We are using two complementary approaches to achieve our goal of identifying and characterizing functional human genetic variants. Our first approach utilizes the iPSCORE resource, which was generated to enable both familial and association-based genetic studies of molecular and physiological phenotypes in induced pluripotent stem cells (iPSCs) and derived cell types. Our second approach involves conducting association studies in well-characterized cohorts with the goal of identifying variants that play roles in human disease and to assess their contributions to disease pathogenesis, progression, and prognosis.
iPSCORE (iPSC Collection for Omics Research)Induced pluripotent stem cells (iPSCs), derived from human adult cells and capable of being differentiated to become a variety of cell types, are a powerful tool for studying everything from molecular processes underlying human diseases to elusive genetic variants associated with human phenotypes. Over the past four years my lab has systematically derived and characterized a unique collection of iPSC lines from 222 individuals- the iPSCORE resource. We are currently using these lines to conduct genotype – molecular phenotype correlations in both pluripotent stem cells and iPSC-derived cell types. We have recently completed generating iPSC-derived cardiomyoctyes from over 140 individuals and are in the process of analyzing how inherited coding and regulatory variants influence molecular phenotypes (gene expression, epigenomic profiles, and protein expression) and adverse drug reactions.
Human genetic studies
We collaborate with Dr. John-Bjarne Hansen at the University of Tromso to study the genetic underpinnings ofVenous Thrombosis Embolism (VTE). This multi-PI study is funded through theK.G. Jebsen Medical Foundation to analyze the Tromso cohort, which is comprised of individuals who have been clinically followed for several decades. Our lab has sequenced thousands of individuals in the Tromso cohort and we are now analyzing these data to identify genetic associations with VTE.
We also collaborate with Dr. Radha Ayyagari at the Shiley Eye Institute at UC San Diego to identify new genes involved in inherited retinal dystrophies (IRD). We have generated whole genome sequence (WGS) data for 454 individuals from 126 pedigrees segregating IRD; 227 subjects are affected by IRD and 227 are unaffected. Our analyses have identified new genes that can underlie IRD as well as new types of mutations that can be present in known IRD genes. The study is funded by the NEI and the Foundation Fighting Blindness.