Supporting Cancer Research as a Core-based Scientist by Providing Comprehensive Genetically Engineered Rodent Model Services

Project Summary/Abstract To conquer cancer, researchers with diverse backgrounds and expertise must work together to discover molecular targets and develop therapeutics. Many investigators are unable to accomplish their research goals without access to specialized expertise, sophisticated technologies, and/or expensive instrumentation that are

impossible to master or operate in their own labs. The members of the P30CA125123 grant-supported Dan L Duncan Comprehensive Cancer Center (DLDCCC) at BCM are funded with more than $180M cancer research grants with over $41M NCI grants (direct costs). Dr. Reddy, a highly accomplished cancer physician scientist, is

the Program Director of the P30 grant, the director of the DLDCCC, and the Unit Director of this R50 application. As a Genetically Engineered Rodent Models (GERM) core-based non-tenure track research specialist (RS) and the Technical Director of the GERM core, I devote >70% of my effort to play an irreplaceable role in providing

comprehensive mouse cancer model services to these NCI-funded cancer research programs with my specialty and our GERM core’s state-of-the-art equipment. These services include: generation of various genetically engineered mouse (GEM) models by the CRISPR/Cas9 system using zygotes, the gene-targeting system using

embryonic stem (ES) cells, or the microinjection of transgenes into zygotes; in vitro fertilization and embryo transfer to rederive and/or quickly expand GEM models; cryopreservation of sperm and embryos for long-term storage of GEM lines; and genotype analysis of GEM lines. In the past 5-years, I and my team members have

generated 1653 knockout, knock-in and transgenic GEM models, many of which are essential for the success of many NCI-funded cancer research programs. I am a highly experienced cancer researcher who has published over 80 manuscripts. I have mastered methodologies and hold specialized expertise necessary for mouse and

rat embryo manipulation and genome engineering. I am a core leader who has contributed significantly to NCI- funded cancer research programs led by other investigators. Funding of this R50 application will provide me with a higher degree of autonomy to develop new technologies and services. In collaboration with investigators, I will

develop new embryo manipulation and genome editing systems for rat and Nile rat, as well as new genome- editing methods/strategies for mouse, such as prime editing to minimize off-targeting events, and approaches to increase conditional allele production efficiency and conditionally express disease-associated variants. I will

implement these new systems and technologies into our core services to better serve cancer researchers with novel rodent cancer models. With the R50 support, I will update my knowledge and ensure the usage of the best genome-editing system and methodology to generate rodent models by attending meetings and interacting with

other leaders in the field. My goal is to make our GERM core fully capable of providing comprehensive services of mouse, rat and Nile rat cancer models to support cancer research, and develop my career into an internationally recognized RS in the field of rodent genome editing and rodent cancer models.