Joseph N. Contessa, MD, PhD
Professor of Therapeutic Radiology and of PharmacologyCards
About
Research
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
Chemicals and Drugs; Neoplasms; Radiobiology
Publications
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 ResearchLec9 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 ResearchConceptsWhole-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 ResearchHealthy 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 Research
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 ResearchTranslocon-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 Research
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 ResearchMeSH 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 ResearchConceptsNull 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
2018
Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors
Lopez Sambrooks C, Baro M, Quijano A, Narayan A, Cui W, Greninger P, Egan R, Patel A, Benes CH, Saltzman WM, Contessa JN. Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors. Cancer Research 2018, 78: canres.0505.2018. PMID: 30026325, PMCID: PMC6125176, DOI: 10.1158/0008-5472.can-18-0505.Peer-Reviewed Original ResearchConceptsMutant NSCLCMutant non-small cell lung cancerNon-small cell lung cancerSignificant tumor growth delayEGFR-TKI treatmentCell lung cancerTyrosine kinase inhibitor resistanceEGFR tyrosine kinase inhibitor resistanceLung cancer cell linesNGI-1Tumor growth delayEffective therapeutic targetCell linesKinase inhibitor resistanceTumor cell viabilityH1975 xenograftsCancer cell linesTKI treatmentComplex transmembrane proteinsEGFR-TKILung cancerTumor responseCell cycle arrestPreclinical modelsTherapeutic strategiesEditing N-Glycan Site Occupancy with Small-Molecule Oligosaccharyltransferase Inhibitors
Rinis N, Golden JE, Marceau CD, Carette JE, Van Zandt MC, Gilmore R, Contessa JN. Editing N-Glycan Site Occupancy with Small-Molecule Oligosaccharyltransferase Inhibitors. Cell Chemical Biology 2018, 25: 1231-1241.e4. PMID: 30078634, PMCID: PMC6337728, DOI: 10.1016/j.chembiol.2018.07.005.Peer-Reviewed Original ResearchConceptsNGI-1Cellular unfolded protein responseMultisubunit enzyme complexN-glycan site occupancyUnfolded protein responseSubset of glycoproteinsSubunit-specific inhibitorsSecretory pathwayCatalytic subunitProtein responseEnzyme complexTarget proteinsOligosaccharyltransferasePharmacologic inhibitionGlycosylationProteinCell modelBiological effectsInhibitorsStructure-activity relationshipsSTT3BSTT3APharmacological approachesSubunitsSite occupancy
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
Clinical Care
Overview
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 also an associate 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.
Clinical Specialties
Therapeutic Radiology
Fact Sheets
Gamma Knife Radiosurgery
Learn More on Yale MedicineRadiation Therapy with Gamma Knife
Learn More on Yale MedicineHead and Neck Cancer
Learn More on Yale MedicineMeningiomas
Learn More on Yale Medicine
Yale Medicine News
News & Links
News
- November 11, 2024
Yale Cancer Answers with Dr. Joseph Contessa: Using Radiation to Treat Rare Brain Tumors
- May 28, 2021
Recent Research Sheds Light on Link Between Meningiomas and Seizures
- May 21, 2021
Faculty Entrepreneurs Receive Research Support from Blavatnik Fund for Innovation at Yale
- April 19, 2021
Yale Cancer Center Researchers Identify New Role for Immune-Boosting Protein “STING” in Treatment of Head and Neck Cancer
Get In Touch
Contacts
Academic Office Number
Appointment Number
Clinic Fax Number
Mailing Address
Therapeutic Radiology
PO Box 208040
New Haven, CT 06520-8040
United States
Locations
Yale Therapeutic Radiology
Academic Office
Hunter Building
15 York Street, Ste HRT 139
New Haven, CT 06510
Patient Care Locations
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Events
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