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Vince  Luca

Vince Luca, PhD

Program: Immunology

Research Program: Molecular Medicine Program


  • Overview

    The Luca Lab studies the "molecular language" of cell-to-cell communication using cutting edge approaches in structural, cellular and synthetic biology. Our goal is to visualize how cells send and receive information at the atomic level, and to harness this insight to guide the engineering of next-generation cancer therapeutics.


    • Drug Discovery
    • Malignant Hematology
    • Immunology
    • Molecular Medicine Program
    • Melanoma & Skin Cancer Center of Excellence

    Education & Training


    • Washington University in St. Louis, PhD - Molecular Biophysics


    • Stanford University - Molecular and Cellular Physiology
  • Research Interest

    Dr. Luca's research harnesses the power of directed evolution to understand how molecular signals control cellular behavior. Directed evolution enables us to evolve proteins "in a test tube" by generating millions of mutants and then selecting the "winners" with the best functional properties. We study these unique variants to determine how cellular receptors become activated and to guide the development of precisely targeted therapeutics. Our expertise with yeast display allows us to evolve complex eukaryotic proteins, which creates new avenues for the manipulation of difficult-to-target mammalian signaling pathways. Current projects in the lab integrate directed evolution with x-ray crystallography, computational modeling, and cell biology to illuminate receptor systems involved in the development of stem cells.

