Mikel Garcia-Marcos, PhD
Associate Professor
Boston University School of Medicine
Dept of Biochemistry

PhD, University of the Basque Country

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..

Targeting of Non-Canonical G Protein Signaling with Small Molecules
07/01/2018 - 06/30/2022 (PI)
NIH/National Institute of General Medical Sciences

Alternative Mechanisms of Signaling via Trimeric G Proteins
09/01/2014 - 08/31/2019 (PI)
NIH/National Institute of General Medical Sciences

Identification of chemical probes that specifically disrupt the GIV-Gi interface
01/01/2015 - 12/31/2018 (PI)
NIH/National Institute of General Medical Sciences

Student Intern Agreement with Universidad Francisco de Vitoria - Covadonga Lopez Ramos
02/01/2018 - 07/31/2018 (PI)
Universidad Francisco de Vitoria

Student Intern Agreement with Unviersidad Francisco de Vitoria-Alberto Garcia Lopez
02/01/2018 - 07/31/2018 (PI)
Universidad Francisco de Vitoria

Molecular Mechanisms and Validation of a Novel Target in Cancer
07/01/2013 - 06/30/2018 (PI)
American Cancer Society, Inc.

Student Intern Agreement with Universidad Francisco de Vitoria
02/21/2014 - 06/21/2015 (PI)
Universidad Francisco de Vitoria

Targeting a novel G protein activator for cancer therapeutics
01/01/2013 - 12/31/2013 (PI)
Elsa U. Pardee Foundation

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Martemyanov KA, Garcia-Marcos M. Making useful gadgets with miniaturized G proteins. J Biol Chem. 2018 May 11; 293(19):7474-7475. PMID: 29752421.
  2. Leyme A, Marivin A, Maziarz M, DiGiacomo V, Papakonstantinou MP, Patel PP, Blanco-Canosa JB, Walawalkar IA, Rodriguez-Davila G, Dominguez I, Garcia-Marcos M. Specific inhibition of GPCR-independent G protein signaling by a rationally engineered protein. Proc Natl Acad Sci U S A. 2017 11 28; 114(48):E10319-E10328.View Related Profiles. PMID: 29133411.
  3. DiGiacomo V, Marivin A, Garcia-Marcos M. When Heterotrimeric G Proteins Are Not Activated by G Protein-Coupled Receptors: Structural Insights and Evolutionary Conservation. Biochemistry. 2018 01 23; 57(3):255-257. PMID: 29035513.
  4. Maziarz M, Garcia-Marcos M. Rapid kinetic BRET measurements to monitor G protein activation by GPCR and non-GPCR proteins. Methods Cell Biol. 2017; 142:145-157. PMID: 28964333.
  5. Maziarz M, Garcia-Marcos M. Fluorescence polarization assays to measure interactions between Ga subunits of heterotrimeric G proteins and regulatory motifs. Methods Cell Biol. 2017; 142:133-143. PMID: 28964332.
  6. 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.
  7. 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 Gai activation by non-GPCR proteins with a Ga-Binding and Activating motif. Nat Commun. 2017 May 18; 8:15163.View Related Profiles. PMID: 28516903.
  8. 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 Dec 30; 291(53):27098-27111.View Related Profiles. PMID: 27864364; DOI: 10.1074/jbc.M116.764431;.
  9. Gupta V, Bhandari D, Leyme A, Aznar N, Midde KK, Lo IC, Ear J, Niesman I, López-Sánchez I, Blanco-Canosa JB, von Zastrow M, Garcia-Marcos M, Farquhar MG, Ghosh P. GIV/Girdin activates Gai and inhibits Gas via the same motif. Proc Natl Acad Sci U S A. 2016 09 27; 113(39):E5721-30.View Related Profiles. PMID: 27621449; DOI: 10.1073/pnas.1609502113;.
  10. Garcia-Marcos M, VanHook AM. Science Signaling Podcast for 12 April 2016: G proteins in auriculo-condylar syndrome. Sci Signal. 2016; 9(423):pc9. PMID: 27072654; DOI: 10.1126/scisignal.aaf7740;.
Showing 10 of 46 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 46 publications over 15 distinct years, with a maximum of 6 publications in 2011 and 2017

Contact for Mentoring:

72 E. Concord St Silvio Conte (K)
Boston MA 02118
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(617) 638-5339 (fax)

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