Elias Lolis, PhD
Professor of PharmacologyCards
Appointments
Additional Titles
Faculty Director, Office for Postdoctoral Affairs
Contact Info
Pharmacology
PO Box 208066, 333 Cedar Street
New Haven, CT 06520-8066
United States
Appointments
Additional Titles
Faculty Director, Office for Postdoctoral Affairs
Contact Info
Pharmacology
PO Box 208066, 333 Cedar Street
New Haven, CT 06520-8066
United States
Appointments
Additional Titles
Faculty Director, Office for Postdoctoral Affairs
Contact Info
Pharmacology
PO Box 208066, 333 Cedar Street
New Haven, CT 06520-8066
United States
About
Titles
Professor of Pharmacology
Faculty Director, Office for Postdoctoral Affairs
Biography
Elias Lolis received a BA degree in Chemistry at Columbia College and PhD in Chemistry from MIT training in structural biology. His postdoctoral training was in the Laboratory of Medical Biochemistry at Rockefeller University studying the functional interactions between advanced glycation endproducts (AGEs) and the immune system. He currently studies the mechanism of chemokines, the macrophage migration inhibitory factor (MIF) family of proteins, and their receptors in disease (cancer, inflammation, and infection) using structural biology, Crispr/Cas9 in mouse models of disease, and high throughput screening of small molecules as well as designing biotherapeutics. He received a Pharmaceutical Manufacturers Association Faculty Development Award in Basic Pharmacology, the Donaghue Young Investigator Award, and the GlaxoWellcome Award in Drug Discovery. He is the founder and co-founder of the Yale Macromolecular X-ray Facility and Yale Keck Bioinformatics Resource, respectively. More than 25 postdoctoral associates, seven PhD students, two postgrads, seven Yale undergraduates, ten under-represented minority summer students (BioStep and PREP), and 22 undergraduates and high school students from other schools were trained by him or his senior staff. He has been involved in the recruitment of under-represented minorities ever since he was an Assistant Professor traveling to various schools and conferences and, more recently, was a member of various committees of the 2020-21 and 2021-22 Intersections Science Fellows Symposium. He also serves as the Faculty Director of the Office for Postdoctoral Affairs for the University, his department's Director of Graduate Studies, and his department's Diversity, Equity, and Inclusion Committee, and mentors students and postdocs in his research lab.
Appointments
Pharmacology
ProfessorPrimary
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Developmental Therapeutics
- Lolis Lab
- Molecular Medicine, Pharmacology, and Physiology
- Pharmacology
- Primary Faculty
- Structural Biology
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
Education & Training
- Postdoc
- Rockefeller University (1991)
- PhD
- Massachusetts Institute of Technology, Biochemistry/Chemistry (1989)
- BA
- Columbia College (1984)
Research
Overview
We are generally interested in understanding the biology, structure, mechanism of action, and pharmacology (inhibition) of proteins in physiology and pathophysiology. Our studies are multidisciplinary and include structural biology (X-ray crystallography or NMR), molecular dynamics, high throughput screening (HPTS) and/or inhibitor design, mutational analysis, the use of strains of yeast expressing functional chemokine receptors for signaling and HTPS, and Crispr/Cas mice as a model system for models of disease.
