Mikel Garcia-Marcos, PhD
Professor, Biochemistry & Cell Biology
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
Websites
Education
- University of the Basque Country, PhD
- University of the Basque Country, BS
Publications
- Published on 1/21/2025
Liebing AD, Rabe P, Krumbholz P, Zieschang C, Bischof F, Schulz A, Billig S, Birkemeyer C, Pillaiyar T, Garcia-Marcos M, Kraft R, Stäubert C. Succinate receptor 1 signaling mutually depends on subcellular localization and cellular metabolism. FEBS J. 2025 Jan 21. PMID: 39838520.
Read at: PubMed - Published on 12/18/2024
Ferreras-Gutiérrez M, Mínguez-Toral M, Ibáñez de Opakua A, Martín-Santamaría S, García-Marcos M, Medrano FJ, Blanco FJ. Integrated NMR-crystallography-computational approach for molecular recognition studies of human Gai3 protein by a small molecule inhibitor. Int J Biol Macromol. 2025 Feb; 290:138977. PMID: 39706421.
Read at: PubMed - Published on 10/11/2024
Janicot R, Garcia-Marcos M. Protocol to investigate G protein-coupled receptor signaling kinetics and concentration-dependent responses using ONE-GO biosensors. STAR Protoc. 2024 Dec 20; 5(4):103383. PMID: 39395175.
Read at: PubMed - Published on 10/1/2024
Janicot R, Garcia-Marcos M. Protocol for detecting endogenous GPCR activity in primary cell cultures using ONE-GO biosensors. STAR Protoc. 2024 Dec 20; 5(4):103355. PMID: 39356642.
Read at: PubMed - Published on 8/22/2024
Luebbers A, Janicot R, Zhao J, Philibert CE, Garcia-Marcos M. Direct detection of endogenous Gai activity in cells with a sensitive conformational biosensor. bioRxiv. 2024 Aug 22. PMID: 39229046.
Read at: PubMed - Published on 8/16/2024
Janicot R, Garcia-Marcos M. Get Ready to Sharpen Your Tools: A Short Guide to Heterotrimeric G Protein Activity Biosensors. Mol Pharmacol. 2024 Aug 16; 106(3):129-144. PMID: 38991745.
Read at: PubMed - Published on 7/24/2024
Philibert CE, Garcia-Marcos M. Smooth operator(s): dialing up and down neurotransmitter responses by G-protein regulators. Trends Cell Biol. 2025 Apr; 35(4):330-340. PMID: 39054106.
Read at: PubMed - Published on 2/26/2024
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 Mar 14; 187(6):1527-1546.e25. PMID: 38412860.
Read at: PubMed - Published on 2/15/2024
Garcia-Marcos M. Heterotrimeric G protein signaling without GPCRs: The Ga-binding-and-activating (GBA) motif. J Biol Chem. 2024 Mar; 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
View 72 more publications: View full profile at BUMC