Nikolaos Sgourakis

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Associate Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics

Contact information
9012 Colket Transalational Building
Civic Center Boulevard
Philadelphia, PA 19104
Office: 267-425-0110
undergrad (Ptychion in Biology)
National University of Athens, 2004.
M.Sc. (Bioinformatics)
National University of Athens, 2005.
Ph.D. (Dissertation in Molecular Biophysics)
Rensselaer Polytechnic Institute, 2009.
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Description of Research Expertise

Research Interests
My 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.

Antigen Processing and Presentation; Immuno-oncology; T cell Immune Responses; Immune Evasion Mechanisms; Cytokine Engineering; Synthetic Biology; Protein Dynamics; Nuclear Magnetic Resonance Spectroscopy; Computational Structural Biology; Machine Learning

Research Details
The Sgourakis Lab investigates the processes that enable adaptive immune responses against infectious diseases and cancer. Our lab's principal efforts focus on mechanistic, structural and functional studies of protein complexes, with emphasis on the development of an iterative experimental / computational approach. To gain an atomic-detail description of these processes and to characterize novel therapeutic targets, we integrate cutting-edge structural biology methods from Nuclear Magnetic Resonance Spectroscopy, complementary biophysical and biochemical techniques, computational modeling and functional immunoassays. Our efforts are done in close collaboration with several groups within the vibrant immunology and immuno-oncology communities at Children's Hospital of Philadelphia and the University of Pennsylvania.

The class-I and class-II proteins of the Major Histocompatibility Complex play an essential role in immune surveillance, by displaying epitopic peptides derived from the processing of aberrant proteins on the cell surface, where they can be recognized through interactions with specialized receptors on T cells and Natural Killer cells. In recent work, our team found that the dynamic plasticity of MHC-I proteins, occurring over a range of timescales from microseconds to milliseconds, plays an essential role in their peptide selector function though the sampling of minor, “excited-state” conformations. Our detailed biophysical characterization of the molecular chaperone TAPBPR provided us with a high-resolution view of peptide exchange on MHC-I proteins and led to the development a high-throughput methodology for generating barcoded MHC tetramer libraries encompassing hundreds of unique antigen specificities.

Selected Publications

Wei Kathy Y, Moschidi Danai, Bick Matthew J, Nerli Santrupti, McShan Andrew C, Carter Lauren P, Huang Po-Ssu, Fletcher Daniel A, Sgourakis Nikolaos G, Boyken Scott E, Baker David: Computational design of closely related proteins that adopt two well-defined but structurally divergent folds. Proceedings of the National Academy of Sciences of the United States of America 117(13): 7208-7215, Mar 2020.

De Paula Viviane S, Jude Kevin M, Nerli Santrupti, Glassman Caleb R, Garcia K Christopher, Sgourakis Nikolaos G: Interleukin-2 druggability is modulated by global conformational transitions controlled by a helical capping switch. Proceedings of the National Academy of Sciences of the United States of America 117(13): 7183-7192, Mar 2020.

Park Jooyoung, Selvaraj Brinda, McShan Andrew C, Boyken Scott E, Wei Kathy Y, Oberdorfer Gustav, DeGrado William, Sgourakis Nikolaos G, Cuneo Matthew J, Myles Dean Aa, Baker David: De novo design of a homo-trimeric amantadine-binding protein. eLife 8, 12 2019.

McShan Andrew C, Devlin Christine A, Overall Sarah A, Park Jihye, Toor Jugmohit S, Moschidi Danai, Flores-Solis David, Choi Hannah, Tripathi Sarvind, Procko Erik, Sgourakis Nikolaos G: Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection. Proceedings of the National Academy of Sciences of the United States of America 116(51): 25602-25613, 12 2019.

Marceau Aimee H, Brison Caileen M, Nerli Santrupti, Arsenault Heather E, McShan Andrew C, Chen Eefei, Lee Hsiau-Wei, Benanti Jennifer A, Sgourakis Nikolaos G, Rubin Seth M: An order-to-disorder structural switch activates the FoxM1 transcription factor. eLife 8, 05 2019.

De Paula Viviane S, Sgourakis Nikolaos G, Francischetti Ivo M B, Almeida Fabio C L, Monteiro Robson Q, Valente Ana Paula: NMR structure determination of Ixolaris and factor X(a) interaction reveals a noncanonical mechanism of Kunitz inhibition. Blood 134(8): 699-708, 08 2019.

Nerli Santrupti, Sgourakis Nikolaos G: CS-ROSETTA. Methods in enzymology 614: 321-362, 2019.

Chen Zibo, Boyken Scott E, Jia Mengxuan, Busch Florian, Flores-Solis David, Bick Matthew J, Lu Peilong, VanAernum Zachary L, Sahasrabuddhe Aniruddha, Langan Robert A, Bermeo Sherry, Brunette T J, Mulligan Vikram Khipple, Carter Lauren P, DiMaio Frank, Sgourakis Nikolaos G, Wysocki Vicki H, Baker David: Programmable design of orthogonal protein heterodimers. Nature 565(7737): 106-111, 01 2019.

Nerli Santrupti, McShan Andrew C, Sgourakis Nikolaos G: Chemical shift-based methods in NMR structure determination. Progress in nuclear magnetic resonance spectroscopy 106-107: 1-25, Jun - Aug 2018.

Marcos Enrique, Chidyausiku Tamuka M, McShan Andrew C, Evangelidis Thomas, Nerli Santrupti, Carter Lauren, Nivón Lucas G, Davis Audrey, Oberdorfer Gustav, Tripsianes Konstantinos, Sgourakis Nikolaos G, Baker David: De novo design of a non-local β-sheet protein with high stability and accuracy. Nature structural & molecular biology 25(11): 1028-1034, 11 2018.

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Last updated: 02/14/2022
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