2024
Epigenetic heterogeneity hotspots in human liver disease progression.
Hlady R, Zhao X, El Khoury L, Wagner R, Luna A, Pham K, Pyrosopoulos N, Jain D, Wang L, Liu C, Robertson K. Epigenetic heterogeneity hotspots in human liver disease progression. Hepatology 2024 PMID: 39028883, DOI: 10.1097/hep.0000000000001023.Peer-Reviewed Original ResearchEpigenetic heterogeneityGenome-wide profiling of DNA methylationProfiling of DNA methylationDNA methylation landscapeGenome-wide profilingGene expression heterogeneityCopy number variationsMethylation landscapeOnset of liver cancerDNA methylationLiver disease developmentPhenotypic effectsNumber variationsGenetic heterogeneityTranscriptional heterogeneityFunctional screeningLiver disease progressionCopy numberExpression heterogeneityGene expressionTumor suppressorHuman diseasesGenesPathological phenotypesKey pathwaysCombining genomic data and infection estimates to characterize the complex dynamics of SARS-CoV-2 Omicron variants in the US
Lopes R, Pham K, Klaassen F, Chitwood M, Hahn A, Redmond S, Swartwood N, Salomon J, Menzies N, Cohen T, Grubaugh N. Combining genomic data and infection estimates to characterize the complex dynamics of SARS-CoV-2 Omicron variants in the US. Cell Reports 2024, 43: 114451. PMID: 38970788, DOI: 10.1016/j.celrep.2024.114451.Peer-Reviewed Original Research
2022
Nicotine dose-dependent epigenomic-wide DNA methylation changes in the mice with long-term electronic cigarette exposure.
Peng G, Xi Y, Bellini C, Pham K, Zhuang ZW, Yan Q, Jia M, Wang G, Lu L, Tang MS, Zhao H, Wang H. Nicotine dose-dependent epigenomic-wide DNA methylation changes in the mice with long-term electronic cigarette exposure. American Journal Of Cancer Research 2022, 12: 3679-3692. PMID: 36119846, PMCID: PMC9442002.Peer-Reviewed Original ResearchElectronic cigarette exposureCigarette exposureMale ApoE-/- miceApoE-/- miceCytokine mRNA expressionPoor health outcomesWhite blood cellsElectronic cigarette useDose-dependent mannerE-cigarette aerosolAerosol inhalationCigarette smokingActivation of MAPKHigher nicotine concentrationsMAPK pathway activationCell-damaging effectsCpG sitesHealth outcomesCigarette useMRNA expressionNicotine concentrationsPathway activationSignificant CpG sitesBlood cellsSignificant alterationsSaliVISION: a rapid saliva-based COVID-19 screening and diagnostic test with high sensitivity and specificity
DeFina SM, Wang J, Yang L, Zhou H, Adams J, Cushing W, Tuohy B, Hui P, Liu C, Pham K. SaliVISION: a rapid saliva-based COVID-19 screening and diagnostic test with high sensitivity and specificity. Scientific Reports 2022, 12: 5729. PMID: 35388102, PMCID: PMC8986854, DOI: 10.1038/s41598-022-09718-4.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Diagnostic testingRespiratory syndrome coronavirus 2Reverse transcription loop-mediated isothermal amplificationTranscription loop-mediated isothermal amplificationTranscription-quantitative polymerase chain reactionSyndrome coronavirus 2COVID-19 diagnostic testingCoronavirus disease 2019Public health challengeRapid diagnostic testingCOVID-19 screeningQuantitative polymerase chain reactionLoop-mediated isothermal amplificationCoronavirus 2Polymerase chain reactionLaboratory testingRapid diagnostic assaysDisease 2019RT-LAMPInvasive sample collectionDiagnostic testsChain reactionRapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons
