Georgiou Lab

About The Georgiou Lab

Since 2009 the Georgiou laboratory has been focused on the discovery and development of protein therapeutics and on the analysis of adaptive immune responses.   Current projects include:

• Engineering and preclinical/clinical development of human enzyme therapeutics for the treatment of solid tumors and leukemias.

• Development of methods for the molecular-level identification of the human antibody repertoire in blood and in secretions.

• Analysis of the antibody repertoire elicited by viral infection (e.g. HIV-1) and vaccination to aid the development of more efficient vaccination stategies.

• Engineering of antibody therapeutics displaying enhanced ability to recruit cytotoxic leukocytes and blood proteins (complement) for the effective clearance of pathogens.

2023 Research

• Goike J, Hsieh CL, Horton AP, Gardner EC, Zhou L, Bartzoka F, Wang N, Javanmardi K, Herbert A, Abbassi S, Xie X, Xia H, Shi PY, Renberg R, Segall- Shapiro TH, Terrace CI, Wu W, Shroff R, Byrom M, Ellington AD, Marcotte EM, Musser JM, Kuchipudi SV, Kapur V, Georgiou G, Weaver SC, Dye JM, Boutz DR, McLellan JS, Gollihar JD. SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode. Commun Biol. 2023 Dec 11;6(1):1250. PMID: 38082099; PMCID: PMC10713552.

• Lee K, Park J, Tanno H, Georgiou G, Diamond B, Kim SJ. Peripheral T cell activation, not thymic selection, expands the T follicular helper repertoire in a lupus-prone murine model. Proc Natl Acad Sci U S A. 2023 Nov 28;120(48):e2309780120. Epub 2023 Nov 20. PMID: 37983487; PMCID: PMC10691248.

• Weber T, Dähling S, Rose S, Affeldt P, Vanshylla K, Ullrich L, Gieselmann L, Teipel F, Gruell H, Di Cristanziano V, Kim DS, Georgiou G, Koch M, Kreer C, Klein F. Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool. Sci Immunol. 2023 Nov 17;8(89):eadk5845. Epub 2023 Nov 17. PMID: 37976348.

• Schommers P, Kim DS, Schlotz M, Kreer C, Eggeling R, Hake A, Stecher M, Park J, Radford CE, Dingens AS, Ercanoglu MS, Gruell H, Odidika S, Dahlhaus M, Gieselmann L, Ahmadov E, Lawong RY, Heger E, Knops E, Wyen C, Kümmerle T, Römer K, Scholten S, Wolf T, Stephan C, Suárez I, Raju N, Adhikari A, Esser S, Streeck H, Duerr R, Nanfack AJ, Zolla-Pazner S, Geldmacher C, Geisenberger O, Kroidl A, William W, Maganga L, Ntinginya NE, Georgiev IS, Vehreschild JJ, Hoelscher M, Fätkenheuer G, Lavinder JJ, Bloom JD, Seaman MS, Lehmann C, Pfeifer N, Georgiou G, Klein F. Dynamics and durability of HIV-1 neutralization are determined by viral replication. Nat Med. 2023 Nov;29(11):2763-2774. Epub 2023 Nov 13. PMID: 37957379; PMCID: PMC10667105.

• Gjuka D, Adib E, Garrison K, Chen J, Zhang Y, Li W, Boutz D, Lamb C, Tanno Y, Nassar A, El Zarif T, Kale N, Rakaee M, Mouhieddine TH, Alaiwi SA, Gusev A, Rogers T, Gao J, Georgiou G, Kwiatkowski DJ, Stone E. Enzyme-mediated depletion of methylthioadenosine restores T cell function in MTAP-deficient tumors and reverses immunotherapy resistance. Cancer Cell. 2023 Oct 9;41(10):1774-1787.e9. Epub 2023 Sep 28. PMID: 37774699; PMCID: PMC10591910.

• Wilder CS, Chiou J, Battenhouse A, Saha A, Chen Z, Kim E, Gadallah MI, Tiziani S, Georgiou G, Stone E, DiGiovanni J. Enzymatic depletion of l-Met using an engineered human enzyme as a novel therapeutic strategy for melanoma. Mol Carcinog. 2023 Jun 28. Epub ahead of print. PMID: 37378415.

• Saha A, Zhao S, Kindall A, Wilder C, Friedman CA, Clark R, Georgiou G, Stone E, Kidane D, DiGiovanni J. Cysteine depletion sensitizes prostate cancer cells to agents that enhance DNA damage and to immune checkpoint inhibition. J Exp Clin Cancer Res. 2023 May 11;42(1):119. PMID: 37170264; PMCID: PMC10173527.

