Joseph N. Contessa, MD, PhD
Professor Adjunct of Therapeutic RadiologyCards
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Professor Adjunct of Therapeutic Radiology
Biography
Joseph N. Contessa, MD, PhD, a radiation oncologist, is the director of Yale Medicine’s Central Nervous System Radiotherapy Program. He specializes in treating patients with primary tumors of the brain, head and neck, and at the base of the skull.
“Due to Yale's large referral base, I frequently see relatively rare tumors,” he says, including low-grade and malignant gliomas, ependymomas, high-grade meningiomas, hemangiopericytomas, paragangliomas, and schwannomas. His expertise in treating uncommon cancers benefits patients diagnosed with these tumor types. “I look forward to helping patients have the best possible outcome when they are faced with a challenging diagnosis,” he says.
Dr. Contessa is a Professor of therapeutic radiology and of pharmacology at Yale School of Medicine where he is part of a team of physicians and scientists who are actively researching the cellular mechanisms that tumors use to evade or “outsmart” standard cancer therapies in hopes of identifying new approaches that improve treatment.
“We are all working together to increase our knowledge, improve our care and beat cancer,” Dr. Contessa says.
Appointments
Therapeutic Radiology
Professor AdjunctPrimaryPharmacology
ProfessorSecondary
Other Departments & Organizations
- Brain Tumor Center
- Central Nervous System Radiotherapy
- Discovery to Cure Internship
- DNA Damage and Genome Integrity
- Gamma Knife Center
- Head & Neck Radiotherapy
- Head and Neck Cancers Program
- Head and Neck SPORE
- Molecular Medicine, Pharmacology, and Physiology
- Pharmacology
- Program in Translational Biomedicine (PTB)
- Spine Radiosurgery
- Therapeutic Radiology
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
Education & Training
- Resident
- The University of Michigan (2009)
- Intern
- The University of Michigan (2005)
- PhD
- Medical College of Virginia Commonwealth Universit (2004)
- MD
- Medical College of Virginia Commonwealth Universit (2004)
Research
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Overview
Therapeutic approaches for the treatment of EGFR and FGFR addicted lung cancer
Radiosensitization of malignant gliomas
Novel small molecule inhibitors of N-linked glycosylation
Molecular Imaging of the Epidermal Growth Factor Receptor
Drug Discovery and High Throughput Screening
Targeted therapy for head and neck squamous cell carcinoma
Medical Research Interests
ORCID
0000-0001-9408-1865
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Veronica Chiang, MD, FAANS
Barbara Burtness, MD
Kimberly L. Johung, MD, PhD
Scott Gettinger, MD
Thomas Hayman, MD, PhD
Abhijit Patel, MD, PhD
Publications
2025
Redundancy of the OST catalytic subunit facilitates therapeutic targeting of N-glycosylation
Baro M, Lee H, Kelley V, Lou R, Phoomak C, Politi K, Zeiss C, Van Zandt M, Contessa J. Redundancy of the OST catalytic subunit facilitates therapeutic targeting of N-glycosylation. Cell Chemical Biology 2025, 32: 839-853.e6. PMID: 40494352, DOI: 10.1016/j.chembiol.2025.05.005.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsN-glycosylationTrafficking of cell surface receptorsInhibits N-glycosylationCell surface receptorsGlycan synthesisCatalytic subunitOligosaccharyltransferaseEnzymatic activitySurface receptorsSTT3BSTT3ACharacterized in vitroDownstream effectsLung cancer xenograftsTherapeutic targetPatient-derivedBiological activityTumor regressionCancer xenograftsSmall moleculesGrowth delayTherapeutic agentsGlycansPLK4 Inhibition as a Strategy to Enhance Non-Small Cell Lung Cancer Radiosensitivity.
