Susan Gueble, MD, PhD
Assistant Professor of Therapeutic RadiologyCards
About
Research
Overview
Medical Research Interests
Alkylating Agents; Antineoplastic Agents; Biomarkers; DNA Damage; DNA Repair; Gastrointestinal Neoplasms; Melanoma; Molecular Targeted Therapy; Radiation Oncology
Publications
Featured Publications
Mechanism-based design of agents that selectively target drug-resistant glioma
Lin K, Gueble SE, Sundaram RK, Huseman ED, Bindra RS, Herzon SB. Mechanism-based design of agents that selectively target drug-resistant glioma. Science 2022, 377: 502-511. PMID: 35901163, PMCID: PMC9502022, DOI: 10.1126/science.abn7570.Peer-Reviewed Original Research
2025
Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy
Bhatt D, Sundaram R, López K, Lee T, Gueble S, Vasquez J. Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy. Current Protocols 2025, 5: e70097. PMID: 39995104, DOI: 10.1002/cpz1.70097.Peer-Reviewed Original ResearchConceptsImproved response to immune checkpoint blockadeGlioma modelResponse to immune checkpoint blockadeAlkylating agentsImmune checkpoint blockadeIncrease tumor immunogenicityMurine glioma modelMurine glioma cell lineResponse to alkylating agentsResistance to temozolomideDNA repair genotypesMMR deficiencyAntitumor immunityCheckpoint blockadeTumor immunogenicityMedian survivalImmunocompetent modelDismal prognosisMismatch repairMismatch repair deficiencyGlioma cell linesIntracranial tumorsAlkylating chemotherapySomatic lossSomatic acquisition
2024
The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma
McCord M, Sears T, Wang W, Chaliparambil R, An S, Sarkaria J, James C, Ruggeri B, Gueble S, Bindra R, Horbinski C. The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma. Neuro-Oncology 2024, 27: 644-651. PMID: 39658092, PMCID: PMC11889708, DOI: 10.1093/neuonc/noae257.Peer-Reviewed Original ResearchMedian survival of miceSurvival of miceMedian survivalIDH wild-type glioblastomaO-6-methylguanine-DNA methyltransferaseExposure to temozolomideAcquired resistance to TMZWild-type glioblastomaPatient-derived xenograftsSensitivity to temozolomidePatient-derived modelsResistance to temozolomideLN229 glioma cellsPatient-derived glioblastomaRecurrent tumorsMGMT deficiencyFractionated RTTemozolomideLow dosesImprove outcomesGlioblastomaEnzyme deficiencyMismatch repairGlioma cellsGBM12Mechanism of Action of KL-50, a Candidate Imidazotetrazine for the Treatment of Drug-Resistant Brain Cancers
Huseman E, Lo A, Fedorova O, Elia J, Gueble S, Lin K, Sundaram R, Oh J, Liu J, Menges F, Rees M, Ronan M, Roth J, Batista V, Crawford J, Pyle A, Bindra R, Herzon S. Mechanism of Action of KL-50, a Candidate Imidazotetrazine for the Treatment of Drug-Resistant Brain Cancers. Journal Of The American Chemical Society 2024, 146: 18241-18252. PMID: 38815248, PMCID: PMC11409917, DOI: 10.1021/jacs.3c06483.Peer-Reviewed Original ResearchDNA repair capacityDifferential DNA repair capacityDNA interstrand cross-linksRepair capacityInterstrand cross-linksDisplacement of fluorideDNA repairCross-linkingAberrant DNA repairLesionsHealthy tissueBrain cancerRing openingHealthy cellsMGMTSelective chemotherapyGenotoxic agentsTumorChemical DNA modificationsCancerMultistep processRepair
2022
The Role of PARP Inhibitors in Patients with Primary Malignant Central Nervous System Tumors
Gueble SE, Vasquez JC, Bindra RS. The Role of PARP Inhibitors in Patients with Primary Malignant Central Nervous System Tumors. Current Treatment Options In Oncology 2022, 23: 1566-1589. PMID: 36242713, DOI: 10.1007/s11864-022-01024-5.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHomologous recombination deficiencyPrimary CNS tumorsCNS tumorsClinical trialsPARP inhibitorsPreclinical evidencePrimary malignant central nervous system tumorMalignant central nervous system tumorsCentral nervous system tumorsImmune checkpoint inhibitorsStandard treatment modalityInitial clinical trialsEarly phase trialsNervous system tumorsCentral nervous tumorsExtracranial cancerCheckpoint inhibitorsDevastating malignancyStandard therapyOngoing trialsCombination therapyTreatment optionsTreatment modalitiesSystem tumorsPhase trialsOncometabolites as Regulators of DNA Damage Response and Repair
Gueble SE, Bindra RS. Oncometabolites as Regulators of DNA Damage Response and Repair. Seminars In Radiation Oncology 2022, 32: 82-94. PMID: 34861999, DOI: 10.1016/j.semradonc.2021.09.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDNA damage responseDamage responseDDR defectsMultiple DNA repair pathwaysSynthetic lethal interactionsDNA repair pathwaysRepair pathwaysLethal interactionsDiverse mechanismsOncometaboliteCancer therapyCertain cancersNew mechanismTherapeutic strategiesSmall intermediatesBiologyRegulatorPathwayMechanismRepairDDRMetabolismDysregulationDefectsResponse
2019
Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51
