Susan Gueble, MD, PhD
Assistant Professor of Therapeutic RadiologyDownloadHi-Res Photo
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Assistant Professor of Therapeutic Radiology
Biography
Dr. Susan Gueble is a physician-scientist and Assistant Professor of Therapeutic Radiology. She received her MD and PhD degrees as part of the medical scientist training program (MSTP) at Yale School of Medicine and completed her residency in radiation oncology at Yale-New Haven Hospital. Her clinical focus is in caring for patients with gynecologic, prostate, or genitourinary malignancies using radiation treatment. Her primary clinical practice is in Trumbull, CT. Her research focuses on the mechanisms of novel DNA modifying agents and DNA damage response pathways, with the goal of translating her findings into therapeutic strategies for the treatment of cancer.
Appointments
Therapeutic Radiology
Assistant ProfessorPrimary
Other Departments & Organizations
- Janeway Society
- Radiobiology
- Radiobiology and Genome Integrity
- Therapeutic Radiology
- Yale Cancer Center
- Yale Medicine
Education & Training
- Resident
- Yale New Haven Hospital (2023)
- Chief Resident
- Yale-New Haven Hospital (2023)
- Intern
- Saint Mary's Hospital (2019)
- MD
- Yale School of Medicine (2018)
- PhD
- Yale University, Experimental Pathology (2018)
- BS
- Yale University, Physics, Molecular Biophysics & Biochemistry (2010)
Research
Overview
Medical Research Interests
Alkylating Agents; Antineoplastic Agents; Biomarkers; DNA Damage; DNA Repair; Gastrointestinal Neoplasms; Melanoma; Molecular Targeted Therapy; Radiation Oncology
ORCID
0000-0002-8043-1147
Research at a Glance
Yale Co-Authors
Frequent collaborators of Susan Gueble's published research.
Publications Timeline
A big-picture view of Susan Gueble's research output by year.
Research Interests
Research topics Susan Gueble is interested in exploring.
Ranjit S. Bindra, MD, PhD
Peter M. Glazer, MD, PhD
Juan Vasquez, MD
Kingson Lin, MD/PhD
Stephanie Halene, MD, Dr Med
Anna Marie Pyle, PhD
18Publications
1,008Citations
DNA Repair
DNA Damage
Biomarkers
Alkylating Agents
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 ResearchCitationsAltmetric
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, noae257. PMID: 39658092, DOI: 10.1093/neuonc/noae257.Peer-Reviewed Original ResearchAltmetricConceptsMedian 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 cellsGBM12712 Modeling response to alkylating chemotherapy in a syngeneic model of MMR-deficient glioma
Bhatt D, Sundaram R, López K, Friedman S, Gueble S, Bindra R, Vasquez J. 712 Modeling response to alkylating chemotherapy in a syngeneic model of MMR-deficient glioma. 2024, a814-a814. DOI: 10.1136/jitc-2024-sitc2024.0712.Peer-Reviewed Original ResearchO6-Guanine Targeting Novel DNA Cross-Linker and ATR Inhibitor Combination for MGMT-Silenced IDH1/2 Mutant Acute Myeloid Leukemia
Bhardwaj P, Sundaram R, Friedman S, Baassiri A, Matthews M, VanOudenhove J, Gueble S, Halene S, Bindra R. O6-Guanine Targeting Novel DNA Cross-Linker and ATR Inhibitor Combination for MGMT-Silenced IDH1/2 Mutant Acute Myeloid Leukemia. Blood 2024, 144: 6130. DOI: 10.1182/blood-2024-210621.Peer-Reviewed Original ResearchConceptsAML patient samplesHematologic adverse effectsMGMT promoter hypermethylationPatient-derived xenograftsDe novoMismatch repairO6 position of guaninePromoter hypermethylationMyelodysplastic syndromeRNA-seq analysisMyeloid leukemiaATR inhibitorsDNA repair proteinsClinical trialsSelection of mutationsFunctional mismatch repairPatient samplesMutant acute myeloid leukemiaBiomarker-targeted therapiesCell line pairsAlkylation DNA damageMutant IDH1/2 inhibitorsRNA-seqCases of AMLMGMT promoter methylationMechanism 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 ResearchCitationsAltmetricConceptsDNA 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 StatementsCitationsMeSH Keywords and ConceptsConceptsHomologous 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 StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsDNA 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDNA 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 ResearchCitationsAltmetricConceptsDouble-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 samples
Academic Achievements & Community Involvement
activity American Society for Radiation Oncology
Professional OrganizationsMemberDetails2019 - Presentactivity American Brachytherapy Society
Professional OrganizationsMemberDetails2023 - Presentactivity Radiation Research Society
Professional OrganizationsMemberDetails2023 - Presenthonor NIH Director's Early Independence Award
National AwardNational Institutes of HealthDetails09/20/2023United Stateshonor Spector Family Fund for Clinical Research and Investigation Award
Yale School of Medicine AwardYale Physician Scientist Development Award (YPSDA) and Yale Center for Clinical Investigation (YCCI) Scholars ProgramDetails07/01/2023
Clinical Care
Overview
Clinical Specialties
Gynecologic Radiotherapy; Prostate & Genitourinary Radiotherapy
Fact Sheets
Metastatic Cancer
Learn More on Yale MedicineCervical Dysplasia
Learn More on Yale MedicineBone Cancer
Learn More on Yale MedicineLow Bone Density
Learn More on Yale Medicine
Board Certifications
Radiation Oncology
- Certification Organization
- AB of Radiology
- Original Certification Date
- 2024
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Locations
Yale Therapeutic Radiology
Academic Office
Hunter Building
15 York Street, Ste 313C
New Haven, CT 06510
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