About

Engin Ozkan, PhD, is an Associate Professor of Biochemistry and Molecular Biology and Neuroscience at the University of Chicago. His research focuses on the biochemistry, signaling activity, and interaction networks of proteins essential for nervous system development and function. His laboratory investigates how cell surface receptors and secreted protein ligands determine cellular connectivity, which drives the development of complex systems and organs in multicellular organisms. The lab employs a multidisciplinary approach, including crystallography, cellular signaling assays, protein engineering, and genetic modifications in model organisms, to decipher protein-protein interaction networks involved in axon guidance, pruning, and synapse formation. Dr. Ozkan's academic background includes a PhD in Molecular Biophysics from the University of Texas Southwestern Medical Center, a postdoctoral fellowship in Biochemistry at Stanford University, and a B.S. in Molecular Biology & Genetics from Bilkent University in Turkey. His contributions to neuroscience and biochemistry have been recognized through fellowships such as the Alfred P. Sloan Research Fellowship in Neuroscience and the Klingenstein-Simons Neuroscience Fellowship. He is actively involved in graduate programs related to Biochemistry & Molecular Biophysics, Neurobiology, and PhD programs in Neurobiology at the University of Chicago.

Research topics

• Biology
• Neuroscience
• Cell biology
• Genetics
• Biophysics
• Biochemistry

Selected publications

• Author Correction: Repulsions instruct synaptic partner matching in an olfactory circuit

  Nature · 2026-01-04

  articleOpen access
  PublisherOA PDFDOI

• Reciprocal repulsions enforce heterotypic dendrite segregation in an olfactory circuit

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-27

  articleOpen access

  Summary How dendrites of different neurons segregate into discrete spatial domains during neural circuit assembly is poorly understood. Here, using the Drosophila olfactory system, we found that heterophilic interactions between two cell-surface proteins Teneurin-m (Ten-m) and Capricious (Caps) drive dendrite segregation. Ten-m and Caps are expressed in largely inverse patterns across projection neuron (PN) types when PNs are establishing their dendritic territories. Loss of Ten-m in Ten-m + PNs causes their dendrites to invade Caps + territories, whereas loss of Caps in Caps + PNs causes dendrite invasion into Ten-m + territories. Structure-guided mutations that abolish Ten-m–Caps binding disrupt dendrite segregation, whereas the same mutation on Ten-m preserves its homophilic attraction in a synaptic partner matching assay. These results support a model in which mutual repulsion between two inversely expressed cell-surface proteins drive dendrite segregation into discrete glomerular territories.

  PublisherOA PDFDOI

• Repulsions instruct synaptic partner matching in an olfactory circuit

  Nature · 2025-11-19 · 1 citations

  articleOpen access

  Abstract Neurons exhibit extraordinary precision in selecting synaptic partners. Although cell-surface proteins (CSPs) that mediate attractive interactions between developing axons and dendrites have been shown to instruct synaptic partner matching 1,2 , the degree to which repulsive interactions have a role is less clear. Here, using a genetic screen guided by single-cell transcriptomes 3,4 , we identified three CSP pairs, Toll2–Ptp10D, Fili–Kek1 and Hbs/Sns–Kirre, that mediate repulsive interactions between non-partner olfactory receptor neuron (ORN) axons and projection neuron (PN) dendrites in the developing Drosophila olfactory circuit. Each CSP pair exhibits inverse expression patterns in the select ORN–PN partners. Loss of each CSP in ORNs led to similar synaptic partner matching deficits as the loss of its partner CSP in PNs, and mistargeting phenotypes caused by overexpressing one CSP could be suppressed by loss of its partner CSP. All CSP pairs are also differentially expressed in other brain regions. Together, our data reveal that multiple repulsive CSP pairs work together to ensure precise synaptic partner matching during development by preventing neurons from forming connections with non-cognate partners.

