evolution of Cancer. Molecular Biology And Evolution 2018, 35: 1308-1315. PMID: 29684198, PMCID: PMC5967571, DOI: 10.1093/molbev/msy079.Peer-Reviewed Original ResearchHeterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C
Cannataro VL, Gaffney SG, Stender C, Zhao ZM, Philips M, Greenstein AE, Townsend JP. Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C. Oncogene 2018, 37: 2444-2455. PMID: 29453361, DOI: 10.1038/s41388-017-0105-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SubstitutionAnimalsCase-Control StudiesDisease ProgressionDrug Resistance, NeoplasmFemaleGenetic HeterogeneityHigh-Throughput Nucleotide SequencingHumansMaleMiceMice, Inbred BALB CMice, NudeNeoplasmsOncogenesPoint MutationPolymorphism, Single NucleotideProto-Oncogene Proteins p21(ras)Sequence Analysis, DNAYoung AdultConceptsTime of treatmentTargeted therapyLung tumorsDe novo mutationsNew targeted therapiesPatient-derived xenograftsHighest fitness advantageKRAS G12C variantNovo mutationsEvidence of heterogeneityNovel KRAS mutationPreclinical promiseSuch therapyHigh prevalenceKRAS mutationsTreatment resistanceBRAF V600EKRASTherapyTargeted inhibitorsTumorsAssociated oncogeneRAS genesHuman cancersOncogenic mutations
2017
Detection of Regional Variation in Selection Intensity within Protein-Coding Genes Using DNA Sequence Polymorphism and Divergence
Zhao ZM, Campbell MC, Li N, Lee DSW, Zhang Z, Townsend JP. Detection of Regional Variation in Selection Intensity within Protein-Coding Genes Using DNA Sequence Polymorphism and Divergence. Molecular Biology And Evolution 2017, 34: 3006-3022. PMID: 28962009, PMCID: PMC5850860, DOI: 10.1093/molbev/msx213.Peer-Reviewed Original ResearchConceptsPoisson random fieldRandom fieldsEnsemble of modelsRandom field frameworkField frameworkClustering modelHistorical demographic trendsAmino acid-altering substitutionsSelection intensityEnsembleHigh powerUniform selectionProtein-coding genesProtein coding genesHeterogeneity of selectionDNA sequence polymorphismsComparison of polymorphismsNew insights on the sister lineage of percomorph fishes with an anchored hybrid enrichment dataset
Dornburg A, Townsend JP, Brooks W, Spriggs E, Eytan RI, Moore JA, Wainwright PC, Lemmon A, Lemmon EM, Near TJ. New insights on the sister lineage of percomorph fishes with an anchored hybrid enrichment dataset. Molecular Phylogenetics And Evolution 2017, 110: 27-38. PMID: 28254474, DOI: 10.1016/j.ympev.2017.02.017.Peer-Reviewed Original Research
2016
One Health approach to cost-effective rabies control in India
Fitzpatrick MC, Shah HA, Pandey A, Bilinski AM, Kakkar M, Clark AD, Townsend JP, Abbas SS, Galvani AP. One Health approach to cost-effective rabies control in India. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 14574-14581. PMID: 27994161, PMCID: PMC5187709, DOI: 10.1073/pnas.1604975113.Peer-Reviewed Original ResearchConceptsHuman rabiesRabies deathsCanine vaccinationStray dogsHuman rabies deathsRabies controlCost-effectiveness thresholdPostexposure vaccinationWHO criteriaDog bitesAutopsy dataHealth outcomesHealth approachSurveillance dataVaccinationCost-effective strategyDogsRabiesRabies surveillance dataOne-thirdPhyloOncology: Understanding cancer through phylogenetic analysis
Somarelli JA, Ware KE, Kostadinov R, Robinson JM, Amri H, Abu-Asab M, Fourie N, Diogo R, Swofford D, Townsend JP. PhyloOncology: Understanding cancer through phylogenetic analysis. Biochimica Et Biophysica Acta (BBA) - Reviews On Cancer 2016, 1867: 101-108. PMID: 27810337, PMCID: PMC9583457, DOI: 10.1016/j.bbcan.2016.10.006.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdaptation, PhysiologicalAlgorithmsAnimalsBiomarkers, TumorCell Transformation, NeoplasticEvolution, MolecularGene Expression Regulation, NeoplasticGenetic FitnessGenetic Predisposition to DiseaseGenomicsHeredityHumansModels, GeneticMutationNeoplasmsPedigreePhenotypePhylogenySignal TransductionSystems BiologyTime FactorsConceptsDr. Robert A. GatenbyGenome-scale dataSystems biology approachPowerful systems biology approachUse of phylogeneticsPhylogenetic analysisBiology approachPhylogenetic applicationsSubclonal evolutionCancer biologyCancer progressionSuite of algorithmsPhylogeneticsCancer data setsCancer samplesImproved therapeutic interventionRobust approachDecades of researchFundamental insightsNew toolBiologyDiverse fieldsGatenbyData setsTherapeutic interventionsClimatic and evolutionary drivers of phase shifts in the plague epidemics of colonial India
