Harlan Linver Pietz, MD, PhD
Hospital ResidentCards
About
Research
Publications
2025
Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2
Koide E, Pietz H, Beltran J, Chen J. Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2. Nature Communications 2025, 16: 484. PMID: 39779684, PMCID: PMC11711199, DOI: 10.1038/s41467-024-55810-w.Peer-Reviewed Original ResearchConceptsAutoinhibited stateR domainPost-translocation stateSubstrate-binding sitePre-translocation stateATP-binding siteProtein 2Nucleotide-binding domain 2Cryogenic electron microscopyStructural basisDiverse array of compoundsDomain 2Cryo-EMRegulation mechanismChemotherapeutic resistanceConformational changesMultidrug resistanceArray of compoundsDiverse arrayConformational statesLiver homeostasisMultidrug resistance-associated protein 2Initial transportSubstrateCytosol
2024
Psychological stress, cardiovascular disease and somatic pain in asylum seekers: a retrospective cross-sectional study
Lurie J, Pietz H, Hatef C, Taki F, Lee A, Virk S, Oren T, Gbekie C, Milewski A, Boyer R, Kaur G. Psychological stress, cardiovascular disease and somatic pain in asylum seekers: a retrospective cross-sectional study. Nature Mental Health 2024, 2: 1442-1450. DOI: 10.1038/s44220-024-00312-3.Peer-Reviewed Original ResearchSymptoms of psychological stressSomatic painCross-sectional studyCardiovascular diseasePsychological stressRetrospective cross-sectional studyStress symptomsCardiovascular disease symptomsChest painPain symptomsHealth outcomesCVD symptomsPainRisk factorsStroke symptomsMedical evaluationSymptomsAsylum seekersComorbidityPrevalenceComparative Analysis of Viral Load and Cytokines during SARS-CoV-2 Infection between Pregnant and Non-Pregnant Women
Liu D, Li H, Li X, Rodriguez G, Pietz H, Fiel R, Konadu E, Singh V, Loo F, Rodgers W. Comparative Analysis of Viral Load and Cytokines during SARS-CoV-2 Infection between Pregnant and Non-Pregnant Women. International Journal Of Molecular Sciences 2024, 25: 7731. PMID: 39062978, PMCID: PMC11277191, DOI: 10.3390/ijms25147731.Peer-Reviewed Original ResearchConceptsNon-pregnant womenSARS-CoV-2 infectionResponse to SARS-CoV-2 infectionPregnant womenViral loadNeutralizing antibodiesImmune response to SARS-CoV-2 infectionAnalysis of viral loadSARS-CoV-2Retrospective cohort studyIgG neutralizing antibodiesCytokine expression patternsMultiplex reverse transcription polymerase chain reactionAnti-N protein IgGExpression of leptinDifferential cytokine expressionEnhanced antibody productionReverse transcription polymerase chain reactionVulnerability of pregnant womenCytokine array assayTranscription polymerase chain reactionCytokine profileIncidence of SARS-CoV-2 infectionImmune modulationPolymerase chain reactionStructure-based discovery of CFTR potentiators and inhibitors
Liu F, Kaplan A, Levring J, Einsiedel J, Tiedt S, Distler K, Omattage N, Kondratov I, Moroz Y, Pietz H, Irwin J, Gmeiner P, Shoichet B, Chen J. Structure-based discovery of CFTR potentiators and inhibitors. Cell 2024, 187: 3712-3725.e34. PMID: 38810646, PMCID: PMC11262615, DOI: 10.1016/j.cell.2024.04.046.Peer-Reviewed Original ResearchConceptsLarge-scale dockingIon channel drug discoveryStructure-based discoveryStructure-based optimizationMedicinal chemistryTested ligandsMolecular dockingSmall moleculesDrug discoveryCystic fibrosis transmembrane conductance regulatorMoleculesAllosteric siteIonsDockingLigandSecretory diarrheaCystic fibrosisCystic fibrosis transmembrane conductance regulator modulatorsChemistryTransmembrane conductance regulatorSuboptimal pharmacokineticsCFTR potentiators
2023
A macrocyclic peptide inhibitor traps MRP1 in a catalytically incompetent conformation
Pietz H, Abbas A, Johnson Z, Oldham M, Suga H, Chen J. A macrocyclic peptide inhibitor traps MRP1 in a catalytically incompetent conformation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2220012120. PMID: 36893260, PMCID: PMC10089224, DOI: 10.1073/pnas.2220012120.Peer-Reviewed Original ResearchConceptsMultidrug resistance protein 1MRP1 overexpressionSubstrate transportAdenosine triphosphate-binding cassetteCatalytically incompetent conformationStructurally unrelated moleculesCpI1Small molecule inhibitorsAdenosine triphosphatePlasma membraneA-resolutionCryoelectron microscopyCryo-EMUnrelated moleculesConformational changesMultidrug resistanceMRP1 functionProtein 1Macrocyclic peptidesMultidrug transporter P-glycoproteinFlexible sidechainsXenobiotic compoundsNanomolar potencyCellular toxicityTherapeutic candidateSex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine
