J. Keith Joung, MD, PhD
Associate Professor of Pathology
Harvard Medical School
Associate Chief for Research
The Jim and Ann Orr MGH Research Scholar
Massachusetts General Hospital, Pathology
The Joung Laboratory develops technologies for genome engineering using artificial "designer" DNA-binding domains. We utilize engineered zinc finger, transcription activator-like effector (TALE), and RNA-guided CRISPR/Cas-based systems to direct specific genomic alterations in living cells and organisms. In addition to developing and optimizing these technologies, we are exploring their applications for biological research and gene therapy.
Our laboratory develops robust protein engineering methods for constructing artificial designer DNA-binding domains. Our efforts focus on Cys2His2 zinc fingers and Xanthamonas transcriptional activator-like effector (TALE) repeats, two motifs that can be used to create proteins with customized DNA-binding specificities. We are also exploring the applications of engineered zinc finger and TALE repeat proteins for biological research and gene therapy.
Structures of TAL effector repeat
domains for binding each of the
four DNA bases overlaid on FISH
images of cells modified by
Engineering "designer" zinc fingers with novel DNA-binding specificities
The Joung lab is a founding member of The Zinc Finger Consortium. As part of this collaborative effort, we are developing robust selection and design methods for rapidly engineering synthetic zinc finger domains with novel, defined DNA-binding specificities. Designer zinc fingers can be used to target functional domains to specific genomic loci in cells (see below) and analysis of the amino acid sequences and specificities of these artificial fingers will be useful for developing algorithms to predict the DNA-binding specificities of naturally occurring zinc finger domains.
Engineered zinc finger nucleases for targeted, highly efficient genome manipulation
Zinc finger nucleases (ZFNs), consisting of designer zinc fingers fused to a non-specific endonuclease domain, can be used to introduce targeted DNA alterations with high efficiency at specific genomic loci in mammalian, plant, zebrafish, or Drosophila cells. These alterations result from repair of ZFN-induced double-stranded DNA breaks by normal cellular repair processes (non-homologous end-joining or homologous recombination). Ongoing projects in the lab are aimed at developing the ZFN genome modification methodology and using it for applications in biological research and gene therapy.
Altering cellular phenotypes using combinatorial zinc finger transcription factor librariesStructures of TAL effector repeat domains for binding each of the four DNA bases overlaid on FISH images of cells modified by gene-editing nucleases.
We have recently constructed large combinatorial libraries of zinc finger domains which can be fused to various transcriptional regulatory domains (e.g., activation or repression domains). We are introducing these libraries into human cells to induce specific desired phenotypes and cellular states.
For the first year of the MGH Research Scholars Awards program, three of the five Scholars are members of MGH-HMS Pathology and the MGH Cancer Center.
MGH Hotline 6.10.11 Selected from among 115 applications from across the MGH research community, the inaugural MGH Research Scholars recently were announced at the annual meeting of the MGH Research Advisory Council (RAC).