Dale Cowley, PhD

Research Interests

Keywords: Transgenic Mice, Transgenic Rats, CRISPR, Cas9, Genome Editing, Animal Models of Human Disease, Assisted Reproductive Technology

Animal Models Core

I am interested in the development and optimization of genome engineering tools for production of animal and cell line models to study gene function and human disease mechanisms. I direct the UNC Animal Models Core Facility where we use transgenic and genome editing technologies including CRISPR/Cas9, embryo microinjection and ES cell gene targeting approaches to produce genetically engineered models. We also have extensive expertise in molecular and cellular biology techniques such as CRISPR guide RNA design, production and validation, construct design, plasmid cloning, mutagenesis, BAC recombineering, and embryonic stem cell and iPS cell culture. These technologies allow us to offer a full range of services to facilitate projects for our clients. Assisted reproductive technologies including sperm and embryo cryopreservation, in vitro fertilization and strain rederivation are employed to assist clients in securing and sharing valuable rodent strains.

A major focus of our work is to improve efficiencies and expand capabilities in genome engineering and related technologies. We have an excellent track record in using CRISPR/Cas9 in mouse and rat embryos to successfully generate mouse and rat models with a variety of genome modifications. The creation of gene knockouts, point mutations and insertion of tags, reporter genes or other sequences up to around 6 kb is now accomplished routinely with reasonable efficiency. We are working to improve the efficiency of larger gene insertion and replacement technologies, especially as related to production of mouse and rat models with human genes replacing the rodent counterparts. These “humanized” models are an important resource for investigators studying human disease mechanisms and therapeutic agents that have specificity for the human version of the protein. We have also collaborated with clients to implement CRISPR/Cas9 genome editing in several previously untested mouse and rat strains such as Collaborative Cross inbred strains, NOD-Rag1KO-Il2rgKO (NRG) immunodeficient strain, SKH1 hairless mice and Zucker Diabetic Fatty (ZDF) rats. Our goal is to be able to introduce any desired genome modification in any desired mouse or rat strain to produce the best model for answering the research questions at hand.

Mentor Training:

 

Publications

• PubMed

Dale Cowley in UNC Genetics News