Kaplan AR, Gueble SE, Liu Y, Oeck S, Kim H, Yun Z, Glazer PM. Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51. Science Translational Medicine 2019, 11 PMID: 31092693, PMCID: PMC6626544, DOI: 10.1126/scitranslmed.aav4508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBRCA1 ProteinBRCA2 ProteinCell Line, TumorDNA RepairDown-RegulationE2F4 Transcription FactorFemaleGene Expression Regulation, NeoplasticHumansMice, NudePoly(ADP-ribose) Polymerase InhibitorsQuinazolinesRad51 RecombinaseReceptors, Platelet-Derived Growth FactorTumor HypoxiaVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsHomology-directed DNA repairDNA repairE2F transcription factor 4Protein phosphatase 2ATranscription factor 4DNA repair inhibitorsPhosphatase 2ARAD51 recombinaseTranscriptional corepressorMouse tumor xenograftsSynthetic lethalityGene expressionRB2/Mouse bone marrowGrowth factor receptor inhibitionRepair inhibitorsUnknown mechanismPlatelet-derived growth factor receptor inhibitionFactor 4Human tumorsInhibitor olaparibPARP inhibitorsMutationsCombination of cediranibCancer therapy
2018
PTEN Regulates Non-Homologous End Joining by Epigenetic Induction of NHEJ1/XLF
Sulkowski PL, Scanlon SE, Oeck S, Glazer PM. PTEN Regulates Non-Homologous End Joining by Epigenetic Induction of NHEJ1/XLF. Molecular Cancer Research 2018, 16: molcanres.0581.2017. PMID: 29739874, PMCID: PMC6072556, DOI: 10.1158/1541-7786.mcr-17-0581.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksKey DNA repair pathwaysCytotoxic DNA lesionsXRCC4-like factorPatient-derived melanomasDNA repair pathwaysDouble-strand breaksNovel regulatory roleTumor suppressor geneSuppression of PTENHistone acetyltransferasesDSB repairGenomic analysisNHEJ defectsNonhomologous endRepair pathwaysGene promoterNovel functionRegulatory acetylationNHEJ deficiencyDNA lesionsRegulatory roleSuppressor geneNHEJ DSB repairNHEJ
2017
Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL-deficient human renal cell carcinoma
Scanlon SE, Hegan DC, Sulkowski PL, Glazer PM. Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL-deficient human renal cell carcinoma. Oncotarget 2017, 9: 4647-4660. PMID: 29435132, PMCID: PMC5797003, DOI: 10.18632/oncotarget.23470.Peer-Reviewed Original ResearchDouble-strand break repairDNA double-strand break repairBreak repairHomologous recombinationHomology-dependent DNA double-strand break repairGene expressionHuman clear cell renal carcinomaHuman renal cell carcinomaVon Hippel-Lindau (VHL) tumor suppressor geneDNA double-strand breaksDNA repair gene expressionHr gene expressionRadiation-induced DNA double-strand breaksImpaired DNA double-strand break repairPro-growth stateDouble-strand breaksDNA repair genesRepair gene expressionDNA repair defectsTumor suppressor genePARP inhibitor sensitivityRenal cancer cellsTranscriptional reprogrammingGene repressionRenal carcinoma samplesAnti-tumor Activity of miniPEG-γ-Modified PNAs to Inhibit MicroRNA-210 for Cancer Therapy
Gupta A, Quijano E, Liu Y, Bahal R, Scanlon SE, Song E, Hsieh WC, Braddock DE, Ly DH, Saltzman WM, Glazer PM. Anti-tumor Activity of miniPEG-γ-Modified PNAs to Inhibit MicroRNA-210 for Cancer Therapy. Molecular Therapy - Nucleic Acids 2017, 9: 111-119. PMID: 29246289, PMCID: PMC5633812, DOI: 10.1016/j.omtn.2017.09.001.Peer-Reviewed Original ResearchMiR-210Human tumor xenograftsAnti-tumor activityHistopathological analysisTherapeutic approachesMicroRNA-210Tumor xenograftsOncogenic miRTumor cellsHypoxic cellsAnticancer therapyHuman cancersCell proliferationCancer therapyConsiderable necrosisSignificant delayTherapyOncogenic microRNAsInhibition strategiesCellsMicroRNAsFibrosisXenograftsNecrosisTumors
Academic Achievements & Community Involvement
Clinical Care
Overview
Susan Gueble, MD, PhD, is a specialist in radiation oncology focusing on the care of patients with gynecologic, prostate, or genitourinary cancers. She utilizes a variety of radiation therapy techniques to manage these conditions.
Dr. Gueble says the most important part of her work is letting her patients know that she is there to listen to them and to truly understand their concerns.
“My goal is to help patients fully comprehend their diagnosis and treatment options so they can make informed decisions that are right for them,” she says. “Additionally, I work closely with a multidisciplinary team of specialists to ensure that each patient receives a comprehensive treatment plan tailored to their needs.”
As an assistant professor of therapeutic radiology at Yale School of Medicine, Dr. Gueble is involved in research exploring DNA modifying agents and DNA damage response pathways. Her work seeks to develop new therapeutic strategies for cancer treatment.
Dr. Gueble completed her medical training at Yale School of Medicine and underwent residency in radiation oncology at Yale New Haven Hospital. She has been recognized with the RSNA Roentgen Resident/Fellow Research Award by the Radiological Society of North America.
Clinical Specialties
Gynecologic Radiotherapy; Prostate & Genitourinary Radiotherapy; Therapeutic Radiology
Fact Sheets
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Yale Therapeutic Radiology
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Hunter Building
15 York Street, Ste 313C
New Haven, CT 06510
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