Elias Lolis, PhD
Professor of Pharmacology
Research & Publications
Biography
News
Research Summary
We are interested in understanding the mechanism of action of proteins involved in cancer, inflammation, and infectious disease using a variety of techniques including structural biology, yeast and mouse genetics, high throughput screening, and signal transduction. For example, we determined the three-dimensional structure of human, murine, and herpesvirus-8 chemokines are now determining how these proteins interact with their G-protein coupled receptor to develop a therapeutic target for oncology. We have been using macrophage migration inhibitory factor (MIF) from various pathogens to develop vaccine. We used small molecule inhibitors and are studying using some of them as reagents for probing signaling and others as therapeutics in mouse models of autoimmunity, inflammation, or infectious diseases.
Specialized Terms: Cancer; Inflammation; Infectious disease; Structural Biology; Signaling pathways; Drug design; High throughput screening (HTPS)
Extensive Research Description
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
Coauthors
Research Interests
Education; Immune System Diseases; Inflammation; Neoplasms; Parasitic Diseases; Pharmacology; Crystallography, X-Ray; Enzymes and Coenzymes; High-Throughput Screening Assays
Selected Publications
- Mapping N- to C-terminal allosteric coupling through disruption of a putative CD74 activation site in D-dopachrome tautomeraseChen 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.
- Engineering of the high-affinity chemokine CXCL13 to screen CXCR5 antagonists to treat cancer and autoimmune diseasesRamu 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.
- Valproate-coenzyme A conjugate blocks opening of receptor binding domains in the spike trimer of SARS-CoV-2 through an allosteric mechanismMaschietto 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.
- A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK bindingShillingford 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.
- How to correct relative voxel scale factors for calculations of vector-difference Fourier maps in cryo-EMWang 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.
- Defining the structure-activity relationship for a novel class of allosteric MKP5 inhibitorsGannam 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.
- Structural Insights into Binding of Remdesivir Triphosphate within the Replication–Transcription Complex of SARS-CoV‑2Wang 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.
- Insights into Binding of Single-Stranded Viral RNA Template to the Replication–Transcription Complex of SARS-CoV‑2 for the Priming Reaction from Molecular Dynamics SimulationsWang J, Shi Y, Reiss K, Allen B, Maschietto F, Lolis E, Konigsberg WH, Lisi GP, Batista VS. Insights into Binding of Single-Stranded Viral RNA Template to the Replication–Transcription Complex of SARS-CoV‑2 for the Priming Reaction from Molecular Dynamics Simulations. Biochemistry 2022, 61: 424-432. PMID: 35199520, PMCID: PMC8887646, DOI: 10.1021/acs.biochem.1c00755.
- A Cysteine Variant at an Allosteric Site Alters MIF Dynamics and Biological Function in Homo- and Heterotrimeric AssembliesSkeens E, Pantouris G, Shah D, Manjula R, Ombrello MJ, Maluf NK, Bhandari V, Lisi GP, Lolis EJ. A Cysteine Variant at an Allosteric Site Alters MIF Dynamics and Biological Function in Homo- and Heterotrimeric Assemblies. Frontiers In Molecular Biosciences 2022, 9: 783669. PMID: 35252348, PMCID: PMC8893199, DOI: 10.3389/fmolb.2022.783669.
- Selective Recruitment of Lethal Pro-inflammatory Macrophages in Sepsis by MIF but not D-DT (MIF-2)Tilstam P, Schulte W, Holowka T, Kim B, Piecychna M, Pantouris G, Lolis E, Leng L, Bernhagen J, Bucala R. Selective Recruitment of Lethal Pro-inflammatory Macrophages in Sepsis by MIF but not D-DT (MIF-2). The Journal Of Immunology 2019, 202: 51.9-51.9. DOI: 10.4049/jimmunol.202.supp.51.9.
- Nanosecond Dynamics Regulate the MIF‐Induced Activity of CD74Pantouris G, Ho J, Shah D, Syed MA, Leng L, Bhandari V, Bucala R, Batista VS, Loria JP, Lolis E. Nanosecond Dynamics Regulate the MIF‐Induced Activity of CD74. Angewandte Chemie International Edition 2018, 57: 7116-7119. PMID: 29669180, PMCID: PMC6282165, DOI: 10.1002/anie.201803191.
- Nanosecond Dynamics Regulate the MIF‐Induced Activity of CD74Pantouris G, Ho J, Shah D, Syed M, Leng L, Bhandari V, Bucala R, Batista V, Loria J, Lolis E. Nanosecond Dynamics Regulate the MIF‐Induced Activity of CD74. Angewandte Chemie 2018, 130: 7234-7237. DOI: 10.1002/ange.201803191.
- Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions*Rajasekaran D, Gröning S, Schmitz C, Zierow S, Drucker N, Bakou M, Kohl K, Mertens A, Lue H, Weber C, Xiao A, Luker G, Kapurniotu A, Lolis E, Bernhagen J. Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions*. Journal Of Biological Chemistry 2016, 291: 15881-15895. PMID: 27226569, PMCID: PMC4957068, DOI: 10.1074/jbc.m116.717751.
- Structural BiologyHodsdon M, Lolis E. Structural Biology. 2015, 1-4. DOI: 10.1007/978-3-642-27841-9_5540-2.
- Characterization of PC2 Cterm Calcium-Binding Interaction and its Structural ImplicationsYang Y, Keeler C, Kuo I, Lolis E, Hodsdon M, Ehrlich B. Characterization of PC2 Cterm Calcium-Binding Interaction and its Structural Implications. Biophysical Journal 2015, 108: 215a. DOI: 10.1016/j.bpj.2014.11.1186.
- Structural BiologyHodsdon M, Lolis E. Structural Biology. 2015, 4384-4387. DOI: 10.1007/978-3-662-46875-3_5540.
- Structural Studies of Small Molecule Inhibitors of MIFCho Y, Lolis E. Structural Studies of Small Molecule Inhibitors of MIF. 2012, 101-118. DOI: 10.1142/9789814335362_0005.
- Structural BiologyHodsdon M, Lolis E. Structural Biology. 2011, 3549-3551. DOI: 10.1007/978-3-642-16483-5_5540.
- AV411 (Ibudilast) and AV1013 are non-competitive inhibitors of macrophage migration inhibitory factor: a novel induced-fit allosteric inhibition mechanism (133.11)Cho Y, Crichlow G, Vermeire J, Leng L, Du X, Hodsdon M, Bucala R, Cappello M, Gross M, Gaeta F, Johnson K, Lolis E. AV411 (Ibudilast) and AV1013 are non-competitive inhibitors of macrophage migration inhibitory factor: a novel induced-fit allosteric inhibition mechanism (133.11). The Journal Of Immunology 2010, 184: 133.11-133.11. DOI: 10.4049/jimmunol.184.supp.133.11.
- Structural BiologyHodsdon M, Lolis E. Structural Biology. 2009, 2849-2851. DOI: 10.1007/978-3-540-47648-1_5540.
- Structural Studies of MIFLolis E, Crichlow G. Structural Studies of MIF. 2007, 51-63. DOI: 10.1142/9789812775917_0004.
- The Structural Biology of ChemokinesLolis E, Murphy J. The Structural Biology of Chemokines. 2007, 9-30. DOI: 10.1007/978-1-59745-020-1_2.
- Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discoveryLolis E. Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery. Current Opinion In Pharmacology 2001, 1: 662-668. PMID: 11757824, DOI: 10.1016/s1471-4892(01)00112-6.
- Development of chronic colitis is dependent on the cytokine MIFde Jong Y, Abadia-Molina A, Satoskar A, Clarke K, Rietdijk S, Faubion W, Mizoguchi E, Metz C, Sahli M, ten Hove T, Keates A, Lubetsky J, Farrell R, Michetti P, van Deventer S, Lolis E, David J, Bhan A, Terhorst C. Development of chronic colitis is dependent on the cytokine MIF. Nature Immunology 2001, 2: 1061-1066. PMID: 11668338, DOI: 10.1038/ni720.
- CCR2 and CCR5 receptor‐binding properties of herpesvirus‐8 vMIP‐II based on sequence analysis and its solution structureShao W, Fernandez E, Sachpatzidis A, Wilken J, Thompson D, Schweitzer B, Lolis E. CCR2 and CCR5 receptor‐binding properties of herpesvirus‐8 vMIP‐II based on sequence analysis and its solution structure. The FEBS Journal 2001, 268: 2948-2959. PMID: 11358512, DOI: 10.1046/j.1432-1327.2001.02184.x.
- Comparison of the Structure of vMIP-II with Eotaxin-1, RANTES, and MCP-3 Suggests a Unique Mechanism for CCR3 Activation † , ‡Fernandez E, Wilken J, Thompson D, Peiper S, Lolis E. Comparison of the Structure of vMIP-II with Eotaxin-1, RANTES, and MCP-3 Suggests a Unique Mechanism for CCR3 Activation † , ‡. Biochemistry 2000, 39: 12837-12844. PMID: 11041848, DOI: 10.1021/bi001166f.
- Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytes.Sharron M, Pöhlmann S, Price K, Lolis E, Tsang M, Kirchhoff F, Doms R, Lee B. Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytes. Blood 2000, 96: 41-9. PMID: 10891428, DOI: 10.1182/blood.v96.1.41.013k53_41_49.
- Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytesSharron M, Pöhlmann S, Price K, Lolis E, Tsang M, Kirchhoff F, Doms R, Lee B. Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytes. Blood 2000, 96: 41-49. DOI: 10.1182/blood.v96.1.41.
- A cryocooling technique for protein crystals grown by dialysis from volatile solventsFernandez E, Joachimiak A, Lolis E. A cryocooling technique for protein crystals grown by dialysis from volatile solvents. Journal Of Applied Crystallography 2000, 33: 168-171. DOI: 10.1107/s0021889899012406.
- Crystallographic Studies of Phosphonate-Based α-Reaction Transition-State Analogues Complexed to Tryptophan Synthase † , ‡Sachpatzidis A, Dealwis C, Lubetsky J, Liang P, Anderson K, Lolis E. Crystallographic Studies of Phosphonate-Based α-Reaction Transition-State Analogues Complexed to Tryptophan Synthase † , ‡. Biochemistry 1999, 38: 12665-12674. PMID: 10504236, DOI: 10.1021/bi9907734.
- Pro-1 of Macrophage Migration Inhibitory Factor Functions as a Catalytic Base in the Phenylpyruvate Tautomerase Activity † , ‡Lubetsky J, Swope M, Dealwis C, Blake P, Lolis E. Pro-1 of Macrophage Migration Inhibitory Factor Functions as a Catalytic Base in the Phenylpyruvate Tautomerase Activity † , ‡. Biochemistry 1999, 38: 7346-7354. PMID: 10353846, DOI: 10.1021/bi990306m.
- Macrophage migration inhibitory factor: Cytokine, hormone, or enzyme?Swope M, Lolis E. Macrophage migration inhibitory factor: Cytokine, hormone, or enzyme? 1999, 139: 1-32. PMID: 10453691, DOI: 10.1007/bfb0033647.
- Accessibility of selenomethionine proteins by total chemical synthesis: structural studies of human herpesvirus‐8 MIP‐IIShao W, Fernandez E, Wilken J, Thompson D, Siani M, West J, Lolis E, Schweitzer B. Accessibility of selenomethionine proteins by total chemical synthesis: structural studies of human herpesvirus‐8 MIP‐II. FEBS Letters 1998, 441: 77-82. PMID: 9877169, DOI: 10.1016/s0014-5793(98)01520-8.
- Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factorSwope M, Sun H, Blake P, Lolis E. Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor. The EMBO Journal 1998, 17: 3534-3541. PMID: 9649424, PMCID: PMC1170690, DOI: 10.1093/emboj/17.13.3534.
- Crystal structure of chemically synthesized [N33A] stromal cell-derived factor 1α, a potent ligand for the HIV-1 “fusin” coreceptorDealwis C, Fernandez E, Thompson D, Simon R, Siani M, Lolis E. Crystal structure of chemically synthesized [N33A] stromal cell-derived factor 1α, a potent ligand for the HIV-1 “fusin” coreceptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 6941-6946. PMID: 9618518, PMCID: PMC22694, DOI: 10.1073/pnas.95.12.6941.
- Macrophage Migration Inhibitory Factor Interactions with Glutathione and S -Hexylglutathione*Swope M, Sun H, Klockow B, Blake P, Lolis E. Macrophage Migration Inhibitory Factor Interactions with Glutathione and S -Hexylglutathione*. Journal Of Biological Chemistry 1998, 273: 14877-14884. PMID: 9614090, DOI: 10.1074/jbc.273.24.14877.
- Solution Structure of Murine Macrophage Inflammatory Protein-2 † , ‡Shao W, Jerva L, West J, Lolis E, Schweitzer B. Solution Structure of Murine Macrophage Inflammatory Protein-2 † , ‡. Biochemistry 1998, 37: 8303-8313. PMID: 9622482, DOI: 10.1021/bi980112r.
- Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: Sequence analysis and mutagenesis identify receptor binding epitopesJerva L, Lolis E, Sullivan G. Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: Sequence analysis and mutagenesis identify receptor binding epitopes. Protein Science 1997, 6: 1643-1652. PMID: 9260277, PMCID: PMC2143775, DOI: 10.1002/pro.5560060805.