  • Publications

    • Smyrlaki I, Fördős F, Rocamonde-Lago I, Wang Y, Shen B, Lentini A, Luca VC, Reinius B, Teixeira AI, Högberg B. Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force. Nat Commun. 2024 Jan.15(1):465. Pubmedid: 38238313. Pmcid: PMC10796381.
    • Gonzalez-Perez D, Das S, Antfolk D, Ahsan HS, Medina E, Dundes CE, Jokhai RT, Egan ED, Blacklow SC, Loh KM, Rodriguez PC, Luca VC. Affinity-matured DLL4 ligands as broad-spectrum modulators of Notch signaling. Nat Chem Biol. 2023 Jan.19(1):9-17. Pubmedid: 36050494. Pmcid: PMC10132381.
    • Lester DK, Burton C, Gardner A, Innamarato P, Kodumudi K, Liu Q, Adhikari E, Ming Q, Williamson DB, Frederick DT, Sharova T, White MG, Markowitz J, Cao B, Nguyen J, Johnson J, Beatty M, Mockabee-Macias A, Mercurio M, Watson G, Chen PL, McCarthy S, MoranSegura C, Messina J, Thomas KL, Darville L, Izumi V, Koomen JM, Pilon-Thomas SA, Ruffell B, Luca VC, Haltiwanger RS, Wang X, Wargo JA, Boland GM, Lau EK. Fucosylation of HLA-DRB1 regulates CD4+ T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy. Nat Cancer. 2023 Feb.4(2):222-239. Pubmedid: 36690875. Pmcid: PMC9970875.
    • Medina E, Easa Y, Lester DK, Lau EK, Sprinzak D, Luca VC. Structure of the planar cell polarity cadherins Fat4 and Dachsous1. Nat Commun. 2023 Feb.14(1):891. Pubmedid: 36797229. Pmcid: PMC9935876.
    • Medina E, Perez DH, Antfolk D, Luca VC. New tricks for an old pathway: emerging Notch-based biotechnologies and therapeutics. Trends Pharmacol Sci. 2023 Dec.44(12):934-948. Pubmedid: 37891017.
    • Khamaisi B, Luca VC, Blacklow SC, Sprinzak D. Functional Comparison between Endogenous and Synthetic Notch Systems. ACS Synth Biol. 2022 Oct.11(10):3343-3353. Pubmedid: 36107643. Pmcid: PMC9594772.
    • Ming Q, Celias DP, Wu C, Cole AR, Singh S, Mason C, Dong S, Tran TH, Amarasinghe GK, Ruffell B, Luca VC. LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition. Nat Immunol. 2022 Jul.23(7):1031-1041. Pubmedid: 35761082. Pmcid: PMC10191176.
    • Watson G, Lester D, Ren H, Forsyth CM, Medina E, Gonzalez Perez D, Darville L, Yao J, Luca V, Koomen J, Cen L, Lau E. Fucosylated Proteome Profiling Identifies a Fucosylated, Non-Ribosomal, Stress-Responsive Species of Ribosomal Protein S3. Cells. 2021 May.10(6). Pubmedid: 34070332. Pmcid: PMC8228307.
    • de Mingo Pulido Á, Hänggi K, Celias DP, Gardner A, Li J, Batista-Bittencourt B, Mohamed E, Trillo-Tinoco J, Osunmakinde O, Peña R, Onimus A, Kaisho T, Kaufmann J, McEachern K, Soliman H, Luca VC, Rodriguez PC, Yu X, Ruffell B. The inhibitory receptor TIM-3 limits activation of the cGAS-STING pathway in intra-tumoral dendritic cells by suppressing extracellular DNA uptake. Immunity. 2021 Jun.54(6):1154-1167.e7. Pubmedid: 33979578. Pmcid: PMC8192496.
    • Wang Z, Zhang M, Quereda V, Frydman SM, Ming Q, Luca VC, Duckett DR, Ji H. Discovery of an Orally Bioavailable Small-Molecule Inhibitor for the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction. J Med Chem. 2021 Aug.64(16):12109-12131. Pubmedid: 34382808. Pmcid: PMC8817233.
    • Luca VC, Miao Y, Li X, Hollander MJ, Kuo CJ, Garcia KC. Surrogate R-spondins for tissue-specific potentiation of Wnt Signaling. PLoS One. 2020 Jan.15(1):e0226928. Pubmedid: 31914456. Pmcid: PMC6949110.
    • Payne KK, Mine JA, Biswas S, Chaurio RA, Perales-Puchalt A, Anadon CM, Costich TL, Harro CM, Walrath J, Ming Q, Tcyganov E, Buras AL, Rigolizzo KE, Mandal G, Lajoie J, Ophir M, Tchou J, Marchion D, Luca VC, Bobrowicz P, McLaughlin B, Eskiocak U, Schmidt M, Cubillos-Ruiz JR, Rodriguez PC, Gabrilovich DI, Conejo-Garcia JR. BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells. Science. 2020 Aug.369(6506):942-949. Pubmedid: 32820120. Pmcid: PMC7646930.
    • Ming Q, Gonzalez-Perez D, Luca VC. Molecular engineering strategies for visualizing low-affinity protein complexes. Exp Biol Med (Maywood). 2019 Dec.244(17):1559-1567. Pubmedid: 31184923. Pmcid: PMC6920673.
    • Lim JS, Ibaseta A, Fischer MM, Cancilla B, O'Young G, Cristea S, Luca VC, Yang D, Jahchan NS, Hamard C, Antoine M, Wislez M, Kong C, Cain J, Liu YW, Kapoun AM, Garcia KC, Hoey T, Murriel CL, Sage J. Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature. 2017 May.545(7654):360-364. Pubmedid: 28489825. Pmcid: PMC5776014.
    • Yan KS, Janda CY, Chang J, Zheng GXY, Larkin KA, Luca VC, Chia LA, Mah AT, Han A, Terry JM, Ootani A, Roelf K, Lee M, Yuan J, Li X, Bolen CR, Wilhelmy J, Davies PS, Ueno H, von Furstenberg RJ, Belgrader P, Ziraldo SB, Ordonez H, Henning SJ, Wong MH, Snyder MP, Weissman IL, Hsueh AJ, Mikkelsen TS, Garcia KC, Kuo CJ. Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal. Nature. 2017 May.545(7653):238-242. Pubmedid: 28467820. Pmcid: PMC5641471.
    • Luca VC, Kim BC, Ge C, Kakuda S, Wu D, Roein-Peikar M, Haltiwanger RS, Zhu C, Ha T, Garcia KC. Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity. Science. 2017 Mar.355(6331):1320-1324. Pubmedid: 28254785. Pmcid: PMC5459593.
    • Zuiani A, Chen K, Schwarz MC, White JP, Luca VC, Fremont DH, Wang D, Evans MJ, Diamond MS. A Library of Infectious Hepatitis C Viruses with Engineered Mutations in the E2 Gene Reveals Growth-Adaptive Mutations That Modulate Interactions with Scavenger Receptor Class B Type I. J Virol. 2016 Dec.90(23):10499-10512. Pubmedid: 27630236. Pmcid: PMC5110168.
    • Spangler JB, Tomala J, Luca VC, Jude KM, Dong S, Ring AM, Votavova P, Pepper M, Kovar M, Garcia KC. Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms. Immunity. 2015 May.42(5):815-825. Pubmedid: 25992858. Pmcid: PMC4439582.
    • Luca VC, Jude KM, Pierce NW, Nachury MV, Fischer S, Garcia KC. Structural biology. Structural basis for Notch1 engagement of Delta-like 4. Science. 2015 Feb.347(6224):847-853. Pubmedid: 25700513. Pmcid: PMC4445638.
    • Luca VC, Nelson CA, Fremont DH. Structure of the St. Louis encephalitis virus postfusion envelope trimer. J Virol. 2013 Jan.87(2):818-828. Pubmedid: 23115296. Pmcid: PMC3554068.
    • Luca VC, AbiMansour J, Nelson CA, Fremont DH. Crystal structure of the Japanese encephalitis virus envelope protein. J Virol. 2012 Feb.86(4):2337-2346. Pubmedid: 22156523. Pmcid: PMC3302414.
    • Sabo MC, Luca VC, Prentoe J, Hopcraft SE, Blight KJ, Yi M, Lemon SM, Ball JK, Bukh J, Evans MJ, Fremont DH, Diamond MS. Neutralizing monoclonal antibodies against hepatitis C virus E2 protein bind discontinuous epitopes and inhibit infection at a postattachment step. J Virol. 2011 Jul.85(14):7005-7019. Pubmedid: 21543495. Pmcid: PMC3126585.
  • Grants

    • Title: Structure and Biophysics of CD24 Interactions
      Sponsor: Pheast Therapeutics
      PI: Luca, V.
    • Title: Targeting ENPP1 to promote immunity during PARP inhibition in TNBC
      Sponsor: US Army
      PI: Luca, V.
    • Title: Structure-guided engineering of LAG3 immunomodulatory function
      Sponsor: Florida Biomedical Research Program (FBRP)
      PI: Luca, V.
    • Title: Engineering Bispecific Nanobodies for Detection of Breast Cancer Nodal Metastasis
      Sponsor: US Army
      PI: Luca, V.
    • Title: Illuminating Notch receptor-ligand selectivity through structure-guided protein engineering
      Sponsor: Nat Institutes of Health
      PI: Luca, V.
    • Title: Illuminating Notch receptor-ligand selectivity through structure-guided protein engineering
      Sponsor: Nat Institutes of Health
      PI: Luca, V.
    • Title: Reprogramming Transmembrane ubiquitin Ligases To Control Cell Surface Receptor Landscapes.
      Sponsor: Rita Allen Foundation
      PI: Luca, V.

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