Cheung F, Apps R, Dropulic L, Kotliarov Y, Chen J, Jordan T, Langweiler M, Candia J, Biancotto A, Han K, Rachmaninoff N, Pietz H, Wang K, Tsang J, Cohen J. Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine. ELife 2023, 12: e80652. PMID: 36648132, PMCID: PMC9844983, DOI: 10.7554/elife.80652.Peer-Reviewed Original ResearchConceptsEarly innate responseVaccine recipientsPrior exposureInnate responseType I interferon signatureInfectious diseasesSeronegative vaccine recipientsType I IFN responseEarly antiviral responseNational InstituteInnate immune responseSystems immunology approachI IFN responseAdaptive immune phenotypesIntramural Research ProgramInterferon signatureAntibody titersVaccine trialsImmune phenotypeVirus vaccineNaive womenImmune responseSanofi PasteurDay 1Herpesvirus vaccine
2021
Serum and Cervicovaginal Fluid Antibody Profiling in Herpes Simplex Virus–Seronegative Recipients of the HSV529 Vaccine
Wang K, Dropulic L, Bozekowski J, Pietz H, Jegaskanda S, Dowdell K, Vogel J, Garabedian D, Oestreich M, Nguyen H, Ali M, Lumbard K, Hunsberger S, Reifert J, Haynes W, Sawyer J, Shon J, Daugherty P, Cohen J. Serum and Cervicovaginal Fluid Antibody Profiling in Herpes Simplex Virus–Seronegative Recipients of the HSV529 Vaccine. The Journal Of Infectious Diseases 2021, 224: 1509-1519. PMID: 33718970, PMCID: PMC8599754, DOI: 10.1093/infdis/jiab139.Peer-Reviewed Original ResearchConceptsVaccine recipientsHSV-2Genital tractNatural killer (NK) cell activityCell activationHerpes simplex virus type 2Replication-defective vaccinesNK cell activitySerum neutralizing antibody responsesNeutralizing antibody responsesAntibodies to epitopesCervicovaginal fluidGenital infectionGenital herpesAntibody profilesNeutralization titersHSV529Antibody responseSerum antibodiesHerpesType 2GD antibodiesAntibodiesSerumVaccine
2019
A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection
Dropulic L, Oestreich M, Pietz H, Laing K, Hunsberger S, Lumbard K, Garabedian D, Turk S, Chen A, Hornung R, Seshadri C, Smith M, Hosken N, Phogat S, Chang L, Koelle D, Wang K, Cohen J. A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection. The Journal Of Infectious Diseases 2019, 220: 990-1000. PMID: 31058977, PMCID: PMC6688060, DOI: 10.1093/infdis/jiz225.Peer-Reviewed Original ResearchConceptsHerpes simplex virus 2T cell responsesCD4+ T cell responsesHerpes simplex virusDose of vaccinePlacebo recipientsDouble-blindCD8+ T cell responsesReplication-defective herpes simplex virusSolicited injection site reactionsHerpes simplex virus infectionThird dose of vaccineSystemic reactions to vaccinationPlacebo-controlled trialPhase 1 studyInjection site reactionsNeutralizing antibody titersPlacebo-ControlledGenital herpesThird doseSite reactionsSimplex virusVaccine recipientsNeutralizing antibodiesReactions to vaccination
2017
A Replication-Defective Herpes Simplex Virus (HSV)-2 Vaccine, HSV529, is Safe and Well-Tolerated in Adults with or without HSV Infection and Induces Significant HSV-2-Specific Antibody Responses in HSV Seronegative Individuals
Dropulic L, Wang K, Oestreich M, Pietz H, Garabedian D, Jegaskanda S, Dowdell K, Nguyen H, Laing K, Koelle D, Azose A, Hunsberger S, Lumbard K, Chen A, Chang L, Phogat S, Cohen J. A Replication-Defective Herpes Simplex Virus (HSV)-2 Vaccine, HSV529, is Safe and Well-Tolerated in Adults with or without HSV Infection and Induces Significant HSV-2-Specific Antibody Responses in HSV Seronegative Individuals. Open Forum Infectious Diseases 2017, 4: s415-s416. PMCID: PMC5630753, DOI: 10.1093/ofid/ofx163.1041.Peer-Reviewed Original ResearchT cell assaysThird dose of vaccineDose of vaccineAntibody dependent cellular cytotoxicityT cell responsesGroup 3 subjectsSanofi PasteurGroup 1Placebo recipientsThird doseSeronegative individualsVaccine recipientsHSV-2-specific antibody responsesSolicited injection site reactionsCD8 T cell responsesCD4 T cell responsesGroup 3Systemic reactionsADCC-mediating antibodiesPlacebo-controlled trialHSV-2 vaccinesSolicited systemic reactionsInjection site reactionsDependent cellular cytotoxicityCellular immune responses
2016
765. Detection of Treatment-Resistant Infectious HIV After Genome-Directed Antiviral Endonuclease Therapy
Stone D, De Silva Feelixge H, Pietz H, Roychoudhury P, Greninger A, Schiffer J, Aubert M, Jerome K. 765. Detection of Treatment-Resistant Infectious HIV After Genome-Directed Antiviral Endonuclease Therapy. Molecular Therapy 2016, 24: s303. DOI: 10.1016/s1525-0016(16)33573-0.Peer-Reviewed Original Research