Chaguza C, Coppi A, Earnest R, Ferguson D, Kerantzas N, Warner F, Young HP, Breban MI, Billig K, Koch RT, Pham K, Kalinich CC, Ott IM, Fauver JR, Hahn AM, Tikhonova IR, Castaldi C, De Kumar B, Pettker CM, Warren JL, Weinberger DM, Landry ML, Peaper DR, Schulz W, Vogels CBF, Grubaugh ND. Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons. Med 2022, 3: 325-334.e4. PMID: 35399324, PMCID: PMC8983481, DOI: 10.1016/j.medj.2022.03.010.Peer-Reviewed Original ResearchConceptsSpike gene target failureSARS-CoV-2 Omicron variantPositivity rateOmicron variantOmicron infectionVaccine dosesVaccine-induced immunityNumber of dosesTest positivity rateOdds of infectionSARS-CoV-2Significant reductionDominant Delta variantUnvaccinated personsVaccination statusHigher oddsDelta variantInfectionVaccine manufacturersDisease controlVirus copiesDosesPCR testOddsTarget failureEmerging Trends in the Pathological Research of Human Papillomavirus-positive Oropharyngeal Squamous Cell Carcinoma
Crane J, Shi Q, Xi Y, Lai J, Pham K, Wang H. Emerging Trends in the Pathological Research of Human Papillomavirus-positive Oropharyngeal Squamous Cell Carcinoma. Journal Of Clinical And Translational Pathology 2022, 2: 31-36. PMID: 36275841, PMCID: PMC9585478, DOI: 10.14218/jctp.2022.00004.Peer-Reviewed Original ResearchOropharyngeal squamous cell carcinomaSquamous cell carcinomaCell carcinomaHuman papillomavirusHuman papillomavirus-positive oropharyngeal squamous cell carcinomaHPV-positive oropharyngeal squamous cell carcinomaHPV-negative oropharyngeal squamous cell carcinomaActive human papillomavirusNew targetsLong-term survivalPotential new targetsDefinitive treatmentHPV 16Treatment optionsSurvival prognosisTumor prognosisAdvanced stageHealth responsePrecision treatmentPrecision medicinePatientsCarcinomaPrognosisTreatmentPathological researchInterferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance
Hlady RA, Zhao X, Khoury L, Luna A, Pham K, Wu Q, Lee J, Pyrsopoulos NT, Liu C, Robertson KD. Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance. Hepatology 2022, 75: 983-996. PMID: 34387871, PMCID: PMC9416882, DOI: 10.1002/hep.32111.Peer-Reviewed Original ResearchConceptsDNA methylationHistone modificationsWide DNA methylationAberrant DNA methylationGene expression analysisDNA methyltransferase inhibitorOpen chromatinEpigenetic mechanismsEpigenetic targetsHuman patient samplesEpigenetic changesEpigenomeMethyltransferase inhibitorTargetable vulnerabilitiesMethylationHCC cell linesImmortalized hepatocytesCell linesFunctional effectsChronic HCV infectionChromatinHCV infectionImmune responsePatient samplesSynergizes
2021
Potential role of IFN-α in COVID-19 patients and its underlying treatment options
Yang L, Wang J, Hui P, Yarovinsky TO, Badeti S, Pham K, Liu C. Potential role of IFN-α in COVID-19 patients and its underlying treatment options. Applied Microbiology And Biotechnology 2021, 105: 4005-4015. PMID: 33950278, PMCID: PMC8096625, DOI: 10.1007/s00253-021-11319-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSARS-CoV-2 infectionIFN-α subtypesRespiratory virus diseasesCOVID-19 patientsImmunoregulatory effectsInflammatory responseSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2COVID-19 pathogenesisTreatment of patientsUncontrolled inflammatory responseSyndrome coronavirus 2Interferon-stimulated gene expressionPotential therapeutic strategySeverity of infectionSARS-CoV-2Virus diseaseInnate immune systemPossible side effectsCOVID-19 diseaseViral infection treatmentDrug candidatesCoronavirus 2Treatment optionsE-Cigarettes Promote Macrophage-Tumor Cells Crosstalk: Focus on Breast Carcinoma Progression and Lung Metastasis
