Vince Luca, PhD

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.

Associations

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

Education & Training

Graduate:

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

Fellowship:

• Stanford University - Molecular and Cellular Physiology

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.

• Perez DH, Antfolk D, Chang S, Bustos XE, Medina E, Ramadan AA, Gonzalez-Perez D, Abate-Daga D, Rodriguez PC, Luca VC. Engineering synthetic agonists for targeted activation of Notch signaling. Nat Chem Biol. 2025 Sep. Pubmedid: 40993428.
• Ming Q, Luca VC. A little "BiTS" of LAG3 agonism, a big effect on T-cell autoimmunity. Immunol Cell Biol. 2025 Nov. Pubmedid: 41177146.
• Luca VC. LAG Time in the Era of Immunotherapy-New Molecular Insights Into the Immunosuppression Mechanism of Lymphocyte Activation Gene-3. Immunol Rev. 2025 Mar.330(1):e70002. Pubmedid: 39887765. Pmcid: PMC11917464.
• Antfolk D, Ming Q, Manturova A, Goebel EJ, Thompson TB, Luca VC. Molecular mechanism of Activin receptor inhibition by DLK1. Nat Commun. 2025 Jul.16(1):5976. Pubmedid: 40593645. Pmcid: PMC12216052.
• Phadke MS, Li J, Sriramareddy S, Rodriguez PC, Ruffell B, Luca VC, Tran TTT, Chen YA, Smalley KSM. Identification of anti-TIM-3 based checkpoint inhibitor combinations with activity in immunotherapy refractory melanoma models. J Immunother Cancer. 2025 Aug.13(8). Pubmedid: 40825611. Pmcid: PMC12366563.
• Singh S, Julia E, Kalita P, Mason C, Ming Q, Lee-Sam A, Gordon S, Buitrago ME, Leung DW, Hwu P, Luca VC. Structure-guided engineering of CD112 receptor variants for optimized immunotherapy. Mol Ther. 2025 Aug.33(8):3590-3604. Pubmedid: 40285356. Pmcid: PMC12368799.
• Foran G, Hallam RD, Megaly M, Turgambayeva A, Antfolk D, Li Y, Luca VC, Necakov A. Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping. Sci Rep. 2024 Sep.14(1):21912. Pubmedid: 39300145. Pmcid: PMC11413390.
• Fowler JL, Zheng SL, Nguyen A, Chen A, Xiong X, Chai T, Chen JY, Karigane D, Banuelos AM, Niizuma K, Kayamori K, Nishimura T, Cromer MK, Gonzalez-Perez D, Mason C, Liu DD, Yilmaz L, Miquerol L, Porteus MH, Luca VC, Majeti R, Nakauchi H, Red-Horse K, Weissman IL, Ang LT, Loh KM. Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells. Dev Cell. 2024 May.59(9):1110-1131.e22. Pubmedid: 38569552. Pmcid: PMC11072092.
• 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.
• Perez DH, Antfolk D, Medina E, Gonzalez-Perez D, Luca VC. Engineering synthetic agonists for targeted activation of Notch signaling. bioRxiv. 2024 Aug. Pubmedid: 39149362. Pmcid: PMC11326249.
• Gilbert MA, Keefer-Jacques E, Jadhav T, Antfolk D, Ming Q, Valente N, Shaw GT, Sottolano CJ, Matwijec G, Luca VC, Loomes KM, Rajagopalan R, Hayeck TJ, Spinner NB. Functional characterization of 2,832 JAG1 variants supports reclassification for Alagille syndrome and improves guidance for clinical variant interpretation. Am J Hum Genet. 2024 Aug.111(8):1656-1672. Pubmedid: 39043182. Pmcid: PMC11339624.
• Foran G, Hallam RD, Megaly M, Turgambayeva A, Antfolk D, Li Y, Luca VC, Necakov A. Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping. bioRxiv. 2024 Aug. Pubmedid: 39131356. Pmcid: PMC11312450.
• Ming Q, Antfolk D, Price DA, Manturova A, Medina E, Singh S, Mason C, Tran TH, Smalley KSM, Leung DW, Luca VC. Structural basis for mouse LAG3 interactions with the MHC class II molecule I-Ab. Nat Commun. 2024 Aug.15(1):7513. Pubmedid: 39209860. Pmcid: PMC11362559.
• 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.

• Title: Structure-function studies of LAG3 interactions with antibodies and cellular ligands
  Award Number: 1R01CA299899-01
  Sponsor: National Cancer Institute (NCI)
  Luca, V. (PD/PI), Smalley, K. (Co-PD/PI)
• Title: Illuminating Notch receptor-ligand selectivity through structure-guided protein engineering
  Award Number: 2R35GM133482-06
  Sponsor: National Institute of General Medical Sciences (NIGMS)
  Luca, V. (PD/PI)
• Title: Structure and Biophysics of CD24 Interactions
  Award Number: 22VA012
  Sponsor: PHEAST THERAPEUTICS INC.
  Luca, V. (PD/PI)
• Title: Structure and biophysics of CD24 interactions
  Award Number: 22VA012.001, First Amendment
  Sponsor: PHEAST THERAPEUTICS INC.
  Luca, V. (PD/PI)
• Title: Engineering Bispecific Nanobodies for Detection of Breast Cancer Nodal Metastasis
  Award Number: W81XWH-22-1-0081, Log #BC210261P3
  Sponsor: Department of Defense (DOD)
  Luca, V. (PD/PI)
• Title: Targeting ENPP1 to promote immunity during PARP inhibition in TNBC
  Award Number: W81XWH2210407 Log# BC211038P1
  Sponsor: Department of Defense (DOD)
  Luca, V. (PD/PI)
• Title: Impact and Utilization of Scalable Functional Assays in Alagille Syndrome
  Award Number: R01DK140468-01
  Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  Luca, V. (PD/PI)
• Title: Structure-guided engineering of LAG3 immunomodulatory function
  Award Number: 22B07
  Sponsor: Florida Department of Health
  Luca, V. (PD/PI)