George Dieter is a prominent figure in the fields of genomics and precision health. His research focuses on understanding how genetic variation influences phenotypic diversity and disease, utilizing cutting-edge genomics technologies and approaches. Dieter's work spans from fundamental research to translational applications, aiming to transform biomedical research and ultimately cure and prevent inherited diseases.
Education and Early Career
Dieter's academic journey began with a B.S. in Molecular Biophysics and Biochemistry from Yale University (1994-1997). He then pursued a Ph.D. in Genetics at Stanford University (1997-2001), where he was advised by Ronald W. His educational background provided him with a strong foundation in molecular biology and genetics, setting the stage for his future research endeavors.
Current Research Focus
Dieter's current research is driven by the challenge of understanding how genetic variation shapes cellular phenotypes and the complex interplay between genetic variants and environmental factors. His lab develops genomics technologies and approaches to study the molecular processes underlying complex genetic traits, gene regulation, and inherited diseases. The research is multi-faceted, incorporating both experimental and computational approaches.
Precision Health
In the realm of precision health, Dieter's team uses model organisms, including induced pluripotent stem cells, mice, and humans, to study genetic and cellular mechanisms in diseases and to evaluate potential treatments. They apply genome analysis and CRISPR editing to study human diseases such as dilated cardiomyopathy, immune disorders, and mitochondria-related diseases. Additionally, they are developing biosensors for early diagnosis and intervention. The Steinmetz Cardiomyopathy Fund supports this research.
One notable project is the development of Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a scalable platform producing autologous organotypic iPS cell-derived induced skin composite (iSC) grafts for definitive treatment. The clinical-grade manufacturing process integrates CRISPR-mediated genetic correction with reprogramming into one step, accelerating the derivation of COL7A1-edited iPS cells from patients.
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Genome Regulation
Dieter's lab characterizes and quantifies transcriptome architecture using single-cell omics technologies. They are mapping enhancers to target genes in human cells using technologies developed in their lab. Their interests also include the function and regulation of splicing, non-coding RNAs, antisense transcription, and transcriptional heterogeneity.
Synthetic Biology
Exploring the frontiers of DNA synthesis and synthetic biology, Dieter's team uses synthetic mitochondria or the first eukaryotic synthetic genome (Sc2.0) to enhance our understanding of genome architecture and transcriptional mechanisms. This work also explores the potential of genome re-engineering.
Quantitative Genetics
Functional genomics is used to study how genetics and environment interact and influence complex, polygenic traits. 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 approach also helps in identifying key genes for influencing phenotypic traits.
Genomics Technologies
Dieter is passionate about developing genomic technologies that increase the scale of biological questions that can be tackled. His lab has 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.
One example of their work in this area is the development of MAGESTIC 3.0, a templated CRISPR editing system for installing natural variants genome-wide in budding yeast. This system was used to dissect causal variants residing in 112 quantitative trait loci across 32 environmental conditions, revealing an enrichment for missense variants and loci with multiple causal variants.
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Future Goals
Dieter's ultimate goal is to transform biomedical research to cure and prevent inherited diseases. He is dedicated to constant innovation in genomic technologies, including developing more precise genome editing tools, expanding functional genomics assays, mastering genome creation, and understanding disease causes.
Selected Publications
Dieter's research has been published in numerous high-impact journals. Some notable publications include:
- Neumayer, G., et al. (2022). Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a scalable platform producing autologous organotypic iPS cell-derived induced skin composite (iSC) grafts for definitive treatment.
- Hale, J. J., et al. (2021). Interactions between genetic perturbations and segregating loci can cause perturbations to show different phenotypic effects across genetically distinct individuals.
- Lattmann, E., et al. (2021). SEC-DIA-MS couples size-exclusion chromatography to EV concentration and deep-proteomic profiling using data-independent acquisition.
- Roy, K. R., et al. (2020). MAGESTIC 3.0: A highly efficient system for genome-wide installation of natural variants in budding yeast.
- Gschwind, A. R., et al. (2021). Identifying transcriptional enhancers and their target genes is essential for understanding gene regulation and the impact of human genetic variation on disease.
- McCulloch, L. H., et al. (2015). Synthesis, assembly, and characterization of a synthetic chromosome.
- Schindler, D., et al. (2014). Design, construction, and validation of a fully synthetic yeast chromosome.
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