System Genetics
and Precision Health
The Steinmetz lab develops innovative genomic technologies to study the genetic basis of complex phenotypes, the mechanisms of gene regulation, and the molecular systems underpinning disease. We’re leveraging biological insights across scales and organisms to predict, diagnose, treat and ultimately prevent disease.
Our Approach
Although advances in genomics have linked thousands of genetic variants to complex traits of health and disease, we still lack a comprehensive understanding of how genetic variation governs phenotypic diversity and disease.
This gap persists because genetic effects emerge through complex layers of molecular pathways – shaped by regulatory networks, interactions between variants and dynamic environmental influences that are difficult to untangle.
Our approach is to drive technology development together with biological application. We work across the broad axis of fundamental to translational research. We’re developing genomics technologies and approaches to study the molecular processes that govern complex genetic traits, gene regulation, and inherited diseases.
Our Research
Our research is multi-faceted, including experimental and computational approaches:
Genomics Technologies
Technology development underpins all of 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, enabling genomic discovery at unprecedented scale and efficiency in complex eukaryotic systems.
Precision Medicine
We engineer disease models ranging from induced pluripotent stem cells to mice and humans, to study genetic and cellular mechanisms driving diseases and evaluate potential treatments. Using genome analysis and CRISPR-based editing, we 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 our research on heart disease.
Genome Regulation
We define transcriptome architecture and its regulation using single-cell omics technologies. A major focus is 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 design. Using synthetic mitochondria or the first eukaryotic synthetic genome (Sc2.0), this work aims to enhance our understanding of genome architecture and transcriptional mechanisms, while establishing the foundation for large-scale 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 to understand genetic diversity and developing predictive models linking genotype to phenotype. This also helps in identifying key genes for influencing phenotypic traits.
Future Goals
Our goal is to transform biomedical research and make inherited diseases preventable – and ultimately curable. Along the way we strive for constant innovation: developing and improving genomic technologies to increase the scale of discovery and shorten the path from discovery to disease intervention. Our future plans include developing more precise genome editing tools, expanding the power of functional genomics assays, and mastering genome engineering. By uncovering the molecular basis of disease, we aim for our work to have far-reaching implications, from advancing precision medicine to understanding the adaptability of natural populations to environmental changes.
Lab Sites
The Steinmetz lab operates across three sites: the Department of Genetics at Stanford University School of Medicine, the Stanford Genome Technology Center (SGTC), and EMBL Heidelberg (Germany). At the SGTC, we develop single-cell approaches to precise genome engineering and off-target detection, as well as novel biosensors for detection of minute quantities of biological material. At EMBL Heidelberg, we focus on dilated cardiomyopathy and gene regulation.