Genetic diseases of the extracellular matrix in cardiovascular pathophysiology: the Marfan syndrome

REF: PD 34
Principle investigator:
Gustavo Egea
Contact details:



Research framework

The aim of our research is to find out the impaired molecular mechanisms that explain the pathological alterations that occur at the cardiovascular system in the Marfan syndrome (MFS). MFS is a severe systemic disorder that can lead to aortic aneurysms, ocular lens dislocation, emphysema and bone overgrowth (de Paepe et al., 1996, Am. J. Med. Genet.62:417-26). This pathology results from mutations in the fibrilin-1 gene (FBN1) that encodes fibrillin-1, a constitutive component of elastic fibers (Dietz et al, 1991, Nature 352:337-9). It is widely accepted that this disease is a compendium of alterations that synergically result from alterations in the extracellular matrix (ECM) assembly and formation and the promiscuous activation of the TGFβ -mediated signalling (Neptune et al. 2003 Nat. Genet. 33:407-11). In our lab we focus our research in three major problems: (1) the endocytic trafficking of TGFβ receptors, which largely determinates the final TGFβ signalling response (di Guglielmo et al, 2003 Nat. Cell Biol. 5:680-92); (2) the expression and functional regulation mediated by integrins in the necessary crosstalk between the altered ECM and the permanently altered TGFβ signalling; and (3) the oxidative stress response by cardiovascular cells and its functional significance to the chronic TGFβ signalling. The working model of MFS we use is the aortic tissue and culture vascular smooth muscle cells obtained from aortic tunica media from a heterozygous murine model of MFS (Habashi et al., Science 312:117-21) and from human patients submitted to ascending aorta surgery. Our group has large experience in membrane trafficking and its functional integration with the actin cytoskeleton dynamics and signalling.

Some relevant publications of the group are the following:

  • Valderrama et al (2000). PNAS 97:1560-65
  • Babia et al. (2001) Traffic 2: 395-405
  • Luna et al. (2002) Mol. Biol. Cell 13: 866-879
  • Duran et al. (2003) Mol. Biol. Cell 14: 445-59
  • Matas et al (2004) Traffic 5:838-46
  • Egea et al. (2006) Cur. Opin. Cell Biol. 18: 168-78
  • Fernández-Ulibarri et al. (2007) Mol. Cell Biol. 18: 3250-63
  • Lázaro-Diéguez et al. (2008) J. Cell Sci. 121:1415-25
  • Selva et al (2010) J. Am. Chem. Soc. 132:6947-54
  • Sarri et al. (2011) J. Biol. Chem. 286:28632-43

Regular techniques used in the lab are light and electron microscope techniques, DNA transfection techniques, silencing mRNA, subcellular fractionation, cell adhesion and migration assays, western blot techniques, cell microinjection among others


Marfan syndrome, TGFβ, aortic aneurysm, membrane trafficking, integrins, oxidative stress

Main Challenges

Our main challenge is to provide to the scientific and medical community new knowledge about the basic mechanisms involved in the generation of MFS and reveal in this way new potential specific molecular targets that can be pharmacological or molecularly afforded. It is also possible that our findings might be extrapolated to other genetically-originated diseases where other ECM proteins and growth factors play a pivotal role in the generation and/or progression of the disease.

The candidate should have the basic cell and molecular biology skills to work in an enthusiastic scientific environment where basic and clinical researchers work in a translational manner. The candidate will conduct his/her research being highly integrative with the other team members and clinicians of the Marfan Unit of Barcelona as well as other connected international labs also working in MFS and related diseases such Loeys-Dietz symdrome, Williams syndrome.

Team strategic objective in IDIBAPS

The basic research experience offer by our group will provide not only knowledge of the molecular mechanisms involved in the cardiovascular pathological manifestations in the MFS, but also to reveal new potential targets for therapeutical treatments, where aortic dissection is the case of 1-2% of death in western countries. This disease is also an excellent model to address and understand how the ECM influences and/or determines in a large extent the signalling and adaptive response of cells in cardiovascular tissues, paying particular attention to the ascending and thoracic aorta.

(Read eligibility criteria)