Pham K, DeFina S, Wang H. E-Cigarettes Promote Macrophage-Tumor Cells Crosstalk: Focus on Breast Carcinoma Progression and Lung Metastasis. Exploratory Research And Hypothesis In Medicine 2021, 6: 60-66. PMID: 35419501, PMCID: PMC9005083, DOI: 10.14218/erhm.2021.00002.Peer-Reviewed Original ResearchTumor-associated macrophagesBreast cancerMetastasis of BCTumor microenvironmentC motif chemokine ligand 5Enhanced tumor malignancyRisk of metastasisConventional cigarette smokingAggressive breast cancerChemokine ligand 5Breast carcinoma progressionCig vapingDNA damaging effectsCigarette smokingLung metastasesImmune cellsAggressive phenotypeBC progressionMacrophage activationCig useMetastasisTumor malignancyCarcinoma progressionE-cigsE-cigarettes
2020
Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR9 (Toll-Like Receptor 9)-Mediated Atherosclerosis
Li J, Huynh L, Cornwell WD, Tang MS, Simborio H, Huang J, Kosmider B, Rogers TJ, Zhao H, Steinberg MB, Thu Thi Le L, Zhang L, Pham K, Liu C, Wang H. Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR9 (Toll-Like Receptor 9)-Mediated Atherosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2020, 41: 839-853. PMID: 33380174, PMCID: PMC8608030, DOI: 10.1161/atvbaha.120.315556.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisDisease Models, AnimalDNA DamageDNA, MitochondrialE-Cigarette VaporFemaleHumansInflammationInflammation MediatorsMacrophagesMaleMiceMice, Inbred C57BLMice, Knockout, ApoEMiddle AgedMitochondriaRAW 264.7 CellsSignal TransductionSmokersToll-Like Receptor 9VapingConceptsECV exposureTLR9 expressionInflammatory cytokinesClassical monocytesTLR9 activationAtherosclerotic plaquesEight-week-old ApoEUpregulation of TLR9Expression of TLR9Atherosclerotic lesion developmentOil Red O stainingToll-like receptorsDays/weekE-cig exposureMonocytes/macrophagesNormal laboratory dietRed O stainingPotential pharmacological targetElectronic cigarette useHours/dayProinflammatory cytokinesCig vaporPlasma levelsTLR9 antagonistTLR9 inhibitorE-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1
Pham K, Huynh D, Le L, Delitto D, Yang L, Huang J, Kang Y, Steinberg MB, Li J, Zhang L, Liu D, Tang MS, Liu C, Wang H. E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1. Cancer Letters 2020, 491: 132-145. PMID: 32829009, PMCID: PMC9703643, DOI: 10.1016/j.canlet.2020.08.010.Peer-Reviewed Original ResearchConceptsBC cell growthCig exposureLung metastasesBreast cancerVCAM-1V-CAM-1Role of CCL5Upregulated protein expressionBC cell survivalE-cig exposurePro-tumorigenic factorsBC cell apoptosisBreast carcinoma progressionMetastatic lung colonizationCCR5 axisMFP tumorsTAMs infiltrationInfiltrated macrophagesCell growthCo-culture systemImmunohistochemical stainsCell crosstalkBC cellsBC growthProliferation indexElectronic cigarettes promotes the lung colonization of human breast cancer in NOD-SCID-Gamma mice.