2022 Research

• Kuraoka M, Curtis NC, Watanabe A, Tanno H, Shin S, Ye K, Macdonald E, Lavidor O, Kong S, Von Holle T, Windsor I, Ippolito GC, Georgiou G, Walter EB, Kelsoe G, Harrison SC, Moody MA, Bajic G, Lee J. Infant Antibody Repertoires during the First Two Years of Influenza Vaccination. mBio. 2022 Oct 31:e0254622. Epub ahead of print. PMID: 36314798.

• Blazeck J, Karamitros CS, Ford K, Somody C, Qerqez A, Murray K, Burkholder NT, Marshall N, Sivakumar A, Lu WC, Tan B, Lamb C, Tanno Y, Siddiqui MY, Ashoura N, Coma S, Zhang XM, McGovern K, Kumada Y, Zhang YJ, Manfredi M, Johnson KA, D'Arcy S, Stone E, Georgiou G. Bypassing evolutionary dead ends and switching the rate-limiting step of a human immunotherapeutic enzyme. Nat Catal. 2022 Oct;5(10):952-967.  Epub 2022 Oct 19. PMID: 36465553; PMCID: PMC9717613.

• Zhang L, Hobeika CS, Khabibullin D, Yu D, Filippakis H, Alchoueiry M, Tang Y, Lam HC, Tsvetkov P, Georgiou G, Lamb C, Stone E, Puigserver P, Priolo C, Henske EP. Hypersensitivity to ferroptosis in chromophobe RCC is mediated by a glutathione metabolic dependency and cystine import via solute carrier family 7 member 11. Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2122840119. Epub 2022 Jul 8. PMID: 35867762.

• Pataskar A, Champagne J, Nagel R, Kenski J, Laos M, Michaux J, Pak HS, Bleijerveld OB, Mordente K, Navarro JM, Blommaert N, Nielsen MM, Lovecchio D, Stone E, Georgiou G, de Gooijer MC, van Tellingen O, Altelaar M, Joosten RP, Perrakis A, Olweus J, Bassani-Sternberg M, Peeper DS, Agami R. Author Correction: Tryptophan depletion results in tryptophan-to-phenylalanine substitutants. Nature. 2022 Aug;608(7922):E20. Erratum for: Nature. 2022 Mar;603(7902):721-727. PMID: 35840685; PMCID: PMC9365688.

• Karamitros CS, Murray K, Winemiller B, Lamb C, Stone EM, D'Arcy S, Johnson KA, Georgiou G. Leveraging intrinsic flexibility to engineer enhanced enzyme catalytic activity. Proc Natl Acad Sci U S A. 2022 Jun 7;119(23):e2118979119. Epub 2022 Jun 3. PMID: 35658075; PMCID: PMC9191678.

• G Delidakis, JE Kim, K George, G Georgiou. Improving Antibody Therapeutics by Manipulating the Fc Domain: Immunological and Structural Considerations. Annual Review of Biomedical Engineering 24. April 1, 2022.

• A Pataskar, J Champagne, R Nagel, J Kenski, M Laos, J Michaux, HS Pak, ...G Georgiou. Tryptophan depletion results in tryptophan-to-phenylalanine substitutants. Nature 603 (7902), 721-727. March 8, 2022.

2021 Research

• W Charab, MG Rosenberger, H Shivram, JM Mirazee, M Donkor, SR Shekhar, D Gjuka, KH Khoo, JE Kim, VR Iyer, G Georgiou. IgG Immune Complexes Inhibit Naïve T Cell Proliferation and Suppress Effector Function in Cytotoxic T Cells. Frontiers in immunology. August 10, 2021.

• J Jung, ST Mundle, IV Ustyugova, AP Horton, DR Boutz, S Pougatcheva, P Prabakaran, JR McDaniel, GR King, D Park, MD Person, C Ye, B Tan, Y Tanno, JE Kim, NC Curtis, J DiNapoli, S Delagrave, TM Ross, GC Ippolito, H Kleanthous, J Lee, G Georgiou. Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans. J Clin Invest  131(13):e148763.  PMID: 34196304; PMCID: PMC8245176. July 1, 2021.

