Featured Publications
Attribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes
Cannataro VL, Mandell JD, Townsend JP. Attribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes. Molecular Biology And Evolution 2022, 39: msac084. PMID: 35580068, PMCID: PMC9113445, DOI: 10.1093/molbev/msac084.Peer-Reviewed Original ResearchConceptsBurden of cancerPublic health strategiesWhole-exome sequencingTobacco exposureLung cancerProstate adenocarcinomaBreast cancerCancer effectsHealth strategiesOncogenic driversCancer originCancer typesCancer cell lineagesCancerPathogen exposureExogenous mutational processesMajority of mutationsTumorsSingle nucleotide variantsPreventable processActivity accountsSurvivalOncogenic variantsCell lineagesProliferationEnvironmental and sex-specific molecular signatures of glioma causation
Claus EB, Cannataro VL, Gaffney SG, Townsend JP. Environmental and sex-specific molecular signatures of glioma causation. Neuro-Oncology 2021, 24: 29-36. PMID: 33942853, PMCID: PMC8730771, DOI: 10.1093/neuonc/noab103.Peer-Reviewed Original ResearchConceptsIDH wild-type tumorsWild-type tumorsEnvironmental risk factorsIDH-mutant tumorsRisk factorsCases of gliomaMolecular signaturesPIK3CA mutationsPossible risk exposuresMutation subtypesCancer effectsExogenous exposureAdult gliomasTumorsWhole-exome sequencing dataGliomasKinase domainMutational signaturesCancer-causing mutationsMalesFemalesNon-coding regionsPIK3R1SexCancer mutational signatures
2019
Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma
Lu L, Gaffney SG, Cannataro VL, Townsend J. Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma. Oral Oncology 2019, 101: 104554. PMID: 31887619, PMCID: PMC7273869, DOI: 10.1016/j.oraloncology.2019.104554.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkersFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateLymphocyte ActivationMaleMethyltransferasesMiddle AgedNeoplasm GradingNeoplasm StagingPrognosisProportional Hazards ModelsSquamous Cell Carcinoma of Head and NeckT-LymphocytesYoung AdultConceptsT cell activation scoreT cell activation statusAdjusted hazard ratioPatient survivalHPV statusHazard ratioActivation statusActivation scoresKaplan-Meier survival curvesImmune checkpoint blockadeCox regression modelNeck squamous carcinomaPotential therapeutic targetT cell activationHNSCC patientsSquamous carcinomaPatient mortalityLonger survivalExhaustion groupsTherapeutic targetSurvival curvesSignificant associationMRNA expressionPatientsSurvivalCombined 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 AssaysWagging the long tail of drivers of prostate cancer
Cannataro VL, Townsend JP. Wagging the long tail of drivers of prostate cancer. PLOS Genetics 2019, 15: e1007820. PMID: 30653503, PMCID: PMC6336235, DOI: 10.1371/journal.pgen.1007820.Commentaries, Editorials and Letters
2018
Potential 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 impactInfectionHeterogeneity 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
Radiation-Specific Clinical Data Should Be Included in Existing Large-Scale Genomic Datasets
Chen WS, Townsend JP, Yu JB. Radiation-Specific Clinical Data Should Be Included in Existing Large-Scale Genomic Datasets. International Journal Of Radiation Oncology • Biology • Physics 2017, 98: 8-10. PMID: 28587055, DOI: 10.1016/j.ijrobp.2017.01.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsWhole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up
Kadara H, Choi M, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Yoo Y, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Wistuba II, Herbst RS. Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up. Annals Of Oncology 2017, 28: 75-82. PMID: 27687306, PMCID: PMC5982809, DOI: 10.1093/annonc/mdw436.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalPoor recurrence-free survivalWhole-exome sequencingEarly-stage lung adenocarcinomaMutant lung adenocarcinomaLung adenocarcinomaImmune markersClinical outcomesExact testNatural killer cell infiltrationProportional hazards regression modelsGranzyme B levelsImmune marker analysisImmune profiling analysisPD-L1 expressionImmune-based therapiesTumoral PD-L1Hazards regression modelsKRAS mutant tumorsNormal lung tissuesMajority of deathsFisher's exact testHigh mutation burdenAnalysis of immunophenotypeRelevant molecular markers
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-thirdQuantifying Transmission of Clostridium difficile within and outside Healthcare Settings - Volume 22, Number 4—April 2016 - Emerging Infectious Diseases journal - CDC
Durham DP, Olsen MA, Dubberke ER, Galvani AP, Townsend JP. Quantifying Transmission of Clostridium difficile within and outside Healthcare Settings - Volume 22, Number 4—April 2016 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases 2016, 22: 608-616. PMID: 26982504, PMCID: PMC4806959, DOI: 10.3201/eid2204.150455.Peer-Reviewed Original ResearchConceptsClostridium difficile infectionAsymptomatic carriersLong-term care facility settingLong-term care facility residentsHospital-onset Clostridium difficile infectionCare facility residentsEffect of hospitalCommunity-based transmissionCommunity sourcesAsymptomatic patientsCDI incidenceDifficile infectionFacility residentsPatientsControl interventionsDifficile prevalenceC. difficileClostridium difficileHealthcare settingsNational databaseQuantifying transmissionTransmission routesHospitalDifficileControl measuresEarly and multiple origins of metastatic lineages within primary tumors