Specific projects include:
1. Chemokine-chemokine receptor (GPCR) structures
2. High throughput screening to identify small molecule agonists and antagonists of chemokines and their GPCR receptors
3. Yeast genetics to identify and quantitate chemokine-chemokine receptor interactions
4. Mechanism of receptor activation for macrophage migration inhibitory factor
5. Identification of the substrate of MIF and structure of MIF-ligand complexes
6. Study of antagonists receptors in disease models
7. Co-crystal structures of other protein-inhibitors complexes
Medical Subject Headings (MeSH)
ORCID
0000-0002-7902-7868- View Lab Website
Lolis Lab
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Richard Bucala, MD, PhD
Victor Batista
Jimin Wang, PhD
Anton Bennett, PhD
Barbara Ehrlich, PhD
Buqu Hu
Crystallography, X-Ray
Inflammation
Neoplasms
Publications
2024
A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus
Li J, Leng L, Pantouris G, Manjula R, Piecychna M, Abriola L, Hu B, Lolis E, Armstrong M, Donnelly S, Bucala R. A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus. Journal Of Biological Chemistry 2024, 300: 107443. PMID: 38838773, PMCID: PMC11259703, DOI: 10.1016/j.jbc.2024.107443.Peer-Reviewed Original ResearchAltmetricConceptsPromoter microsatellitesGene expressionMicrosatellite repeat numberMacrophage migration inhibitory factorLength-dependent mannerRNA expression analysisSusceptibility lociFunctional variantsSmall molecule inhibitorsExpression analysisPharmacogenomic developmentRepeat numberMicrosatelliteFunctional interactionsTranscription inhibitorInflammatory gene expressionMIF mRNA expressionCytokine macrophage migration inhibitory factorTranscriptionGenesProtein expressionMigration inhibitory factorExpressionInhibitory factorExpressing macrophagesIguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose
Bloom J, Pantouris G, He M, Aljabari B, Mishra L, Manjula R, Parkins A, Lolis E, Al-Abed Y. Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose. Molecular Medicine 2024, 30: 43. PMID: 38539088, PMCID: PMC10976746, DOI: 10.1186/s10020-024-00803-0.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsMode of inhibitionAllosteric inhibitorsActive site pocketMigration inhibitory factorSite pocketInhibitory factorProtein crystallographyTautomerase active siteOxidative stressT-614Murine modelDrug modePleiotropic cytokineNon-competitive type of inhibitionAPAP overdoseActive siteMacrophage migration inhibitory factorInhibition constantType of inhibitionInhibitor of macrophage migration inhibitory factorKinetic analysisBackgroundMacrophage migration inhibitory factorAcetaminophen overdoseIn vivo experimentsMultiple small molecule inhibitors
2023
Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells
Spiller L, Manjula R, Leissing F, Basquin J, Bourilhon P, Sinitski D, Brandhofer M, Levecque S, Gerra S, Sabelleck B, Zhang L, Feederle R, Flatley A, Hoffmann A, Panstruga R, Bernhagen J, Lolis E. Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells. Science Signaling 2023, 16: eadg2621. PMID: 37988455, DOI: 10.1126/scisignal.adg2621.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsMammalian macrophage migration inhibitory factorHetero-oligomeric complexesHigh structural similarityMultifunctional inflammatory cytokineHuman lung epithelial cellsYeast reporter systemReporter systemLung epithelial cellsPlant leavesFunctional similarityCellular responsesHuman cellsPharmacological inhibitorsDopachrome tautomeraseFunctional implicationsX-ray crystallographyMacrophage migration inhibitory factorStructural similarityEpithelial cellsMigration inhibitory factorCXCR4 receptorProteinTautomerase activityCellsMIF receptorMapping N- to C-terminal allosteric coupling through disruption of a putative CD74 activation site in D-dopachrome tautomerase
Chen E, Widjaja V, Kyro G, Allen B, Das P, Prahaladan V, Bhandari V, Lolis E, Batista V, Lisi G. Mapping N- to C-terminal allosteric coupling through disruption of a putative CD74 activation site in D-dopachrome tautomerase. Journal Of Biological Chemistry 2023, 299: 104729. PMID: 37080391, PMCID: PMC10208890, DOI: 10.1016/j.jbc.2023.104729.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsEngineering of the high-affinity chemokine CXCL13 to screen CXCR5 antagonists to treat cancer and autoimmune diseases
Ramu M, Rosenberg E, Kartz S, Foss F, Lolis E. Engineering of the high-affinity chemokine CXCL13 to screen CXCR5 antagonists to treat cancer and autoimmune diseases. Biophysical Journal 2023, 122: 474a. DOI: 10.1016/j.bpj.2022.11.2542.Peer-Reviewed Original ResearchValproate-coenzyme A conjugate blocks opening of receptor binding domains in the spike trimer of SARS-CoV-2 through an allosteric mechanism