Lewnard JA, Townsend JP. Climatic and evolutionary drivers of phase shifts in the plague epidemics of colonial India. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 14601-14608. PMID: 27791071, PMCID: PMC5187705, DOI: 10.1073/pnas.1604985113.Peer-Reviewed Original ResearchConceptsPlague resistanceEnvironmental driversIntense natural selectionWild host populationsIntense selective pressureEvolutionary driversPossible evolutionary basisHost evolutionNatural selectionDisease resistanceEvolutionary selectionFlea population dynamicsEvolutionary basisSelective pressureEvolutionary processesPopulation dynamicsHost populationsWildlife hostsLocal persistencePlague dynamicsCommensal ratsDisease agentsPowerful insightsDisease transmissionEcologyDeterminants of Human African Trypanosomiasis Elimination via Paratransgenesis
Gilbert JA, Medlock J, Townsend JP, Aksoy S, Mbah M, Galvani AP. Determinants of Human African Trypanosomiasis Elimination via Paratransgenesis. PLOS Neglected Tropical Diseases 2016, 10: e0004465. PMID: 26954675, PMCID: PMC4783105, DOI: 10.1371/journal.pntd.0004465.Peer-Reviewed Original Research
2015
A comprehensive phylogeny of birds (Aves) using targeted next-generation DNA sequencing
Prum RO, Berv JS, Dornburg A, Field DJ, Townsend JP, Lemmon EM, Lemmon AR. A comprehensive phylogeny of birds (Aves) using targeted next-generation DNA sequencing. Nature 2015, 526: 569-573. PMID: 26444237, DOI: 10.1038/nature15697.Peer-Reviewed Original Research
2014
Phylogenetic informativeness reconciles ray-finned fish molecular divergence times
Dornburg A, Townsend JP, Friedman M, Near TJ. Phylogenetic informativeness reconciles ray-finned fish molecular divergence times. BMC Ecology And Evolution 2014, 14: 169. PMID: 25103329, PMCID: PMC4236503, DOI: 10.1186/s12862-014-0169-0.Peer-Reviewed Original ResearchConceptsMolecular age estimatesMolecular divergence timesDivergence timesSequence dataMolecular divergence time estimationMitochondrial sequence dataPhylogenetic informativeness profilesDivergence time estimationRay-finned fishesTree of lifeMolecular clock methodsSubstitution rate heterogeneityMolecular clock modelBranch length estimatesPhylogenetic informativenessNuclear sequencesRecent divergenceMolecular clockIndividual genesPhylogenetic inferenceDNA sequence alignmentRate heterogeneityFossil recordSequence alignmentClock method
2013
Potential Cost-Effectiveness of Schistosomiasis Treatment for Reducing HIV Transmission in Africa – The Case of Zimbabwean Women
Mbah M, Poolman EM, Atkins KE, Orenstein EW, Meyers LA, Townsend JP, Galvani AP. Potential Cost-Effectiveness of Schistosomiasis Treatment for Reducing HIV Transmission in Africa – The Case of Zimbabwean Women. PLOS Neglected Tropical Diseases 2013, 7: e2346. PMID: 23936578, PMCID: PMC3731236, DOI: 10.1371/journal.pntd.0002346.Peer-Reviewed Original ResearchConceptsFemale genital schistosomiasisHIV infectionPraziquantel administrationHIV transmissionSchool-aged childrenAnnual administrationHIV prevalenceSchistosoma haematobiumCost-effective public health interventionsAntenatal clinic dataReducing HIV TransmissionBurden of HIVCases of HIVTen-year periodPublic health interventionsCost-effectiveness analysisNovel intervention strategiesGenital schistosomiasisGenital infectionSaharan AfricaCost-saving strategyNet savingsSchistosomiasis treatmentEpidemiological dataClinic dataEvaluating Phylogenetic Informativeness as a Predictor of Phylogenetic Signal for Metazoan, Fungal, and Mammalian Phylogenomic Data Sets
López-Giráldez F, Moeller AH, Townsend JP. Evaluating Phylogenetic Informativeness as a Predictor of Phylogenetic Signal for Metazoan, Fungal, and Mammalian Phylogenomic Data Sets. BioMed Research International 2013, 2013: 621604. PMID: 23878813, PMCID: PMC3708382, DOI: 10.1155/2013/621604.Peer-Reviewed Original ResearchConceptsPhylogenomic data setsPhylogenetic informativenessPhylogenetic signalEffects of homoplasyPoor phylogenetic resolutionPhylogenetic resolutionSister cladeOutgroup taxaPhylogenetic researchTaxonomic groupsPhylogenetic inferenceAdvantageous genesGenesMetazoansCladeTaxaDiverse groupDiverse time scalesHomoplasyHaphazard samplingMammalsFungiOrganismsFungalMarkersCost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa
Mbah M, Kjetland EF, Atkins KE, Poolman EM, Orenstein EW, Meyers LA, Townsend JP, Galvani AP. Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 7952-7957. PMID: 23589884, PMCID: PMC3651507, DOI: 10.1073/pnas.1221396110.Peer-Reviewed Original ResearchConceptsCommunity-based interventionsHIV infectionHIV transmissionSchistosoma haematobiumFemale genital schistosomiasisAdministration of praziquantelSaharan AfricaRural ZimbabweS. haematobium transmissionGenital schistosomiasisGenital infectionHealth payersSchool-aged childrenIntervention periodEpidemiological dataEpidemiological studiesS. haematobiumSchistosomiasis prevalenceHealth educationInfectionSchistosomiasisYoung womenHaematobiumInterventionHIV