I am an Early-Stage Investigator performing independent research at The Jackson Laboratory. My training and research accomplishments have provided me with the knowledge, research experience, and technical expertise to successfully complete the proposed project. During my Ph.D. program I gained expertise in microarrays, data analysis, real-time PCR, and gained a strong background in molecular biology techniques. As a post-doctoral fellow in the Shultz lab at The Jackson Laboratory (JAX), I gained skills in the development, phenotypic characterization, and use of humanized mouse models, patient-derived tumor xenograft (PDX) models, and thus a strong background in mouse genetics. Additionally, I have participated in weekly Genetics and Genomics interest group meetings at JAX to present my research findings. I have been involved in the development of novel tools and reagents for rapid generation of genetically modified mouse models on highly defined backgrounds using Zinc Finger Nucleases, TALENs, and CRISPR/Cas9, and Bxb1 systems. Specifically, I have identified that genes outsmart gene-targeting strategies to reinitiate transcription and translation. These tools have enabled examination of the link between the large coding and non-coding structural variants and other complex diseases in mice and genetically modified stem cells. In work particularly relevant to the proposed project, I have developed and characterized mouse models of human disease using CRISPR/Cas9. Additionally, I invented a one-step approach for rapid generation transgenic mice using the Cas9-Bxb1 toolbox. Also, I have developed a sequential one-cell/two-cell approach for floxing genes to enable rapid generation of conditional alleles.