Lester John and Lynne Dewar Lloyd Distinguished Professor Department of Bioengineering
The focus of my work is to establish reliable techniques that allow in vitro modeling of human diseases using genetically engineered human stem cell models. In order to facilitate such in vitro modeling I developed gene targeting techniques in human pluripotent stem cells. Unlike mouse embryonic stem cells, gene targeting of human cells by homologous recombination is inefficient whichhas impeded the use of human pluripotent stem cells for disease research. To overcome this limitation I have pioneered the use of site-specific nucleases to modify the genome of human cells. This technology allowed us to enhance genetargeting efficiency in human cells and establish GFP-knock-in reporter cell lines and an isogenic over-expression system using a “safe harbor locus”. We have established robust targeting protocols to generate pairs of human embryonic and induced pluripotent stem (iPS) cells that differ exclusively at one disease-relevant locus. We are currently employing state of the art genome editing tools to investigate the role of telomerase and telomere function in stem cells and during tumorigenesis. Furthermore, we apply these technologies to develop adult stem cell models for intestinal diseases.