Laboratoire de recherche translationnelle en génomique

Le Laboratoire de recherche translationnelle en génomique cardiovasculaire se consacre à la génétique de la coronaropathie.

Son équipe mène des études, non biaisées, d’associations pangénomiques qui lui ont déjà permis d’identifier 40 variantes génétiques courantes sur plus de 40 loci augmentant le risque de coronaropathie ( Science, 2007, vol. 316, p. 1488-1491; Nature Genetics, 2011, vol. 43, p. 333-338; Lancet, 2011, vol. 377, p. 383-392; Cell Reports, 2014, vol. 7, p. 834-847).

Une de ses réalisations majeures est la découverte de divers mécanismes à la base de la coronaropathie, lesquels obligent à considérer cette maladie sous un angle bien plus vaste que celui de son association à l’hypercholestérolémie et à l’hypertension artérielle.

Des études menées en collaboration avec le laboratoire de la chercheuse Hsiao-Huei Chen à l’Institut de recherche de l’Hôpital d’Ottawa explorent les mécanismes cellulaires qui sous-tendent les troubles neurodégénératifs et neurodéveloppementaux ainsi que leurs liens avec le système cardiovasculaire : l’axe cerveau/cœur.

Pour en savoir plus, veuillez consulter la page anglaise.

Directeur

Sur cette page

Publications

See current publications list at PubMed.
See Research Gate profile
See Google Scholar profile.

Selected publications:

Personnel

Current Team Members

  • Ragnar Vilmundarson, PhD Candidate
  • Fariborz Soheili, PhD Candidate
  • An Duong, MSc student on PhD track
  • Niloufar Heydarikhorneh, research technician

Projets

The Laboratory of Translational Genomics is currently working on three loci, 9p21, SPG7 and IRF2BP2, to elucidate their biological impact on CAD risk and to transform GWAS discoveries to therapeutic applications. 

Genetic Loci for Cardiovascular Disease

The 9p21 locus (with 52 linked variants) is the first genetic risk factor for CAD identified by 3 independent GWAS, including ours (Science, 2007, 316: 1488-1491). We found that it disrupts regulatory sequences and affects expression of genes controlling cell proliferation (ATVB, 2009, 29(10): 1671-1677; JACC, 2013, 61(2): 143-147). The laboratory is addressing mechanisms affected by 9p21 variants, including disrupted regulation by TEAD transcription factors and how this disruption impacts vascular cell proliferation and atherosclerosis progression.

Dr. Stewart is a founding member of the international CARDIoGRAM consortium comprising GWAS of > 20 centres in 8 countries for the discovery of genetic risk of CAD. CARDIoGRAM has published the landmark papers on the genetics of CAD.

Inflammation

The laboratory’s recent work shows that a novel regulator of innate immunity, IRF2BP2, suppresses macrophage inflammation, promotes macrophage cholesterol handling and limits foam cell formation. The team discovered a deletion variant that disrupts an RNA-binding protein target in the human IRF2BP2 3’UTR, lowers protein levels and increases CAD risk. Dr. Stewart and his collaborators have made transgenic mice that delete IRF2BP2 in macrophages and found increased propensity to develop atherosclerosis.  They are using this unique mouse model to reveal key cellular pathways and potential therapeutic targets regulated by IRF2BP2 that affect cardiac repolarization in sepsis.

Offres d'emploi

Opportunities

To enquire about available positions, please submit your CV with a cover letter detailing what you can bring to the team.

Collaborations

The laboratory has ongoing collaborations with faculty at the Ottawa Hospital Research Institute (H-H Chen).

Contact
@email
613-696-7353