Huynh D, Huang J, Le LTT, Liu D, Liu C, Pham K, Wang H. Electronic cigarettes promotes the lung colonization of human breast cancer in NOD-SCID-Gamma mice. International Journal Of Clinical And Experimental Pathology 2020, 13: 2075-2081. PMID: 32922603, PMCID: PMC7476960.Peer-Reviewed Original ResearchE-cigsNOD-SCIDGamma miceTumor cellsCig vapour extractElectronic cigarette smokingHuman breast cancer cell line MDA-MB-231Breast cancer cell line MDA-MB-231Cancer cell line MDA-MB-231Human breast cancer cellsCell line MDA-MB-231E-cig exposureHuman breast cancerMetastasis-promoting effectsTail vein injectionBreast cancer cellsTumor cell proliferationMDA-MB-231Tumor cell apoptosisCig exposureCigarette smokingLung metastasesTumor loadTumor mortalityBreast cancerIdentification of small molecules by screening a mixture-based scaffold compound library for treatment of alpha-1 antitrypsin deficiency
Zhang X, Santos R, Debevec G, Li D, Schutte R, Pham K, Liu C, Ostrov DA, Giulianotti M. Identification of small molecules by screening a mixture-based scaffold compound library for treatment of alpha-1 antitrypsin deficiency. Biochemical And Biophysical Research Communications 2020, 527: 317-323. PMID: 32446387, DOI: 10.1016/j.bbrc.2020.04.037.Peer-Reviewed Original ResearchConceptsSmall moleculesCompound librariesStructural diversityActive compoundsPreliminary structure-activity relationshipScaffold libraryIndividual active compoundsStructure-activity relationshipsMixture librariesTitration experimentsCrystal structureMolecular dockingPolymerization sitePromising scaffoldCompoundsMixture formatMoleculesPosition R1Mixture samplesScaffoldsPotential binding sitesBinding sitesDockingThe role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC
Brown M, Zhang W, Yan D, Kenath R, Le L, Wang H, Delitto D, Ostrov D, Robertson K, Liu C, Pham K. The role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC. PLOS ONE 2020, 15: e0226917. PMID: 31929540, PMCID: PMC6957139, DOI: 10.1371/journal.pone.0226917.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTypes of cancerDuctal adenocarcinomaSurvivin expressionSurvivin inhibitorClinical response rateNovel survivin inhibitorHalf of patientsElevated survivin expressionLower patient survivalPancreatic tumor microenvironmentPotential therapeutic targetExpression of survivinRole of survivinField of oncologyPancreatic cancer linesImmunotherapeutic approachesPatient survivalUntreated cohortTherapeutic responseInhibitor of survivinTreatment resistancePDAC progressionEffective treatmentTumor cell migration
2019
A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo
Zhang X, Pham K, Li D, Schutte RJ, Gonzalo DH, Zhang P, Oshins R, Tan W, Brantly M, Liu C, Ostrov DA. A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo. Cells 2019, 8: 1586. PMID: 31817705, PMCID: PMC6953066, DOI: 10.3390/cells8121586.Peer-Reviewed Original ResearchConceptsLiver diseaseAssociated liver injuryChronic liver diseaseMutant alpha 1Common genetic causePiZ miceCurative therapyLiver injuryLiver fibrosisNovel small moleculesAnimal modelsAlpha 1Genetic causeDiseaseIntracellular accumulationAlphaCandidate compoundsHuman alphaMutant alphaCell modelAATDFibrosisInjuryTherapySmall moleculesEnhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination
Wu Q, Wang X, Pham K, Luna A, Studzinski GP, Liu C. Enhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination. The Journal Of Steroid Biochemistry And Molecular Biology 2019, 197: 105524. PMID: 31704246, PMCID: PMC7015782, DOI: 10.1016/j.jsbmb.2019.105524.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaVitamin DOral multi-kinase inhibitorTreatment of HCCAutophagy markers Beclin1Vitamin D insufficiencyCarnosic acidAdvanced hepatocellular carcinomaPromising therapeutic optionVitamin D analogsMulti-kinase inhibitorCell linesElevated protein levelsAnti-oxidant propertiesHCC cell linesHuman neoplastic cellsD insufficiencyGlobal cancer mortalityHepatocellular carcinoma cellsSystemic treatmentTherapeutic optionsCancer mortalityHCC cell deathPreclinical studiesLiver cancerTumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer
Sivaram N, McLaughlin PA, Han HV, Petrenko O, Jiang YP, Ballou LM, Pham K, Liu C, van der Velden A, Lin RZ. Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer. Journal Of Clinical Investigation 2019, 129: 3264-3276. PMID: 31112530, PMCID: PMC6668699, DOI: 10.1172/jci123540.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCell Line, TumorClass I Phosphatidylinositol 3-KinasesHistocompatibility Antigens Class IHumansLymphocytes, Tumor-InfiltratingMiceMice, KnockoutMice, SCIDNeoplasms, ExperimentalPancreatic NeoplasmsProto-Oncogene Proteins c-aktSignal TransductionT-LymphocytesXenograft Model Antitumor AssaysConceptsPancreatic cancerT cellsT cell-deficient miceTumor-infiltrating T cellsAntigen-experienced T cellsCell-deficient miceFavorable patient outcomesOrthotopic implantation modelComplete tumor regressionMost pancreatic cancersT cell surveillanceT cell recognitionPancreatic cancer cellsMHC class IAvailable immunotherapiesAdoptive transferEffective immunotherapyTumor immunogenicityTumor regressionPancreatic tumorsPatient outcomesHost miceImmunodeficient miceCell surveillanceTumorsTargeting the site encoded by SERPINA1*E342K for treating alpha‐1 antitrypsin deficiency‐associated liver diseases
Zhang X, Pham K, Li D, Schutte RJ, Brantly M, Liu C, Ostrov DA. Targeting the site encoded by SERPINA1*E342K for treating alpha‐1 antitrypsin deficiency‐associated liver diseases. FEBS Letters 2019, 593: 1849-1862. PMID: 31116417, DOI: 10.1002/1873-3468.13452.Peer-Reviewed Original ResearchIntegrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma
Hlady RA, Sathyanarayan A, Thompson JJ, Zhou D, Wu Q, Pham K, Lee J, Liu C, Robertson KD. Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma. Hepatology 2019, 69: 639-652. PMID: 30136421, PMCID: PMC6351162, DOI: 10.1002/hep.30211.Peer-Reviewed Original ResearchConceptsHistone modification profilesPromoter/enhancer functionGenome-wide assessmentTranscription of genesEpigenetic marksHistone modificationsEpigenome deregulationEpigenetic regulatorsBioinformatics strategyEpigenetic mechanismsModification profilesEpigenetic underpinningsLiver epigenomeEpigenetic profilesEnhancer functionEpigenetic parametersEpigenomeDecrease cell viabilityDriver lociSignificant deregulationCancer initiationTranscriptionHuman cancersCancer cell linesCell lines
2018
RET rearrangements are actionable alterations in breast cancer
Paratala BS, Chung JH, Williams CB, Yilmazel B, Petrosky W, Williams K, Schrock AB, Gay LM, Lee E, Dolfi SC, Pham K, Lin S, Yao M, Kulkarni A, DiClemente F, Liu C, Rodriguez-Rodriguez L, Ganesan S, Ross JS, Ali SM, Leyland-Jones B, Hirshfield KM. RET rearrangements are actionable alterations in breast cancer. Nature Communications 2018, 9: 4821. PMID: 30446652, PMCID: PMC6240119, DOI: 10.1038/s41467-018-07341-4.Peer-Reviewed Original ResearchMeSH KeywordsAnilidesAnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell Transformation, NeoplasticFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMiceMice, NudeMitogen-Activated Protein KinasesNIH 3T3 CellsNuclear Receptor CoactivatorsOncogene Proteins, FusionPhosphatidylinositol 3-KinasesPiperidinesProto-Oncogene Proteins c-retPyridinesQuinazolinesRas Guanine Nucleotide Exchange FactorsReceptor, ErbB-2Signal TransductionXenograft Model Antitumor AssaysConceptsBreast cancerRET amplificationRET gene alterationsMetastatic breast cancerNCOA4-RET fusionXenograft tumor formationPI3K pathwayRadiographic responseActionable alterationsLung cancerRET fusionsRET alterationsRET inhibitionIndex caseTherapeutic targetRET rearrangementsCancerGenomic profilingGene alterationsK pathwayTumor formationGene RETNon-tumorigenic cellsSubsequent treatmentOncogenic potential