  PublisherDOI

• A dendritic guidance receptor functions in both ligand dependent and independent modes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-12

  preprintOpen access

  Abstract The formation of an appropriately shaped dendritic arbor is critical for a neuron to receive information. Dendritic morphogenesis is a dynamic process involving growth, branching, and retraction. How the growth and stabilization of dendrites are coordinated at the molecular level remains a key question in developmental neurobiology. The highly arborized and stereotyped dendritic arbors of the Caenorhabditis elegans PVD neuron are shaped by the transmembrane DMA-1 receptor through its interaction with a tripartite ligand complex consisting of SAX-7, MNR-1, and LECT-2. However, receptor null mutants exhibit strongly reduced dendrite outgrowth, whereas ligand null mutants show disordered branch patterns, suggesting a ligand-independent function of the receptor. To test this idea, we identified point mutations in dma-1 that disrupt receptor-ligand binding and introduced corresponding mutations into the endogenous gene. We show that the ligand-free receptor is sufficient to drive robust, disordered dendritic branch formation but results in a complete loss of arbor shape. This disordered outgrowth program utilizes similar downstream effectors as the stereotyped outgrowth program, further arguing that ligand binding is not necessary for outgrowth. Finally, we demonstrate that ligand binding is required to maintain higher-order dendrites after development is complete. Taken together, our findings support a surprising model in which ligand-free and ligand-bound DMA-1 receptors have distinct functions: the ligand-free receptor promotes stochastic outgrowth and branching, whereas the ligand-bound receptor guides stereotyped dendrite morphology by stabilizing arbors at target locations.

  PublisherDOI

• A dendritic guidance receptor functions in both ligand dependent and independent modes

  PLoS Genetics · 2025-12-05 · 1 citations

  articleOpen accessCorresponding

  The formation of an appropriately shaped dendritic arbor is critical for a neuron to receive information. Dendritic morphogenesis is a dynamic process involving growth, branching, and retraction. How the growth and stabilization of dendrites are coordinated at the molecular level remains a key question in developmental neurobiology. The highly arborized and stereotyped dendritic arbors of the Caenorhabditis elegans PVD neuron are shaped by the transmembrane DMA-1 receptor through its interaction with a tripartite ligand complex consisting of SAX-7/L1CAM, MNR-1/FAM151B, and LECT-2/LECT2. However, receptor null mutants exhibit strongly reduced dendrite outgrowth, whereas ligand null mutants show disordered branch patterns, suggesting a ligand-independent function of the receptor. To test this idea, we identified point mutations in dma-1 that disrupt receptor-ligand binding and introduced corresponding mutations into the endogenous gene. We show that the ligand-free receptor is sufficient to drive robust, disordered dendritic branch formation but results in a complete loss of arbor shape. This disordered outgrowth program utilizes similar downstream effectors as the stereotyped outgrowth program, further arguing that ligand binding is not necessary for outgrowth. Finally, we demonstrate that ligand binding is required to maintain higher-order dendrites after development is complete. Taken together, our findings support a surprising model in which ligand-free and ligand-bound DMA-1 receptors have distinct functions: the ligand-free receptor promotes stochastic outgrowth and branching, whereas the ligand-bound receptor guides stereotyped dendrite morphology by stabilizing arbors at target locations.

  PublisherDOI

• Structural insights into wiring specificity in the neuromuscular system through the Beat-Side complex

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-09

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Nervous system assembly is guided by the actions of cell surface receptors. In Drosophila , members of the Beaten Path (Beat) and Sidestep (Side) protein families have been described as axon guidance receptor-cue pairs, in addition to roles in specifying synaptic connectivity in the optic lobe. To understand the molecular basis and specificity of Beat-Side interactions, we report here the first Beat-Side structure, Beat-Vc bound to Side-VI. The structure showed a binding topology similar to other neuronal immunoglobulin superfamily receptors, especially Nectins, SynCAMs, Dprs and DIPs, despite lack of established evolutionary relationships. Using a structure-based rational approach, we engineered and validated point mutations to break the binding between Beats and Sides. Using these mutant variants, we demonstrated in developing Drosophila larvae that the interaction between Beat-Ia and Side is required for establishing proper connectivity of motor neurons with muscles.