- The subunit structure of human macrophage migration inhibitory factor: evidence for a trimerSun H, Swope M, Craig C, Bedarkar S, Bernhagen J, Bucala R, Lolis E. The subunit structure of human macrophage migration inhibitory factor: evidence for a trimer. Protein Engineering Design And Selection 1996, 9: 631-635. PMID: 8875640, DOI: 10.1093/protein/9.8.631.
- Structure-Function Studies of Murine MIP-2, the Homologue of Melanoma Growth Stimulating Activity/gro-α and IL-8Lolis E, Jerva L. Structure-Function Studies of Murine MIP-2, the Homologue of Melanoma Growth Stimulating Activity/gro-α and IL-8. 1996, 183-194. DOI: 10.1007/978-3-642-61180-3_17.
- Model studies of the maillard reaction of Arg-Lys with D-riboseAl-Abed Y, Ulrich P, Kapurniotu A, Lolis E, Bucala R. Model studies of the maillard reaction of Arg-Lys with D-ribose. Bioorganic & Medicinal Chemistry Letters 1995, 5: 2929-2930. DOI: 10.1016/0960-894x(95)00513-s.
- Salvaging recombinants from low-efficiency ligase reactions for more efficient subcloning.Sun H, Lolis E. Salvaging recombinants from low-efficiency ligase reactions for more efficient subcloning. BioTechniques 1995, 18: 644-6, 648, 650. PMID: 7598899.
- Crystal structure of the K12M/G15A triosephosphate isomerase double mutant and electrostatic analysis of the active site.Joseph-McCarthy D, Lolis E, Komives E, Petsko G. Crystal structure of the K12M/G15A triosephosphate isomerase double mutant and electrostatic analysis of the active site. Biochemistry 1994, 33: 2815-23. PMID: 8130194, DOI: 10.1021/bi00176a010.
- Preliminary crystallographic analysis of murine macrophage inflammatory protein 2Lolis E, Sweet R, Cousens L, Tekamp-Olson P, Sherry B, Cerami A. Preliminary crystallographic analysis of murine macrophage inflammatory protein 2. Journal Of Molecular Biology 1992, 225: 913-915. PMID: 1602491, DOI: 10.1016/0022-2836(92)90411-c.
- Electrophilic catalysis in triosephosphate isomerase: the role of histidine-95.Komives E, Chang L, Lolis E, Tilton R, Petsko G, Knowles J. Electrophilic catalysis in triosephosphate isomerase: the role of histidine-95. Biochemistry 1991, 30: 3011-9. PMID: 2007138, DOI: 10.1021/bi00226a005.
- Structure of yeast triosephosphate isomerase at 1.9-A resolution.Lolis E, Alber T, Davenport R, Rose D, Hartman F, Petsko G. Structure of yeast triosephosphate isomerase at 1.9-A resolution. Biochemistry 1990, 29: 6609-18. PMID: 2204417, DOI: 10.1021/bi00480a009.
- Crystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5-A resolution: implications for catalysis.Lolis E, Petsko G. Crystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5-A resolution: implications for catalysis. Biochemistry 1990, 29: 6619-25. PMID: 2204418, DOI: 10.1021/bi00480a010.
- Transition-State Analogues in Protein Crystallography: Probes of the Structural Source of Enzyme CatalysisLolis E, Petsko G. Transition-State Analogues in Protein Crystallography: Probes of the Structural Source of Enzyme Catalysis. Annual Review Of Biochemistry 1990, 59: 597-630. PMID: 2197984, DOI: 10.1146/annurev.bi.59.070190.003121.
- Crystallography and site-directed mutagenesis of yeast triosephosphate isomerase: what can we learn about catalysis from a "simple" enzyme?Alber T, Davenport R, Giammona D, Lolis E, Petsko G, Ringe D. Crystallography and site-directed mutagenesis of yeast triosephosphate isomerase: what can we learn about catalysis from a "simple" enzyme? Cold Spring Harbor Symposia On Quantitative Biology 1987, 52: 603-13. PMID: 3331346, DOI: 10.1101/sqb.1987.052.01.069.
- Chiral discrimination in the covalent binding of bis(phenanthroline)dichlororuthenium(II) to B-DNABarton J, Lolis E. Chiral discrimination in the covalent binding of bis(phenanthroline)dichlororuthenium(II) to B-DNA. Journal Of The American Chemical Society 1985, 107: 708-709. DOI: 10.1021/ja00289a035.