Karen Anderson, PhD
Professor of Pharmacology and of Molecular Biophysics and BiochemistryCards
About
Research
Overview
Our research is directed toward understanding molecular mechanism of clinically important antimicrobial, anticancer, and antiviral molecular targets with the ultimate goal of developing more effective therapies. Key enzyme targets for the development of therapeutics include: KDO8P synthase (an important target for new antibacterials) and a bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) enzyme from parasites (a target for new antiparasitic drugs).
Also ongoing are studies to understanding the molecular mechanisms of normal and aberrant protein signaling and the effects of selectively guided anticancer drugs such as Iressa and Gleevec. Important molecular targets include EGFR, HER-2, PDGFRb, and c-kit receptor tyrosine kinases. Another area of focus involves investigating the mechanisms of HIV reverse transcriptase as well as drug resistance and toxicity that may ultimately aid in the design of better therapeutic agents for the treatment of AIDS.
Also ongoing are studies to understanding the molecular mechanisms of normal and aberrant protein signaling and the effects of selectively guided anticancer drugs such as Iressa and Gleevec. Important molecular targets include EGFR, HER-2, PDGFRb, and c-kit receptor tyrosine kinases. Another area of focus involves investigating the mechanisms of HIV reverse transcriptase as well as drug resistance and toxicity that may ultimately aid in the design of better therapeutic agents for the treatment of AIDS.
Medical Research Interests
Anti-Retroviral Agents; HIV Reverse Transcriptase; Molecular Biology; Multifunctional Enzymes; Pharmacology
Publications
2025
Precision projections of the delay of resistance mutations in non-small cell lung cancer via suppression of APOBEC
Nousias O, Mandell J, Anderson K, Townsend J. Precision projections of the delay of resistance mutations in non-small cell lung cancer via suppression of APOBEC. Lung Cancer 2025, 202: 108487. PMID: 40090261, DOI: 10.1016/j.lungcan.2025.108487.Peer-Reviewed Original ResearchNon-small cell lung cancer patientsNon-small cell lung cancerCell lung cancer patientsCell lung cancerLung cancer patientsEvolution of drug resistanceLung cancerDrug resistanceCancer patientsTyrosine kinase inhibitor therapyKinase inhibitor therapyTyrosine kinase inhibitorsPersonalized therapeutic strategiesTKI therapyInhibitor therapyTherapeutic failureResistance mutationsTherapeutic efficacyKinase inhibitorsAPOBEC mutationsTherapeutic strategiesTreatment efficacyCancer progressionImprove outcomesCancerExploring Possible Drug-Resistant Variants of SARS-CoV‑2 Main Protease (Mpro) with Noncovalent Preclinical Candidate, Mpro61
Kenneson J, Papini C, Tang S, Huynh K, Zhang C, Jorgensen W, Anderson K. Exploring Possible Drug-Resistant Variants of SARS-CoV‑2 Main Protease (Mpro) with Noncovalent Preclinical Candidate, Mpro61. ACS Bio & Med Chem Au 2025, 5: 215-226. PMID: 39990941, PMCID: PMC11843330, DOI: 10.1021/acsbiomedchemau.4c00109.Peer-Reviewed Original ResearchDrug resistance mutationsViral passaging experimentsDrug-resistant clinical isolatesCOVID infectionDrug-resistant variantsSARS-CoV-2 MClinical isolatesPassage experimentsIncreased up to 10-foldClinical useSARS-CoV-2 main proteaseWild typePreclinical candidateDouble variantInhibitorsMutationsDrug developmentInfectionNirmatrelvirMain proteaseProlonged usageMedicinal chemistry modificationsVariantsTarget-based approachPatients
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, 1: 963-975. 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
Academic Achievements & Community Involvement
News
News
- April 23, 2024
A Better COVID Treatment for the Immunocompromised?
- April 15, 2024
Treatments Found in Translational Science
- July 31, 2023
Researchers Develop a New Way to Classify HPV-Associated Head and Neck Cancers
- July 13, 2021Source: News Wise
Scientists Repurpose Cancer and Seizure Medications to Aid in the Fight against COVID-19
Get In Touch
Contacts
Academic Office Number
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Mailing Address
Pharmacology
PO Box 208066, 333 Cedar Street
New Haven, CT 06520-8066
United States
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Locations
Department of Pharmacology
Academic Office
Sterling Hall of Medicine, B-Wing
333 Cedar Street, Ste B350b
New Haven, CT 06510
Events
May 20258Thursday
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