Current Research and Scholarly Interests
Current Research:
While technological advances have enabled the association of thousands of genetic variants to complex traits of health and disease, we lack a comprehensive understanding of how genetic variation governs phenotypic diversity and disease. This is largely due to the challenge of discovering the mechanisms through which genetic variation shape cellular phenotypes, as well as the complex interplay between variants and the impact of environmental factors. Our research is directed at developing genomics technologies and approaches to study the molecular processes that underlie complex genetic traits, gene regulation, and inherited diseases. Our approach has been to drive technology development together with biological application, in which we work across the broad axis of fundamental to translational research.
Our research is multi-faceted, including experimental and computational approaches:
Precision Health: We work with model organisms, ranging from induced pluripotent stem cells to mice and humans, to study genetic and cellular mechanisms in diseases and to assess potential treatments. We apply genome analysis and CRISPR editing to study human diseases, like dilated cardiomyopathy, immune disorders and mitochondria-related diseases. We are also developing biosensors for early diagnosis and intervention. The Steinmetz Cardiomyopathy Fund has been established to support this research.
Genome Regulation: We characterize and quantify transcriptome architecture using single-cell omics technologies. In particular, we are mapping enhancers to target genes in human cells using technologies developed in our lab. We are also interested in the function and regulation of splicing, non-coding RNAs, antisense transcription, and transcriptional heterogeneity.
Synthetic Biology: We are exploring the frontiers of DNA synthesis and synthetic biology. Using synthetic mitochondria or the first eukaryotic synthetic genome (Sc2.0), this work aims to enhance our understanding of genome architecture and transcriptional mechanisms, and to explore the potential of genome re-engineering.
Quantitative Genetics: We use functional genomics to study how genetics and environment interact and influence complex, polygenic traits. Our methods include genome-wide CRISPR editing screens and high-throughput analysis, aiding in understanding genetic diversity and developing predictive models linking genotype to phenotype. This also helps in identifying key genes for influencing phenotypic traits.
Genomics Technologies: As the basis for all our research, we are passionate about developing genomic technologies which increase the scale of biological questions that we can tackle. We’ve led innovations in therapeutic CRISPR genome editing, image-enabled cell sorting-based genetic screening, and single-cell multi-omics analyses, making them more efficient and suitable for complex eukaryotic genomes.
Future Goals
Our ultimate goal is to transform biomedical research to cure and prevent inherited diseases. We are dedicated to constant innovation in genomic technologies, which will help us achieve our goals more effectively. Our future plans include developing more precise genome editing tools, expanding functional genomics assays, mastering genome creation, and understanding disease causes. We aim for our work to have far-reaching implications, from advancing precision medicine to understanding the adaptability of natural populations to environmental changes.
