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Nikolaos G. Sgourakis, PhD
Nikolaos G. Sgourakis
Principal Investigator

Dr. Sgourakis’ research focuses on understanding the intricate molecular mechanisms that determine the vast repertoire of peptide antigens displayed by the proteins of the Major Histocompatibility Complex for immune surveillance by T cells and Natural Killer cells.

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Bio

Dr. Sgourakis is a recognized expert in Major Histocompatibility Complex (MHC)-I structure, function and mechanism. He is the inventor of a powerful high-throughput platform used to identify and analyze antigen repertoires relevant in immuno-oncology and immunotherapy.

His team investigate the dynamic properties of pleiotropic cytokines, with the aim to design conformation-selective protein therapeutics to treat autoimmunity and cancer, overcoming the deficiencies of current drugs and antibody-based therapies. They integrate cutting-edge structural biology tools from Nuclear Magnetic Resonance Spectroscopy with computational protein structure modeling and design, and functional immunoassays.

Dr. Sgourakis is an associate professor in the Center for Computational & Genomic Medicine at Children’s Hospital of Philadelphia, and the Department of Biochemistry and Biophysics at the University of Pennsylvania.

Prior to this, he was an assistant professor of Chemistry and Biochemistry at the University of California since 2015, where he led studies of immune system proteins implicated in infectious diseases and cancer.

From 2013 to 2015, he was Intramural Research Fellow at the National Institute of Diabetes and Digestive and Kidney Diseases, focusing on Nuclear Magnetic Resonance (NMR) spectroscopy studies of virus/host protein interaction networks involved in immune evasion, and the establishment of latency. During his postdoctoral work at the University of Washington, he developed computational methods for modelling the structures of protein complexes by integrating NMR with cryoelectron microscopy data.

Dr. Sgourakis earned his PhD from Rensselaer Polytechnic Institute in 2009, and his Master’s degree in Bioinformatics from the National University of Athens. As an undergraduate student, he developed machine learning algorithms for predicting properties of G-protein coupled receptors currently used in pharmacology and drug discovery.

Education and Training

PhD, Biology, Rensselaer Polytechnic Institute, 2009

MSc, Bioinformatics, University of Athens, 2005

Ptychion, Biology, University of Athens, 2004

Titles and Academic Titles

Associate Professor in the Center for Computational and Genomic Medicine at Children’s Hospital of Philadelphia

Department of Biochemistry and Biophysics at the University of Pennsylvania

Publication Highlights

Overall SA, Toor JS, Hao S, Yarmarkovich M, Nguyen S, Japp AS, Moschidi D, Betts MR, Maris JM, Smibert P, Sgourakis NG. High throughput pMHC-I tetramer library production using chaperone-mediated peptide exchange. Nature Communications. 2020 Apr; 11:1909 PMID: 32312993
De Paula VS, Jude KM, Nerli S, Glassman CR, Garcia KC, Sgourakis NG. Interleukin-2 druggability is modulated by global conformational transitions controlled by a helical capping switch. Proc Natl Acad Sci USA. 2020 Mar; 117(13):7183-7192. PMID: 32184322
McShan AC, Devlin C, Overall SA, Park J, Toor JS, Moschidi D, Flores-Solis D, Choi H, Tripathi S, Procko E, Sgourakis NG. Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection. Proc Natl Acad Sci USA. 2019 Dec; 116 (51) 25602-25613. PMID: 31796585
McShan AC, Natarajan K, Kumirov K, Flores-Solis D, Jiang J, Badstubner M, Toor JS, Bagshaw CR, Kovrigin EL, Margulies DH, Sgourakis NG. Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle. Nature Chemical Biology. 2018 Jul; 14(8):811-820. PMID: 29988068
Toor JS, Rao AA, McShan AC, Yarmarkovich M, Nerli S, Yamaguchi K, Madejska AA, Nguyen S, Tripathi S, Maris JM, Salama SR, Haussler D, Sgourakis NG. A recurrent mutation in anaplastic lymphoma kinase with distinct neoepitope conformations. Frontiers in Immunology. 2018 Jan; 9:99. PMID: 29441070