• KR McCarthy, J Lee, A Watanabe, M Kuraoka, L-R Robinson-McCarthy, G Georgiou, G Kelsoe, SC Harrison. A Prevalent Focused Human Antibody Response to the Influenza Hemagglutinin Head Interface, mBio in press. June 1, 2021.

• WN Voss, YJ Hou, NV Johnson, G Delidakis, JE Kim, K Javanmardi, AP Horton, F Bartzoka, CJ Paresi, Y Tanno, C-W Chou, SA Abbasi, W Pickens, K George, DR Boutz, DM Towers, JR McDaniel, D Billick, J Goike, L Rowe, D Batra, J Pohl, J Lee, S Gangappa, S Sambhara, M Gadush, N Wang, MD Person, BL Iverson, JD Gollihar, J Dye, A Herbert, IJ Finkelstein, RS Baric, JS McLellan, G Georgiou, JJ* Lavinder, GC* Ippolito. Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes. Science  372(6546):1108-1112. PMID: 33947773. May 4, 2021.

• JD Gollihar, JS McLellan, DR Boutz, J Goike, A Horton, EC Gardner, F Bartzoka, N Wang, K Javanmardi, A Herbert, S Abbasi, R Renberg, MJ Johanson, JA Cardona, T Segall-Shapiro, L Zhou, RH Nissly, A Gontu, M Byrom, AC Maranhao, AM Battenhouse, V Gejji, L Soto-Sierra, ER Foster, SL Woodard, ZL Nikolov, J Lavinder, WN Voss, A Annapareddy, GC Ippolito, AD Ellington, EM Marcotte, IJ Finkelstein, RA Hughes, JM Musser, SV Kuchipudi, V Kapur, G Georgiou, JM Dye. Synthetic repertoires derived from convalescent COVID-19 patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality. bioRxiv. April 9, 2021.

• CA Denard, C Paresi, R Yaghi, N McGinnis, Z Bennett, L Yi, G Georgiou, BL Iverson. YESS 2.0, a Tunable Platform for Enzyme Evolution, Yields Highly Active TEV Protease Variants. ACS Synthetic Biology. Jan 5, 2021.

2020 Research

• R Verardi, LC Lindesmith, Y Tsybovsky, J Gorman, Y-G Chuang, K Edwards, PB Jensen, ML Mallory, L Ou, A Schön, ES Tully, G Georgiou, RS Baric, PD Kwong. Disulfide-Stabilization of Human Norovirus GI.1 Virus-like Particles Focuses Immune Response Toward Neutralizing Epitopes NPJ Vaccines (2020) in press. December 14, 2020.

• CS Karamitros, K Murray, Y Sugiyama, Y Kumada, KA Johnson, G Georgiou, S D’Arcy, EM Stone. Conformational Dynamics Contribute to Substrate Selectivity and Catalysis in Human Kynureninase. ACS Chemical Biology, December 4, 2020.

• TH Kang, C-H Lee, G Delidakis, J Jung, O Richard-Le Goff, J Lee, JE Kim, W Charab, P Bruhns, G Georgiou. An Engineered Human Fc variant With Exquisite Selectivity for FcγRIIIa FcγRIIIa V158 Mediates Reveals Potent That Antibody Ligation of Dependent Cellular Phagocytosis With GM … Roles of Fc Receptors in Disease and Therapy. July 22, 2020.

• MR Mehaffey, J Lee, J Jung, MB Lanzillotti, EE Escobar, KR Morgenstern, G Georgiou, JS Brodbelt, Mapping a Conformational Epitope of Hemagglutinin A Using Native Mass Spectrometry and Ultraviolet Photodissociation, Anal Chem 92(17):11869-11878 (2020) PMID: 32867493. July 17, 2020.

• N Ashoura, J Dekker, TA Triplett, K Garrison, J Blazeck, C Karamitros, C Lamb, Y Tanno, LIR Ehrlich, M Zhang, MG Manfredi, E Stone, G Georgiou. The Force Awakens: Illuminating the Role of Kynurenine in Cancer Progression and Treatment. The Journal of Immunology. May 1, 2020.

• H Tanno, J McDaniel, C Stevens, W Voss, J Li, R Durrett, J Lee, J Gollihar, Y Tanno, G Delidakis, A Pothukuchy, J Ellefson, J Goronzy, J Maynard, A Ellington, G Ippolito, G Georgiou. One step ultra-high-throughput sequencing of the paired antibody VH: VL and TCRβ: α repertoires using cell lysate resistant xenopolymerase in emulsion. The Journal of Immunology. May 1, 2020.