  PublisherOA PDFDOI

• Repulsive interactions instruct synaptic partner matching in an olfactory circuit

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-02 · 5 citations

  preprintOpen access

  Abstract Neurons exhibit extraordinary precision in selecting synaptic partners. Although cell-surface proteins (CSPs) mediating attractive interactions between developing axons and dendrites have been shown to instruct synaptic partner matching 1,2 , the degree to which repulsive interactions play a role is less clear. Here, using a genetic screen guided by single-cell transcriptomes 3,4 , we identified three CSP pairs—Toll2–Ptp10D, Fili–Kek1, and Hbs/Sns– Kirre—in mediating repulsive interactions between non-partner olfactory receptor neuron (ORN) axons and projection neuron (PN) dendrites in the developing Drosophila olfactory circuit. Each CSP pair exhibits inverse expression patterns in the select ORN-PN partners. Loss of each CSP in ORNs led to similar synaptic partner matching deficits as the loss of its partner CSP in PNs, and mistargeting phenotypes caused by overexpressing one CSP could be suppressed by loss of its partner CSP. All CSP pairs are also differentially expressed in other brain regions. Together, our data reveal that multiple repulsive CSP pairs work together to ensure precise synaptic partner matching during development by preventing neurons from forming connections with non-cognate partners.

  PublisherOA PDFDOI

• Structural basis and functional roles for Toll-like receptor binding to Latrophilin in C. elegans development

  EMPIAR dataset · 2025-03-24

  datasetOpen accessSenior author

  EMPIAR, the Electron Microscopy Public Image Archive centered at EMBL-EBI, is a public resource for raw electron microscopy images related to EMDB, contains micrographs, particle sets and tilt-series.

  PublisherDOI

• Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering

  Nature Communications · 2025-01-18 · 5 citations

  articleOpen access

  IFNλ4 has posed a conundrum in human immunology since its discovery in 2013, with its expression linked to complications with viral clearance. While genetic and cellular studies revealed the detrimental effects of IFNλ4 expression, extensive structural and functional characterization has been limited by the inability to express and purify the protein, complicating explanations of its paradoxical behavior. In this work, we report a method for robust production of IFNλ4. We then use yeast surface display to affinity-mature IL10Rβ and solve the 72 kilodalton structures of IFNλ4 (3.26 Å) and IFNλ3 (3.00 Å) in complex with their receptors IFNλR1 and IL10Rβ using cryogenic electron microscopy. Comparison of the structures highlights differences in receptor engagement and reveals a distinct 12-degree rotation in overall receptor geometry, providing a potential mechanistic explanation for differences in cell signaling, downstream gene induction, and antiviral activities. Further, we perform a structural analysis using molecular modeling and simulation to identify a unique region of IFNλ4 that, when replaced, enables secretion of the protein from cells. These findings provide a structural and functional understanding of the IFNλ4 protein and enable future comprehensive studies towards correcting IFNλ4 dysfunction in large populations of affected patients.

  PublisherOA PDFDOI

• Repulsive interactions instruct synaptic partner matching in an olfactory circuit

  Research Square · 2025-03-13

  preprintOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• Molecular Recognition Principles, Engineering and Function of Neural Wiring Receptors

  NIH · $1.8M · 2016–2022

• Control of neural circuit assembly by cell surface protein interactions

  NIH · $9.6M · 1990–2027

• Split RNA polymerases for sensitive, multidimensional analysis of intercellular PPIs at synapses

  NIH · $2.3M · 2017–2021

Frequent coauthors

• K. Christopher García

  Stanford University

  40 shared

• Kang Shen

  Stanford University

  15 shared

• Mili Jeon

  California Institute of Technology

  11 shared

• A. Jaworski

  Allen Institute for Brain Science

  11 shared

• E. Claver Cortés

  University of Chicago

  11 shared

• Bruno Reversade

  National University of Singapore

  10 shared

• Kai Zinn

  California Institute of Technology

  9 shared

• Pei-Tseng Lee

  Baylor College of Medicine

  9 shared

Labs

• Özkan LabPI

Education

• B.S., Molecular Biology & Genetics

  Bilkent University

  1999

• Ph.D., Molecular Biophysics

  U. of Texas Southwestern Med Ctr

  2006

• Other, Biochemistry

  Stanford University

  2013

Awards & honors

• Alfred P. Sloan Research Fellow in Neuroscience (2016)
• Klingenstein-Simons Neuroscience Fellow (2015)