June 16, 2017
11 am to 12 pm EDT

Sponsored by

Webinar Description:

Once genetic and genomic variants for complex diseases are identified, it is often difficult to determine the mechanisms through which they affect disease pathogenesis. The use of metabolomics data represents an optimal approach for identifying the biological mechanisms of how these variants are operating. We demonstrate the translation utility to metabolomics through the integration of environmental exposures, genetics, and genomics through an application to asthma whereby we are able to link the causal mechanisms of asthma with the ORMDL3 locus, vitamin D exposure, and the sphingolipid pathway. Specifically we demonstrate how vitamin D interaction with the functional ORMDL3 variant using both genetics and gene expression. We also identify mediating metabolites for this affect and how these metabolites are working with both ORMDL3 and vitamin D to affect the overall sphingolipid pathway. Using this integrative approach, we demonstrate the ORMDL3 may affect important asthma metabolites and how increasing vitamin D exposure counteracts this genetic effect. This approach can be generalized to connect genetics, genomics, and the environment through the metabolome to enable translational understanding.

Learning Objectives:

• Metabolomics data provides clear insights into underlying biology and is genetic’s “perfect complement”
• Metabolomics can provide information behind the mechanisms by which genes function
• Multiple ‘omics’ data pointing to the same biological pathways builds scientific hypotheses and brings us closer to translational science

Speaker:

Jessica Lasky Su, Jessica Ann Lasky-Su, ScD

Assistant Professor in Medicine
Associate Statistician

Brigham and Women's Hospital and Harvard Medical School
Dr. Lasky-Su has spent the last 18 years focusing on the identification of genetic, genomic, and more recently metabolomic determinants for complex diseases, with a particular focus on asthma, the accumulation of which has resulted in over 100 peer-reviewed original research manuscripts.  Through GWAS, Dr. Lasky-Su identified multiple asthma variants, including variants in the HLA-DQ region as a disease variant for asthma, several pharmacogenetic variants that influence steroid response and short-acting beta agonists (GLCCI1 and ASB3), and an asthma and obesity susceptibility locus (DENND1B). These research findings have received national and international attention, which led to a keynote Dr. Lasky-Su’s methodological contributions, particularly those focused on family-based study designs, have also made a significant impact by demonstrating the utility of family-based study designs and the importance of accounting for age-dependent genetic effects. Dr. Lasky-Su’s more recent work has focused on integrative metabolomics and other omics data types. Through these efforts she has developed a metabolomics research program at the Channing Division of Network Medicine that has been highly successful and synergistic in nature, as it has drawn together a diverse group of investigators. This work has resulted in the identification of important biological determinants for asthma, in particular specific metabolites in the sphingolipid pathway that are related to ORMDL3, the most well-established asthma gene.