Dominguez-Vigil I, Banik K, Baro M, Contessa J, Hayman T. PLK4 Inhibition as a Strategy to Enhance Non-Small Cell Lung Cancer Radiosensitivity. Molecular Cancer Therapeutics 2025, 24: 1350-1361. PMID: 40296663, PMCID: PMC12353405, DOI: 10.1158/1535-7163.mct-24-0978.Peer-Reviewed Original ResearchCitationsAltmetricConceptsNon-small cell lung cancerLung cancerCFI-400945Mitotic catastropheNon-small cell lung cancer radiosensitizationRadiosensitivity of NSCLC cell linesCentrosome amplificationRadiation-induced tumor growth delayPLK4 inhibitionCell deathCurative-intent chemoradiationIncreased G2/M cell cycle arrestPolo-like kinase 4Subtype of lung cancerCell lung cancerIncreased centrosome amplificationCancer-related mortalityG2/M cell cycle arrestNSCLC cell linesCell cycle phase distributionClinical trial evaluationTargeting PLK4NSCLC in vitroCell cycle arrestPotential therapeutic target
2024
Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells
Kentache T, Althoff C, Caligiore F, Souche E, Schulz C, Graff J, Pieters E, Stanley P, Contessa J, Van Schaftingen E, Matthijs G, Foulquier F, Bommer G, Wilson M. Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells. Journal Of Biological Chemistry 2024, 300: 107875. PMID: 39395802, PMCID: PMC11607601, DOI: 10.1016/j.jbc.2024.107875.Peer-Reviewed Original ResearchCitationsAltmetricConceptsLec9 cellsChinese hamster ovaryDolichol synthesisGlycosylation-deficient Chinese hamster ovaryLong-read whole-genome sequencingCell linesN-glycosylation machineryN-glycan synthesisN-glycosylation defectChinese hamster ovary cellsGenomic regionsDHRSXLec9Hamster ovary cellsGlycosylation defectsHuman enzymeMolecular causesSynthesis defectsDolicholSRD5A3Hamster ovaryLevels of dolicholOvary cellsPolyprenolsKinetic propertiesPositive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB
Lampson B, Ramίrez A, Baro M, He L, Hegde M, Koduri V, Pfaff J, Hanna R, Kowal J, Shirole N, He Y, Doench J, Contessa J, Locher K, Kaelin W. Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB. Cell 2024, 187: 2209-2223.e16. PMID: 38670073, PMCID: PMC11149550, DOI: 10.1016/j.cell.2024.03.022.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsWhole-genome CRISPR-Cas9 screenCRISPR-Cas9 screensCryoelectron microscopy studiesCell surface localizationLipopolysaccharide receptor Toll-like receptor 4OST complexToll-like receptor 4CRISPR screensNF-kBCatalytic subunitN-glycosylationActivate NF-kBBase editorsUncompetitive inhibition mechanismNGI-1Molecular mechanismsCatalytic siteLPS-treated cellsOligosaccharyltransferaseDruggable pocketSTT3AReceptor Toll-like receptor 4Drug mechanism of actionStructural studiesInflammatory signaling
2023
In Vivo Verification of Electron Paramagnetic Resonance Biodosimetry Using Patients Undergoing Radiation Therapy Treatment
Draeger E, Roberts K, Decker R, Bahar N, Wilson L, Contessa J, Husain Z, Williams B, Flood A, Swartz H, Carlson D. In Vivo Verification of Electron Paramagnetic Resonance Biodosimetry Using Patients Undergoing Radiation Therapy Treatment. International Journal Of Radiation Oncology • Biology • Physics 2023, 119: 292-301. PMID: 38072322, DOI: 10.1016/j.ijrobp.2023.11.029.Peer-Reviewed Original ResearchCitationsConceptsHealthy volunteersDose rangeTotal body irradiationTotal body irradiation treatmentSignificant correlationRadiation therapy patientsPatient ageBody irradiationImmediate triageTherapy patientsClinical conditionsParticipants' teethPatientsNeck patientsUnknown dosesDosePatient dataRadiotherapy treatmentRadiation doseTeethTreatmentVolunteersSubsequent fractionsLuminescent dosimetersRadiation responseER chaperones use a protein folding and quality control glyco-code
