Understanding how genetic information is decoded to produce the complex regulatory systems driving disease remains a great challenge in biomedical sciences. However, the increasing availability of high-dimensional molecular, cellular and phenotypic data now allows a comprehensive investigation of the complex genetic and regulatory mechanisms that underlie the disease process.
Our research lab focuses on the systems-level integration of genetic, functional genomic and phenotypic data to identify causal determinants and pathways of complex traits and disease, with a focus on cardio-metabolic, inflammatory and neuropsychiatric disorders. To this aim, we have developed an integrated genetic and gene-network approach, called Systems-Genetics, to determine the consequences of key genetic variants ('master genetic regulators') on functional gene-networks in disease.
To date, using Systems-Genetics we have uncovered several genes regulating functional gene-networks underling disease processes, including EBI2 regulating an anti-viral expression network and type 1 diabetes risk, KCNN4 and its co-regulatory network underlying cell multinucleation in inflammatory disease and SESN3 as a master genetic regulator of a proconvulsant gene network in human epileptic hippocampus. Our Systems-Genetics strategy will be further developed to study cardio-metabolic traits and disease, with the aim of deciphering the primary genetic factors and regulatory networks underlying hypertrophy, remodeling and fibrosis in the human heart.
Centre for Computational Biology, 8 College Road, Singapore, 169857