Zhao ZM, Zhao B, Bai Y, Iamarino A, Gaffney SG, Schlessinger J, Lifton RP, Rimm DL, Townsend JP. Early and multiple origins of metastatic lineages within primary tumors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 2140-2145. PMID: 26858460, PMCID: PMC4776530, DOI: 10.1073/pnas.1525677113.Peer-Reviewed Original ResearchConceptsMetastatic lineagesGenetic changesEarly genetic divergenceMolecular evolutionary modelsSingle genetic changeDivergent lineagesTumor phylogeneticsDivergence timesAncestral stateGenetic divergenceCancer lineagesPhylogenetic analysisEvolutionary processesLineagesCancer evolutionMultiple originsDriver genesCancer biologyCancer progressionSomatic mutationsTumor developmentEvolutionary modelsDriver mutationsChronogramMutations
2015
The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States
Durham DP, Skrip LA, Bruce RD, Vilarinho S, Elbasha EH, Galvani AP, Townsend JP. The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States. Clinical Infectious Diseases 2015, 62: 298-304. PMID: 26628566, PMCID: PMC4706637, DOI: 10.1093/cid/civ894.Peer-Reviewed Original ResearchConceptsHepatitis C virusInterferon-free DAAsHCV incidenceTreatment ratesChronic hepatitis C virusCases of cirrhosisInjection drug useImpact of administrationAnnual treatment ratesEnhanced screeningHCV prevalenceHCV screeningDecompensated cirrhosisHCV infectionHCV transmissionHepatitis CLiver transplantActing antiviralsLevels of screeningPatients 4C virusHepatocellular carcinomaEpidemiological dataUniversal screeningDrug useOptimizing age of cytomegalovirus screening and vaccination to avert congenital disease in the US
Alfaro-Murillo JA, Townsend JP, Galvani AP. Optimizing age of cytomegalovirus screening and vaccination to avert congenital disease in the US. Vaccine 2015, 34: 225-229. PMID: 26631416, DOI: 10.1016/j.vaccine.2015.11.039.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overChildChild, PreschoolCytomegalovirus InfectionsCytomegalovirus VaccinesDisease Transmission, InfectiousFemaleHumansImmunization ScheduleInfantInfant, NewbornInfectious Disease Transmission, VerticalMaleMass ScreeningMiddle AgedUnited StatesYoung AdultConceptsVaccine waningVaccine efficacyOptimal ageCMV vaccine candidatesLongitudinal clinical evaluationChild-bearing yearsYears of ageTransmission dynamicsCMV prevalenceCMV vaccinationCytomegalovirus ScreeningSeronegative femalesCongenital infectionCytomegalovirus infectionVaccine protectionSuch vaccinationClinical evaluationClinical trialsHearing lossVaccine candidatesVaccinationDemographic dataCongenital diseaseCognitive deficitsIndirect protectionImpact of bed capacity on spatiotemporal shifts in Ebola transmission
Townsend JP, Skrip LA, Galvani AP. Impact of bed capacity on spatiotemporal shifts in Ebola transmission. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 14125-14126. PMID: 26518509, PMCID: PMC4655579, DOI: 10.1073/pnas.1518484112.Commentaries, Editorials and Letters
2014
Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body
Talbert-Slagle K, Atkins KE, Yan KK, Khurana E, Gerstein M, Bradley EH, Berg D, Galvani AP, Townsend JP. Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body. PLOS Pathogens 2014, 10: e1004092. PMID: 24811311, PMCID: PMC4014458, DOI: 10.1371/journal.ppat.1004092.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2013
Epidemiological mechanisms of genetic resistance to kuru
Atkins KE, Townsend JP, Medlock J, Galvani AP. Epidemiological mechanisms of genetic resistance to kuru. Journal Of The Royal Society Interface 2013, 10: 20130331. PMID: 23740487, PMCID: PMC4043168, DOI: 10.1098/rsif.2013.0331.Peer-Reviewed Original ResearchConceptsTransmissible spongiform encephalopathiesGenotype frequency dataPopulation geneticsProtein geneGenetic resistanceEpidemiological mechanismsPrion protein geneMechanistic basisPrion proteinHost resistanceFatal neurodegenerative conditionHuman populationHuman resistancePapua New GuineaNew GuineaSpongiform encephalopathiesIncubation periodCodon 129Neurodegenerative conditionsIncidence dataReduced susceptibilityLong incubation periodKuruGenesMechanismPotential 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 dataOptimal targeting of seasonal influenza vaccination toward younger ages is robust to parameter uncertainty
Mbah M, Medlock J, Meyers LA, Galvani AP, Townsend JP. Optimal targeting of seasonal influenza vaccination toward younger ages is robust to parameter uncertainty. Vaccine 2013, 31: 3079-3089. PMID: 23684837, PMCID: PMC3764605, DOI: 10.1016/j.vaccine.2013.04.052.Peer-Reviewed Original ResearchConceptsOptimal vaccine allocationParameter uncertaintiesMathematical modelProbability distributionConsideration of uncertaintiesOutcome measuresVaccine allocationHuman population immunitySeasonal influenza vaccinationControl of influenzaUncertainty analysisFace of uncertaintyInfluenza vaccinationVaccine efficacySeasonal influenzaPopulation immunityUncertaintyEpidemiological dataHigh riskYounger ageYoung adultsEpidemiological parametersOptimal agePrevious recommendationsVaccineCost-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