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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
- Chemical Biology and Molecular Medicine Program
Education & Training
- Washington University in St. Louis, PhD - Molecular Biophysics
- Stanford University, Postdoc - 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.
- 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 05;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 03;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.
- 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.