Nikolaos Sgourakis
Associate Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics
Graduate Group Affiliations
Contact information
CHOP
9012 Colket Transalational Building
Civic Center Boulevard
Philadelphia, PA 19104
9012 Colket Transalational Building
Civic Center Boulevard
Philadelphia, PA 19104
Office: 267-425-0110
Publications
Education:
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.
Permanent linkundergrad (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.
Description of Research Expertise
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. During my training, done in consecutive postdoctoral appointments at the University of Washington and at the NIH, I synthesized concepts and methods from protein structure modeling and design with NMR spectroscopy, to address challenging systems of significant dynamic complexity.With these tools in hand, I have developed an independent program aiming to tackle contemporary problems in molecular immunology. 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.
Research in my lab has been continuously supported by the NIH for the past 8 years, and we have published over 50 articles in leading peer-reviewed journals. Supported by an NIGMS Early Career MIRA award and an R01 award from NIAID, my group has delivered foundational, mechanistic studies of key biomolecules involved in immune recognition, and targeted cancer therapy.
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.
Selected Publications
McShan A.C., Flores-Solis D., Sun Y., Garfinkle S., Young M.C., Toor J., Sgourakis N.G. : Conformational plasticity of RAS Q61 family of neoepitopes results in distinct features for targeted recognition Nature Communications 14, December 2023.Sun Y., Florio T.J., Gupta S., Young M.C., Marshall Q.F., Garfinkle S.E., Papadaki G.F., Truong H.V., Mycek E., Li P., Farrel A., Church N.L., Jabar S., Beasley M.D., Kiefel B.R., Yarmarkovich M., Mallik L., Maris J.M., Sgourakis N.G.: Structural principles of peptide-centric Chimeric Antigen Receptor recognition guide ther- apeutic expansion Science Immunology 8, December 2023.
Yarmarkovich M, Marshall QF, Warrington JM, Premaratne R, Farrel A, Groff D, Li W, di Marco M, Runbeck E, Truong H, Toor JS, Tripathi S, Nguyen S, Shen H, Noel T, Church NL, Weiner A, Kendsersky N, Martinez D, Weisberg R, Christie M, Eisenlohr L, Bosse KR, Dimitrov DS, Stevanovic S, Sgourakis NG, Kiefel BR, Maris JM.: Targeting of intracellular oncoproteins with peptide-centric CARs. Nature 623: 820-827, November 2023.
Gupta S., Nerli S., Kutti Kandi S., Merski G.L., Sgourakis N.G.: HLA3DB: comprehensive annotation of peptide/HLA complexes enables blind structure prediction of T cell epitopes Nature Communications 14(1), October 2023.
Papadaki G.F., Woodward C.H., Young M.C., Winters T.J., Burslem G.M., Sgourakis N.G.: A Chicken Tapasin ortholog can chaperone empty HLA-B37:01 molecules independent of other peptide-loading components Journal of Biological Chemistry 299(10), October 2023.
Sun Y., Young M.C., Woodward C.H., Danon J.N., Truong H.V., Gupta S., Winters T.J., Font-Burgada J. Burslem G.M., Sgourakis N.G.: Universal open MHC-I molecules for rapid peptide loading and enhanced complex stability across HLA allotypes Proc Natl Acad Sci U S A 120(25), June 2023.
Sun Y., Papadaki G.F., Devlin C.A., Young M.C., Woodward C.H., Danon J.N., Truong H.V., Gupta S., Winters T.J., Burslem G.M., Procko E., Sgourakis N.G.: Xeno interactions between MHC-I proteins and molecular chaperones enable ligand ex- change on a broad repertoire of HLA allotypes Science Advances 9, February 2023.
Papadaki G.F., Ani O., Florio T.J., Young M.C., Danon J.N., Sun Y., Dersh D., Sgourakis N.G.: Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules Frontiers in Immunology 14, January 2023.
Hu K., Lee W., Montelione G.T., Sgourakis N.G., Vogeli B.: Computational approaches for interpreting experimental data and understanding protein structure, dynamics and function relationships Frontiers in Molecular Biosciences 9, October 2022.
Jiang J., Taylor D.K., Kim E.J., Boyd L.F., Ahmad J., Mage M.G., Truong H.V., Wood- ward C.H., Sgourakis N.G., Cresswell P., Margulies D.H., Natarajan K.: Structural mechanism of tapasin-mediated MHC-I peptide loading in antigen presentation Nature Communications 13, September 2022.