Maschietto F, Qiu T, Wang J, Shi Y, Allen B, Lisi G, Lolis E, Batista V. Valproate-coenzyme A conjugate blocks opening of receptor binding domains in the spike trimer of SARS-CoV-2 through an allosteric mechanism. Computational And Structural Biotechnology Journal 2023, 21: 1066-1076. PMID: 36688026, PMCID: PMC9841741, DOI: 10.1016/j.csbj.2023.01.014.Peer-Reviewed Original ResearchCitationsAltmetric
2022
A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding
Shillingford S, Zhang L, Surovtseva Y, Dorry S, Lolis E, Bennett AM. A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding. Journal Of Biological Chemistry 2022, 298: 102617. PMID: 36272649, PMCID: PMC9676401, DOI: 10.1016/j.jbc.2022.102617.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsMitogen-activated protein kinaseP38 mitogen-activated protein kinaseMAPK bindingRegulatory mechanismsAllosteric siteMKP family membersNovel allosteric siteSmall molecule targetingMAPK/JNKAdditional regulatory mechanismsPhosphatase functionPhosphatase domainP38 MAPK/JNKProtein kinaseMKP7Site mutantsMAPK signalingAllosteric pocketMolecule targetingMAPK dephosphorylationMutantsNovel siteJNKCatalytic siteDephosphorylationHow to correct relative voxel scale factors for calculations of vector-difference Fourier maps in cryo-EM
Wang J, Liu J, Gisriel CJ, Wu S, Maschietto F, Flesher DA, Lolis E, Lisi GP, Brudvig GW, Xiong Y, Batista VS. How to correct relative voxel scale factors for calculations of vector-difference Fourier maps in cryo-EM. Journal Of Structural Biology 2022, 214: 107902. PMID: 36202310, PMCID: PMC10226527, DOI: 10.1016/j.jsb.2022.107902.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsCryo-EM mapsAmino acid residuesAcid residuesCryo-electron microscopy mapIndividual amino acid residuesCyanobacteria Synechocystis spPCC 6803Synechocystis spMicroscopy mapsThermosynechococcus elongatusSARS-CoV-2 spike proteinLocal structural changesResiduesSpike proteinAtomic coordinatesElongatusSubunitsSpeciesProteinSpSimilar structureStructural changesDefining the structure-activity relationship for a novel class of allosteric MKP5 inhibitors
Gannam Z, Jamali H, Kweon OS, Herrington J, Shillingford SR, Papini C, Gentzel E, Lolis E, Bennett AM, Ellman JA, Anderson KS. Defining the structure-activity relationship for a novel class of allosteric MKP5 inhibitors. European Journal Of Medicinal Chemistry 2022, 243: 114712. PMID: 36116232, PMCID: PMC9830533, DOI: 10.1016/j.ejmech.2022.114712.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsStructure-Activity RelationshipConceptsStress-responsive MAPKsEnzyme-inhibitor complexDystrophic muscle diseasePhosphatase 5Muscle diseaseAllosteric inhibitorsNumber of diseasesNovel classProtein kinase phosphatase 5Structure-activity relationshipsPotential therapeutic targetMKP5X-ray crystal structureTherapeutic targetPotential therapeuticsInhibitorsLead compoundsInhibitionProper positioningMAPKCrystal structureMitogenTyr435Derivative compoundsInteractionStructural Insights into Binding of Remdesivir Triphosphate within the Replication–Transcription Complex of SARS-CoV‑2
Wang J, Shi Y, Reiss K, Maschietto F, Lolis E, Konigsberg WH, Lisi GP, Batista VS. Structural Insights into Binding of Remdesivir Triphosphate within the Replication–Transcription Complex of SARS-CoV‑2. Biochemistry 2022, 61: 1966-1973. PMID: 36044776, PMCID: PMC9469760, DOI: 10.1021/acs.biochem.2c00341.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsReplication-transcription complexStructural basisCryo-EM structureAdenosine monophosphateRemdesivir triphosphateStructural insightsDuplex productsPrimer extensionNucleotide selectivityBase pairsNucleotide incorporationIncoming substrateRibosyl moietyActive complexSARS-CoV-2 inhibitorsNew detailed informationTriphosphateComplexesMolecular dynamics simulationsAdenosine triphosphate
News
News
- July 09, 2024
Yale Researchers Pave Way To Target Autoimmune Disease-associated Gene Variant
- July 24, 2023
Lin Leng, Senior Research Scientist in Medicine (Rheumatology), Retires
- May 01, 2018
A Pathway Towards Better Therapies for T-Cell Lymphoma
- November 18, 2014
The 4th Yale Biophysics & Structural Biology Symposium
Get In Touch
Contacts
Pharmacology
PO Box 208066, 333 Cedar Street
New Haven, CT 06520-8066
United States
Administrative Support
Events
Yale Only Stavroula Hatzios, PhD