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

PhD, University of 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..

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

Identification of chemical probes that specifically disrupt the GIV-Gi interface
01/01/2015 - 12/31/2017 (PI)
NIH/National Institute of General Medica

Alternative Mechanisms of Signaling via Trimeric G Proteins
09/01/2014 - 08/31/2017 (PI)
NIH/National Institute of General Medica

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. 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 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.
  3. 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 Sep 27; 113(39):E5721-30.View Related Profiles. PMID: 27621449; DOI: 10.1073/pnas.1609502113;.
  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 Apr 12; 9(423):ra37.View Related Profiles. PMID: 27072656; PMCID: PMC4870087; DOI: 10.1126/scisignal.aad2429;.
  5. Leyme A, Marivin A, Garcia-Marcos M. GIV/Girdin (Ga-interacting, Vesicle-associated Protein/Girdin) Creates a Positive Feedback Loop That Potentiates Outside-in Integrin Signaling in Cancer Cells. J Biol Chem. 2016 Apr 8; 291(15):8269-82.View Related Profiles. PMID: 26887938; PMCID: PMC4825026; DOI: 10.1074/jbc.M115.691550;.
  6. 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; PMCID: PMC4760084; DOI: 10.1093/molbev/msv336;.
  7. 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.View Related Profiles. PMID: 26391662; PMCID: PMC4586755; DOI: 10.1083/jcb.201506041;.
  8. Bhandari D, Lopez-Sanchez I, To A, Lo IC, Aznar N, Leyme A, Gupta V, Niesman I, Maddox AL, Garcia-Marcos M, Farquhar MG, Ghosh P. Cyclin-dependent kinase 5 activates guanine nucleotide exchange factor GIV/Girdin to orchestrate migration-proliferation dichotomy. Proc Natl Acad Sci U S A. 2015 Sep 1; 112(35):E4874-83.View Related Profiles. PMID: 26286990; PMCID: PMC4568279; DOI: 10.1073/pnas.1514157112;.
  9. 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; PMCID: PMC4484057; DOI: 10.7554/eLife.07091;.
  10. 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; PMCID: PMC4358093; DOI: 10.1074/jbc.R114.613414;.
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This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 39 publications over 14 distinct years, with a maximum of 6 publications in 2011

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

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