2024
Prodrug nanotherapy demonstrates in vivo anticryptosporidial efficacy in a mouse model of chronic Cryptosporidium infection
Ranjan A, Czyzyk D, Martinez-Traverso G, Sadiqova A, Valhondo M, Schaefer D, Spasov K, Jorgensen W, Vishwanatha J, Riggs M, Castellanos-Gonzalez A, Anderson K. Prodrug nanotherapy demonstrates in vivo anticryptosporidial efficacy in a mouse model of chronic Cryptosporidium infection. RSC Pharmaceutics 2024 PMID: 39372445, PMCID: PMC11447440, DOI: 10.1039/d4pm00093e.Peer-Reviewed Original ResearchProof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
Papini C, Ullah I, Ranjan A, Zhang S, Wu Q, Spasov K, Zhang C, Mothes W, Crawford J, Lindenbach B, Uchil P, Kumar P, Jorgensen W, Anderson K. Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2320713121. PMID: 38621119, PMCID: PMC11046628, DOI: 10.1073/pnas.2320713121.Peer-Reviewed Original ResearchConceptsDirect-acting antiviralsSARS-CoV-2Lack of off-target effectsIn vitro pharmacological profileTreatment of patientsDevelopment of severe symptomsPharmacological propertiesDrug-drug interactionsSARS-CoV-2 infectionProof-of-concept studySARS-CoV-2 M<sup>pro</sup>.Combination regimenImmunocompromised patientsLead compoundsSARS-CoV-2 main proteaseOral doseActive drugTreat infectionsPharmacological profileSARS-CoV-2 MPotential preclinical candidateOff-target effectsPatientsComplete recoveryCapsule formulation
2023
Exploring novel HIV‐1 reverse transcriptase inhibitors with drug‐resistant mutants: A double mutant surprise
Hollander K, Chan A, Frey K, Hunker O, Ippolito J, Spasov K, Yeh Y, Jorgensen W, Ho Y, Anderson K. Exploring novel HIV‐1 reverse transcriptase inhibitors with drug‐resistant mutants: A double mutant surprise. Protein Science 2023, 32: e4814. PMID: 37861472, PMCID: PMC10659932, DOI: 10.1002/pro.4814.Peer-Reviewed Original ResearchConceptsHIV drug developmentReverse transcriptaseHIV-1 reverse transcriptaseNew RT inhibitorsDrug-resistant mutantsLifelong treatmentHIV-1 reverseRT inhibitorsClinical isolatesPreclinical candidateResistance mutationsResistant variantsSuccessful managementMolecular cloneFirst-generation inhibitorsDrug developmentV106ASame mutationCandidate compoundsGeneration inhibitorsInhibitorsKey targetCatechol diethersA High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening
Fisher C, Medie F, Luu R, Gaibler R, Mulhern T, Miller C, Zhang C, Rubio L, Marr E, Vijayakumar V, Gabriel E, Quezada L, Zhang C, Anderson K, Jorgensen W, Alladina J, Medoff B, Borenstein J, Gard A. A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening. Cells 2023, 12: 2639. PMID: 37998374, PMCID: PMC10669988, DOI: 10.3390/cells12222639.Peer-Reviewed Original ResearchConceptsChip platformHigh-throughput organSARS-CoV-2 infectionHigh throughputScreening applicationsDisease modelingEfficacy of remdesivirNative virusRobust viral replicationSARS-CoV-2Therapeutic screeningPlatformRapid developmentAntiviral effectLung tissuePreclinical modelsEfficacious vaccineHuman donorsViral replicationEffective therapeuticsPlaque assayAntiviral studiesWorldwide pandemicThroughputRT-qPCRCovalent and noncovalent strategies for targeting Lys102 in HIV-1 reverse transcriptase
Prucha G, Henry S, Hollander K, Carter Z, Spasov K, Jorgensen W, Anderson K. Covalent and noncovalent strategies for targeting Lys102 in HIV-1 reverse transcriptase. European Journal Of Medicinal Chemistry 2023, 262: 115894. PMID: 37883896, PMCID: PMC10872499, DOI: 10.1016/j.ejmech.2023.115894.Peer-Reviewed Original ResearchNoncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors
Schrank T, Kothari A, Weir W, Stepp W, Rehmani H, Liu X, Wang X, Sewell A, Li X, Tasoulas J, Kim S, Yarbrough G, Xie Y, Flamand Y, Marur S, Hayward M, Wu D, Burtness B, Anderson K, Baldwin A, Yarbrough W, Issaeva N. Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216532120. PMID: 37523561, PMCID: PMC10410762, DOI: 10.1073/pnas.2216532120.Peer-Reviewed Original ResearchConceptsNF-κB-related genesEstrogen receptor alpha expressionDeintensification of therapyTreatment-related morbidityTumor-infiltrating CD4Receptor alpha expressionHPV carcinogenesisRadiosensitization of headOncogenic subtypesPIK3CA alterationsHNSCC tumorsPatient outcomesNeck tumorsT cellsTreatment responseHNSCC cellsTherapeutic intensityAtypical featuresIndependent cohortAlpha expressionNF-κBActive tumorTNF receptorTumorsPatient dataTackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy
Wang Z, Muthusamy V, Petrylak D, Anderson K. Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy. Npj Precision Oncology 2023, 7: 70. PMID: 37479885, PMCID: PMC10362036, DOI: 10.1038/s41698-023-00417-5.Peer-Reviewed Original ResearchBladder cancerBC cellsEarly phase clinical trialsPhase clinical trialsDurable responsesMetastatic diseaseMost patientsFGFR3 alterationsPrevalent malignancyClinical trialsFGFR3 fusionsPreclinical studiesFGFR inhibitorsHDAC inhibitorsFGFR3 expressionEfficient therapyTherapyCancerQuisinostatFGFR3New mechanistic insightsInhibitorsCellsPatientsMalignancyDesign, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase
Carter Z, Hollander K, Spasov K, Anderson K, Jorgensen W. Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 2023, 84: 129216. PMID: 36871704, PMCID: PMC10278203, DOI: 10.1016/j.bmcl.2023.129216.Peer-Reviewed Original Research
2018
Yale Cancer Center Precision Medicine Tumor Board: one tumour, multiple targets
Stewart T, Finberg K, Walther Z, Sklar JL, Hafez N, Eder JP, Anderson K, Wilson F, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: one tumour, multiple targets. The Lancet Oncology 2018, 19: 1567-1568. PMID: 32956641, DOI: 10.1016/s1470-2045(18)30759-9.Peer-Reviewed Case Reports and Technical NotesAPOBEC as an Endogenous Mutagen in Cancers of the Head and Neck
Sasaki T, Issaeva N, Yarbrough W, Anderson K. APOBEC as an Endogenous Mutagen in Cancers of the Head and Neck. Current Cancer Research 2018, 275-292. DOI: 10.1007/978-3-319-78762-6_10.Peer-Reviewed Original ResearchDiverse physiological processesFamily of cytidineApolipoprotein B mRNA-editing enzyme catalytic polypeptideEnzyme catalytic polypeptideU conversionBioinformatics studiesEndogenous mutagensAPOBEC3 functionGenomic DNAPhysiological processesCatalytic polypeptideEditing mechanismBioinformatics dataAPOBEC activityHuman cancersTarget nucleotidesProduction of neoantigensAPOBEC3 proteinsDiverse cancersSquamous cell carcinomaHuman papillomavirus expressionTherapeutic avenuesProteinStructural evidenceDNA
2017
Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR
Anderson K. Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR. Protein Engineering Design And Selection 2017, 30: 253-261. PMID: 28338744, PMCID: PMC6438133, DOI: 10.1093/protein/gzx004.Peer-Reviewed Original ResearchConceptsBifunctional thymidylate synthase-dihydrofolate reductaseThymidylate synthase-dihydrofolate reductaseSubstrate channelingDihydrofolate reductaseN-terminal amino acid extensionAmino acid extensionDihydrofolate reductase domainThymidylate synthaseFolate metabolizing enzymesAcid extensionMonofunctional formsPolypeptide chainMutation analysisMolecular mechanismsMetabolic enzymesParasitic protozoaDNA synthesisFunctional regionsInhibitor designSpeciesEnzymeStructural similarityStructural studiesEfficient catalysisLeishmania major
2016
Data publication with the structural biology data grid supports live analysis
Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, Chang CI, Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferré-D'Amaré AR, Christopher Fromme J, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P. Data publication with the structural biology data grid supports live analysis. Nature Communications 2016, 7: 10882. PMID: 26947396, PMCID: PMC4786681, DOI: 10.1038/ncomms10882.Peer-Reviewed Original ResearchConceptsData gridData publicationData setsGlobal data accessPrimary experimental data setsBiomedical data setsData accessExperimental data setsImage dataDissemination systemPilot collectionProcessing methodsGridSetData analysisAccessParadigm shiftDynamic bodyScientific publicationsSBDGServicesInformationCrystallographic data sets
2015
Human PrimPol: A Novel Mechanism of Antiviral Toxicity
Mislak A, Anderson K. Human PrimPol: A Novel Mechanism of Antiviral Toxicity. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.710.23.Peer-Reviewed Original ResearchNucleoside reverse transcriptase inhibitorsAntiviral toxicityHIV-1HIV-1-infected patientsNRTI-associated mitochondrial toxicityDaily drug regimensHIV-1 infectionLife-long administrationReverse transcriptase inhibitorsReduced viral loadReverse transcriptasePrevent viral transmissionDrug regimensViral loadTranscriptase inhibitorsRelated morbidityInfected patientsSevere mitochondrial dysfunctionSide effectsPatient adherenceViral replicationMechanisms of toxicityMitochondrial toxicityViral transmissionPatientsBiochemical and Functional Characterization of the Mutagenic Cytidine Deaminase, APOBEC3B
