Mikel Garcia-Marcos, PhD

Professor, Biochemistry & Cell Biology

Mikel Garcia-Marcos
617.358.4396
72 E. Concord St Silvio Conte (K)

Biography

We investigate signal transduction mechanisms with the ultimate goal of elucidating the molecular basis of human diseases and developing novel therapeutic approaches.

Our main interest is in heterotrimeric G proteins, which are molecular switches that relay extracellular signals. Heterotrimeric G proteins are primarily activated by G protein-coupled receptors (GPCRs) located at the plasma membrane. However, our lab focuses on a group of cytoplasmic factors that mimic the action of GPCRs by directly activating heterotrimeric G proteins. These non-receptor activators “rewire” signal transduction in different pathological settings, including cancer, fibrosis, insulin resistance and kidney failure, among many others.

Our current efforts are focused on:
(i) identifying the members of this group of non-receptor activators
(ii) defining their role in normal and pathological scenarios
(iii) characterizing the molecular mechanisms by which they are regulated
(iv) understanding the structural basis for their action on G proteins
(v) developing tools to specifically target them.

We are currently exploring this unconventional aspect of G protein signaling in the context of cancer, embryonic development and neurotransmission.Our multidisciplinary approach includes in vitro biochemistry to characterize protein complexes, cultured cells and model organisms (yeast, frog embryos, fish) for functional studies, and synthetic biology tools to manipulate and monitor signaling with exquisite spatiotemporal resolution..

Other Positions

  • Member, BU-BMC Cancer Center, Boston University
  • Member, Evans Center for Interdisciplinary Biomedical Research, Boston University
  • Member, Genome Science Institute, Boston University

Education

  • University of the Basque Country, PhD
  • University of the Basque Country, BS

Publications

  • Published on 2/16/2024

    Janicot R, Maziarz M, Park JC, Zhao J, Luebbers A, Green E, Philibert CE, Zhang H, Layne MD, Wu JC, Garcia-Marcos M. Direct interrogation of context-dependent GPCR activity with a universal biosensor platform. Cell. 2024 Feb 16. PMID: 38412860.

    Read at: PubMed
  • Published on 2/15/2024

    Garcia-Marcos M. Heterotrimeric G protein signaling without GPCRs: The Ga-binding-and-activating motif. J Biol Chem. 2024 Feb 15; 300(3):105756. PMID: 38364891.

    Read at: PubMed
  • Published on 1/11/2024

    Cebul ER, Marivin A, Wexler LR, Perrat PN, Bénard CY, Garcia-Marcos M, Heiman MG. SAX-7/L1CAM acts with the adherens junction proteins MAGI-1, HMR-1/Cadherin, and AFD-1/Afadin to promote glial-mediated dendrite extension. bioRxiv. 2024 Jan 11. PMID: 38260503.

    Read at: PubMed
  • Published on 1/2/2024

    Janicot R, Maziarz M, Park JC, Luebbers A, Green E, Zhao J, Philibert C, Zhang H, Layne MD, Wu JC, Garcia-Marcos M. Direct interrogation of context-dependent GPCR activity with a universal biosensor platform. bioRxiv. 2024 Jan 02. PMID: 38260348.

    Read at: PubMed
  • Published on 12/19/2023

    Lao-Peregrin C, Xiang G, Kim J, Srivastava I, Fall AB, Gerhard DM, Kohtala P, Kim D, Song M, Garcia-Marcos M, Levitz J, Lee FS. Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk. Cell Rep. 2024 Jan 23; 43(1):113595. PMID: 38117654.

    Read at: PubMed
  • Published on 11/20/2023

    Luebbers A, Gonzalez-Hernandez AJ, Zhou M, Eyles SJ, Levitz J, Garcia-Marcos M. Dissecting the molecular basis for the modulation of neurotransmitter GPCR signaling by GINIP. Structure. 2024 Jan 04; 32(1):47-59.e7. PMID: 37989308.

    Read at: PubMed
  • Published on 8/28/2023

    Lao-Peregrin C, Xiang G, Kim J, Srivastava I, Fall AB, Gerhard DM, Kohtala P, Kim D, Song M, Garcia-Marcos M, Levitz J, Lee FS. Synaptic plasticity via receptor tyrosine kinase/G protein-coupled receptor crosstalk. bioRxiv. 2023 Aug 28. PMID: 37693535.

    Read at: PubMed
  • Published on 6/29/2023

    Park JC, Luebbers A, Dao M, Semeano A, Nguyen AM, Papakonstantinou MP, Broselid S, Yano H, Martemyanov KA, Garcia-Marcos M. Fine-tuning GPCR-mediated neuromodulation by biasing signaling through different G protein subunits. Mol Cell. 2023 Jul 20; 83(14):2540-2558.e12. PMID: 37390816.

    Read at: PubMed
  • Published on 6/1/2023

    Garcia-Marcos M. Stickier G-protein conformations. Nat Chem Biol. 2023 Jun; 19(6):665-666. PMID: 36646957.

    Read at: PubMed
  • Published on 6/1/2023

    Janicot R, Park JC, Garcia-Marcos M. Detecting GPCR Signals With Optical Biosensors of Ga-GTP in Cell Lines and Primary Cell Cultures. Curr Protoc. 2023 Jun; 3(6):e796. PMID: 37310083.

    Read at: PubMed

View 65 more publications: View full profile at BUMC

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