• Title Assistant Professor
  • Education PhD: University of the Basque Country/ Universite Libre de Bruxelles
    Postdoctoral Training: University of California, San Diego
  • Office 617-638-4047
  • Phone 617-638-4047
  • Area of Interest G protein signaling circuits in the molecular basis of disease

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 and (v) developing tools to specifically target them. We are 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, culture cells and model organisms (yeast, frog embryos) for functional studies and synthetic biology tools to manipulate and monitor signaling with exquisite spatiotemporal resolution.

Vincent di Giacomo – Postdoctoral Associate
Arthur Marivin – Postdoctoral Associate
Marcin MaziarzPostdoctoral Associate
Maria PapakonstantinouPostdoctoral Associate
Isha WalawalkarUndergraduate Student
Jillian Norris – Undergraduate Student
Prachi Patel – Undergraduate Student

Postdoctoral positions available. Check here.

  1. DiGiacomo V, de Opakua AI, Papakonstantinou MP, Nguyen LT, Merino N, Blanco-Canosa JB, Blanco FJ, Garcia-Marcos M. The Gai-GIV binding interface is a druggable protein-protein interaction. Sci Rep. 2017 Aug 17; 7(1):8575. PMID: 28819150.
  2. de Opakua AI, Parag-Sharma K, DiGiacomo V, Merino N, Leyme A, Marivin A, Villate M, Nguyen LT, de la Cruz-Morcillo MA, Blanco-Canosa JB, Ramachandran S, Baillie GS, Cerione RA, Blanco FJ, Garcia-Marcos M. Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif. Nat Commun. 2017 May 18;8:15163. doi: 10.1038/ncomms15163. PMID: 28516903. View in: PubMed
  3. Parag-Sharma K, Leyme A, DiGiacomo V, Marivin A, Broselid S, Garcia-Marcos M. Membrane Recruitment of the Non-receptor Protein GIV/Girdin (Ga-interacting, Vesicle-associated Protein/Girdin) Is Sufficient for Activating Heterotrimeric G Protein Signaling. J Biol Chem. 2016 Nov 18. PMID: 27864364. View in: PubMed
  4. Marivin A, Leyme A, Parag-Sharma K, DiGiacomo V, Cheung AY, Nguyen LT, Dominguez I, Garcia-Marcos M. Dominant-negative Ga subunits are a mechanism of dysregulated heterotrimeric G protein signaling in human disease. Sci Signal. 2016; 9(423):ra37. PMID: 27072656. View in: PubMed
  5. Coleman BD, Marivin A, Parag-Sharma K, DiGiacomo V, Kim S, Pepper JS, Casler J, Nguyen LT, Koelle MR, Garcia-Marcos M. Evolutionary Conservation of a GPCR-Independent Mechanism of Trimeric G Protein Activation. Mol Biol Evol. 2016 Mar; 33(3):820-37. PMID: 26659249. View in: PubMed
  6. Leyme A, Marivin A, Perez-Gutierrez L, Nguyen LT, Garcia-Marcos M. Integrins activate trimeric G proteins via the nonreceptor protein GIV/Girdin. J Cell Biol. 2015 Sep 28; 210(7):1165-84. PMID: 26391662. View in: PubMed
  7. Aznar N, Midde KK, Dunkel Y, Lopez-Sanchez I, Pavlova Y, Marivin A, Barbazán J, Murray F, Nitsche U, Janssen KP, Willert K, Goel A, Abal M, Garcia-Marcos M, Ghosh P. Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling. Elife. 2015; 4:e07091. PMID: 26126266. View in: PubMed
  8. Garcia-Marcos M, Ghosh P, Farquhar MG. GIV/Girdin transmits signals from multiple receptors by triggering trimeric G protein activation. J Biol Chem. 2015 Mar 13; 290(11):6697-704. PMID: 25605737. View in: PubMed
  9. Garcia-Marcos M, Kietrsunthorn PS, Pavlova Y, Adia MA, Ghosh P, Farquhar MG. Functional characterization of the guanine nucleotide exchange factor (GEF) motif of GIV protein reveals a threshold effect in signaling. Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):1961-6. doi: 10.1073/pnas.1120538109. Epub 2012 Jan 25. PMID: 22308453. View in: PubMed
  10. Garcia-Marcos M, Ghosh P, Farquhar MG. Molecular basis of a novel oncogenic mutation in GNAO1. Oncogene. 2011 Jun 9;30(23):2691-6. doi: 10.1038/onc.2010.645. Epub 2011 Feb 14. PMID: 21317923. View in: PubMed
  11. Garcia-Marcos M, Ghosh P, Farquhar MG. GIV is a nonreceptor GEF for G alpha i with a unique motif that regulates Akt signaling. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3178-83. doi: 10.1073/pnas.0900294106. Epub 2009 Feb 11. PMID: 19211784. View in: PubMed

Complete list can be found at BU Profiles

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