Sasaki T, Anderson K. Biochemical and Functional Characterization of the Mutagenic Cytidine Deaminase, APOBEC3B. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.573.48.Peer-Reviewed Original ResearchBiochemical experimentsMolecular mechanismsCytidine deaminaseFamily proteinsRNA editingBind DNANon-small cell lung cancerFunctional characterizationCellular cytidine deaminasesDiverse rolesEnzymatic capacityPhysiological processesPolypeptide 3APOBEC3BProteinProtein levelsSquamous cell lung carcinomaDeaminaseCatalytic polypeptide 3Cell lung carcinomaCell lung cancerCarcinogenesisTargeted treatment strategiesLung carcinomaTargeted therapy
2014
Recent Findings on the Mechanisms Involved in Tenofovir Resistance
Iyidogan P, Anderson K. Recent Findings on the Mechanisms Involved in Tenofovir Resistance. Antiviral Chemistry And Chemotherapy 2014, 23: 217-222. PMID: 23744599, PMCID: PMC4077986, DOI: 10.3851/imp2628.Peer-Reviewed Original ResearchConceptsReverse transcriptase inhibitorsDrug resistanceResistance mechanismsNon-nucleoside reverse transcriptase inhibitorsHIV-1 infectionLong-term efficacyMechanism of RTSynergistic antiviral effectTenofovir resistanceAntiretroviral agentsCombination therapyTreatment failureAntiviral synergySafety profileTranscriptase inhibitorsHIV-1TenofovirClinical useAntiviral effectTherapyViral sequencesNucleotide analoguesRegimensEfavirenzCurrent Perspectives on HIV-1 Antiretroviral Drug Resistance
Iyidogan P, Anderson K. Current Perspectives on HIV-1 Antiretroviral Drug Resistance. Viruses 2014, 6: 4095-4139. PMID: 25341668, PMCID: PMC4213579, DOI: 10.3390/v6104095.Peer-Reviewed Original ResearchTemporal resolution of protein signaling (473.1)
Anderson K, Sohl C, Luo B, Mo S, Kim Y, Apetri M, Lew E, Furdui C, Schlessinger J. Temporal resolution of protein signaling (473.1). The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.473.1.Peer-Reviewed Original ResearchReceptor tyrosine kinasesProtein signalingMultiple signal transduction pathwaysSpecific tyrosine residuesSignal transduction pathwaysSingle receptor tyrosine kinaseCellular processesTyrosine autophosphorylationOncogenic formsTransduction pathwaysRTK activityPhosphorylation modificationMutant formsReceptor dimerizationTyrosine residuesLigand bindingMolecular mechanismsTyrosine kinaseFunctional understandingOncogenic behaviorMolecular signaturesMultiple developmental disordersEarly dynamic eventsCell proliferationEssential role
2013
Correction to Bifunctional Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Mechanism and Proof-of-Concept as a Novel Therapeutic Design Strategy
Bailey C, Sullivan T, Iyidogan P, Tirado-Rives J, Chung R, Ruiz-Caro J, Mohamed E, Jorgensen W, Hunter R, Anderson K. Correction to Bifunctional Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Mechanism and Proof-of-Concept as a Novel Therapeutic Design Strategy. Journal Of Medicinal Chemistry 2013, 56: 8953-8953. PMCID: PMC4301842, DOI: 10.1021/jm401535f.Peer-Reviewed Original ResearchDesign, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of HIV Reverse Transcriptase
Iyidogan P, Sullivan T, Chordia M, Frey K, Anderson K. Design, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of HIV Reverse Transcriptase. ACS Medicinal Chemistry Letters 2013, 4: 1183-1188. PMID: 24900627, PMCID: PMC4027223, DOI: 10.1021/ml4002979.Peer-Reviewed Original ResearchH-phosphonatesLow nanomolar antiviral potencyReduced HIV replicationInhibitors of HIV reverse transcriptasePolymethylene linkerHIV replicationTMC derivativesAnti-HIV agentsAntiviral evaluationAntiviral activity profileChimeric inhibitorsHIV reverse transcriptaseCell-based assaysAntiviral potencyReverse transcriptaseIC50 valuesCellular levelNucleosideInhibitorsThymidinePolymethylene
2012
Pre-steady state kinetic analysis of cyclobutyl derivatives of 2′-deoxyadenosine 5′-triphosphate as inhibitors of HIV-1 reverse transcriptase
Kim J, Wang L, Li Y, Becnel K, Frey K, Garforth S, Prasad V, Schinazi R, Liotta D, Anderson K. Pre-steady state kinetic analysis of cyclobutyl derivatives of 2′-deoxyadenosine 5′-triphosphate as inhibitors of HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 2012, 22: 4064-4067. PMID: 22595174, PMCID: PMC3362660, DOI: 10.1016/j.bmcl.2012.04.078.Peer-Reviewed Original Research