The advent of genome engineering technologies, including the RNA-guided CRISPR/Cas9 system, has enabled the precise targeting of genomic locations with molecular machinery. While most widely used for editing DNA sequences, we believe these technologies can have even greater and broader impact by programming other functions at specific genomic locations. For example, we have adapted and applied these tools to robustly and precisely manipulate gene expression, program the epigenome, annotate the function of the non-coding genome, and control cell fate decisions. Specifically, we have engineered CRISPR/Cas9-based tools to regulate the expression of endogenous genes and applied these tools to control diverse genes relevant to disease, development, and differentiation. Genome-wide analysis of the DNA-binding, gene regulation, and chromatin remodeling by these targeted epigenome modifiers has demonstrated their exceptional specificity. We have applied these technologies to control the decisions of stem cells to become specific cell fates and reprogram cell types into other lineages for drug screening, disease modeling, and in vivo tissue regeneration. We have used in vivo epigenome editing to alter expression of genes associated with complex disease phenotypes. Genome-wide screens of epigenetic modulation of target gene expression have enabled the discovery of novel distal regulators of target gene expression and modulators of cell fate commitment. Collectively, these studies demonstrate the potential of modern genome engineering technologies to capitalize on the products of the Genomic Revolution and transform medicine, science, and biotechnology.
The Gersbach Lab is focused on engineering new methods for directing cell behavior to regenerate diseased or damaged tissues and treat genetic diseases. Their work capitalizes on the products of the Genomic Revolution and modern advances in the fields of genetic reprogramming, gene delivery, protein engineering, stem cell transplantation, and synthetic biology to create innovative biologic approaches to improving human health. These studies also facilitate a better understanding of complex processes including organogenesis, cell lineage determination, and gene regulation that will ultimately lead to improved design of drugs and biotherapeutics. Their efforts are catalyzed by interdisciplinary collaborations with investigators in engineering and medicine at Duke and other institutions.
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