Biochemical basis of nervous system development, protein-protein interaction, strutural biology of extracellular proteins
1999 Bilkent University, Ankara, Turkey B.S. 06/99
2006 U of Texas Southwestern Medical Center at Dallas Ph.D. 5/06
2013 Stanford University Postdoctoral 6/13
2014-present Assistant Professor, Department of Biochemistry and Molecular Biology, The University of Chicago
Our laboratory is working on understanding how specific cellular connections are made within complex, multi-cellular organisms. Our approach is molecular: We are, first, working on discovering protein-protein complexes that are likely to drive specificity and function of cellular adhesions, using high-throughput approaches. Then, we take a structural approach to elucidate how such complexes work, through biophysics and x-ray crystallography, in collaboration with model-organism geneticists. We are especially interested in molecular cues and “identification tags” that determine the wiring networks in the nervous system.
In the long term, we are hoping to make an impact in several fields: We will significantly contribute to revealing the “Extracellular Interactome”, a large section of the map of protein-protein interactions. We are actively working to identify and characterize cell surface receptors that partake in axonal guidance and pruning, synaptogenesis, and synaptic function. Finally, we are trying to understand the molecular “rules” of how protein-protein complexes can create cellular adhesions.
Özkan E, Chia PH, Wang RR, Goriatcheva N, Borek D, Otwinowski Z, Walz T, Shen K, Garcia KC. Extracellular architecture of the SYG-1/SYG-2 adhesion complex instructs synaptogenesis. Cell. 2014 Jan 30;156(3):482-94.
Birnbaum ME, Mendoza JL, Sethi DK, Dong S, Glanville J, Dobbins J, Özkan E, Davis MM, Wucherpfennig KW, Garcia KC. Deconstructing the peptide-MHC specificity of T cell recognition. Cell. 2014 May 22;157(5):1073-87.
Weiskopf K, Ring AM, Ho CC, Volkmer JP, Levin AM, Volkmer AK, Özkan E, Fernhoff NB, van de Rijn M, Weissman IL, Garcia KC. Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies. Science. 2013 Jul 5;341(6141):88-91.
Özkan E, Carrillo RA, Eastman CL, Weiszmann R, Waghray D, Johnson KG, Zinn K, Celniker SE, Garcia KC. An extracellular interactome of immunoglobulin and LRR proteins reveals receptor-ligand networks. Cell. 2013 Jul 3;154(1):228-39.
Yu XM, Gutman I, Mosca TJ, Iram T, Özkan E, Garcia KC, Luo L, Schuldiner O. Plum, an immunoglobulin superfamily protein, regulates axon pruning by facilitating TGF-β signaling. Neuron. 2013 May 8;78(3):456-68.
Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Özkan E, Leonard WJ, Garcia KC. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Nat Immunol. 2012 Dec;13(12):1187-95.
Feng D, Kim T, Özkan E, Light M, Torkin R, Teng KK, Hempstead BL, Garcia KC. Molecular and structural insight into proNGF engagement of p75NTR and sortilin. J Mol Biol. 2010 Mar 5;396(4):967-84.
Eroglu C, Allen NJ, Susman MW, O'Rourke NA, Park CY, Özkan E, Chakraborty C, Mulinyawe SB, Annis DS, Huberman AD, Green EM, Lawler J, Dolmetsch R, Garcia KC, Smith SJ, Luo ZD, Rosenthal A, Mosher DF, Barres BA. Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell. 2009 Oct 16;139(2):380-92.
Araç D, Boucard AA, Özkan E, Strop P, Newell E, Südhof TC, Brunger AT. Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca2+ interactions. Neuron. 2007 Dec 20;56(6):992-1003.
Özkan E, Yu H, Deisenhofer J. Mechanistic insight into the allosteric activation of a ubiquitin-conjugating enzyme by RING-type ubiquitin ligases. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18890-5.
Tang Z, Li B, Bharadwaj R, Zhu H, Özkan E, Hakala K, Deisenhofer J, Yu H. APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Mol Biol Cell. 2001 Dec;12(12):3839-51.
Usher KC, Özkan E, Gardner KH, Deisenhofer J. The plug domain of FepA, a TonB-dependent transport protein from Escherichia coli, binds its siderophore in the absence of the transmembrane barrel domain. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10676-81.