Guay K, Ke H, Canniff N, George G, Eyles S, Mariappan M, Contessa J, Gershenson A, Gierasch L, Hebert D. ER chaperones use a protein folding and quality control glyco-code. Molecular Cell 2023, 83: 4524-4537.e5. PMID: 38052210, PMCID: PMC10790639, DOI: 10.1016/j.molcel.2023.11.006.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and Concepts
2021
The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress
Phoomak C, Cui W, Hayman TJ, Yu SH, Zhao P, Wells L, Steet R, Contessa JN. The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress. Science Advances 2021, 7: eabc6364. PMID: 33523898, PMCID: PMC7810369, DOI: 10.1126/sciadv.abc6364.Peer-Reviewed Original ResearchCitationsAltmetricConceptsTranslocon-associated proteinN-glycosylationER stressER glycoprotein quality controlTranslocon-associated protein complexEndoplasmic reticulum (ER) homeostasisAberrant N-glycosylationGlycoprotein quality controlER chaperone BiPFluorescence-based strategyProtein complexesPosttranslational modificationsChaperone BiPTRAP complexGlycosylation defectsConditions of stressRegulatory roleTranscriptional signatureIndividual cellsDownstream ERProtein levelsSubunitsSSR3GlycosylationCellsHypoxia-Guided Therapy for Human Papillomavirus-Associated Oropharynx Cancer
Burtness B, Contessa J. Hypoxia-Guided Therapy for Human Papillomavirus-Associated Oropharynx Cancer. Journal Of The National Cancer Institute 2021, 113: 652-653. PMID: 33429429, PMCID: PMC8168139, DOI: 10.1093/jnci/djaa187.Peer-Reviewed Original ResearchAltmetric
2019
Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma
Baro M, Lopez Sambrooks C, Burtness BA, Lemmon MA, Contessa JN. Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma. Molecular Cancer Therapeutics 2019, 18: 2124-2134. PMID: 31387891, PMCID: PMC6825559, DOI: 10.1158/1535-7163.mct-19-0163.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsMeSH KeywordsAnimalsAntibodies, MonoclonalCell Line, TumorCell ProliferationCell SurvivalCetuximabDrug Resistance, NeoplasmFemaleHead and Neck NeoplasmsHumansMiceNeuregulinsProto-Oncogene Proteins c-aktReceptor, ErbB-3Signal TransductionSquamous Cell Carcinoma of Head and NeckUp-RegulationXenograft Model Antitumor AssaysConceptsNeck squamous cell carcinomaSquamous cell carcinomaTherapeutic resistanceCell carcinomaResistant cellsConcentrations of cetuximabEFM-19 cellsCetuximab-resistant cellsActionable therapeutic targetsHNSCC cell linesTumor growth experimentsInhibition of EGFRErbB3 antibodyNeuregulin expressionOverall survivalTreatment regimensCetuximab resistanceTherapeutic targetAutocrine loopLocal controlTumor growthRadiotherapyEGFR inhibitionCetuximabNeuregulin SignalingSelective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing
Klaver E, Zhao P, May M, Flanagan-Steet H, Freeze HH, Gilmore R, Wells L, Contessa J, Steet R. Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing. Disease Models & Mechanisms 2019, 12: dmm039602. PMID: 31101650, PMCID: PMC6602306, DOI: 10.1242/dmm.039602.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNull cellsReceptor processingEndoplasmic reticulum localizationGlycan site occupancyInsulin-like growth factor 1 receptorReceptor tyrosine kinasesGrowth factor 1 receptorFactor 1 receptorCell surface glycoproteinMutant cellsNGI-1Catalytic subunitReceptor kinaseGlycosylation statusReduced abundanceTyrosine kinaseGlycan occupancyTyrosine receptor kinaseSurface localizationInsulin receptorAbnormal glycosylationProteolytic processingFunctional consequencesCell surfaceGlycosylation
Clinical Trials
Current Trials
Determining Mechanisms of Sensitivity and Resistance to Anti-Cancer Therapy for Advanced Lung Cancer
HIC ID1603017333RoleSub InvestigatorPrimary Completion Date06/20/2026Recruiting Participants
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