Laboratory of Translational Genomics

The Laboratory of Translational Genomics is focused on the genetics of coronary artery disease (CAD). Through unbiased Genome-Wide Association Studies (GWAS), the team has  identified common genetic variants at over 40 loci that augment the risk of CAD (Science, 2007, 316: 1488-1491; Nature Genetics, 2011, 43: 333-338; Lancet, 2011, 377: 383-392; Cell Reports, 2014, 7: 834-847). Importantly, these studies reveal novel disease mechanisms that fundamentally alter our view of CAD, beyond cholesterol and blood pressure.

Collaborative studies with the laboratory of Dr. Hsiao-Huei Chen at the Ottawa Hospital Research Institute explore cellular mechanisms underlying neurodegenerative and neurodevelopmental disorders and their links to the cardiovascular system: the Brain – Heart Axis.

Director

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Publications

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

Selected publications:

Staff

Current Team Members

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

Projects

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.

Available Positions

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