Genome Engineering & Stem Cell Center (GESC)

The Genome Engineering & Stem Cell Center (GESC) Shared Resource was established by the Department of Genetics with support from Siteman Cancer Center (SCC) to facilitate functional genomic studies through the use of patient-derived iPSCs and the generation of genome modified cancer and iPSC cells and organisms using programmable nuclease technologies. The GESC has proven itself in the past five years to be critical to the success of SCC members and other Washington University (WU) investigators. The GESC provides both a one-stop shop and a la carte types of services, ranging from simple consultation, whereby SCC investigators are able to query experts in genomic engineering technologies and in generation and differentiation of patient derived induced pluripotent stem cells (iPSCs), to all-inclusive creation of cell and mouse models. The GESC’s accumulated experience and expertise enable the rapid creation of precise disease models using the most up-to-date technologies and will continue to be an invaluable asset to the next phase for deciphering cancer biology wherein large numbers of genomic variants identified in tumor sequencing projects must be evaluated for their functional significance in tumor growth, metastasis, and response to therapy.

Aim 1: Continue to optimize workflows and improve efficiencies on existing core services around cancer and iPS cell line engineering and animal model creation as well as iPSC reprogramming and differentiation. The rapid development in both genome engineering and iPSC fields offers much promise for cancer modeling. As a centered group with know-how in both areas and a strong focus on keeping up and developing technologies, the GESC has been an advantage that SCC investigators enjoyed in the past five years. In the next project period, we will optimize and improve efficiencies in both genome engineering and iPSC fronts; increase the level of automation for cost savings, reproducibility, reliability, and shortened delivery time for gene editing, iPSC reprogram and differentiation; test new CRISPR systems, Cas9 variants with higher specificity and alternative PAM sites; continuously evolve base editors and design; and carry out more diverse CRISPR screens.

Aim 2: Establish a disease-relevant and healthy control iPSCs repository for resource sharing at SCC, WU, and beyond. We will establish a panel of healthy control iPSC lines of diverse ethnic backgrounds with whole genome sequencing and epigenetic characterization, which is currently lacking in the field. In addition, we plan to help store and distribute all the iPSC lines we reprogrammed and engineered, with the potential to take on new lines we did not work with in the past. When surveyed, most of our customers were willing to deposit their published iPSCs to a repository for distribution to other researchers and indicated interest in using available iPSCs. We are currently gaining experience from managing a small repository for the Rebuilding a Kidney Consortium.

Aim 3: Develop new services to expand cellular disease modeling. With this aim, the new services under development will improve physiological relevance and speed in generation of cellular cancer models. First, we will focus on reversible immortalization, a method to temporarily turn on proliferation capability in terminally differentiated cells to obtain the desired cell number. The amplified cells presumably maintain the characteristics of primary cells, enabling large scale studies and long term use and even genetic manipulation. Second, we will introduce SNPs in patient primary cells at the time of reprogramming to shorten the timeline for generation isogenic pairs of patient-derived iPSCs. Finally, protocols for differentiating iPSCs into new cell types will be established to maximize the value of personalized iPSCs in drug and therapy screening. Our goal is to provide investigators more versatile cellular tools.

LOCATION: 4515 McKinley Building

PRICING: Please contact the core for current pricing of services offered.

TO ACCESS: Xiaoxia Cui at [email protected], 314-362-2906

NIH PUBLIC ACCESS POLICY: As of April 7, 2008, the NIH requires investigators with a publication using Siteman (or other NIH-funded) shared resources to submit (or have submitted for them) their final, peer reviewed manuscripts to PubMed Central(PMC) upon acceptance of publication, to be made publicly available within 12 months of publication. Many journals automatically submit these for authors, but Washington University also has assistance available through the Becker Medical Library. Please see,upon%20acceptance%20of%20the%20publication for more information.

PUBLICATION ACKNOWLEDGEMENT: If research supported by the Genome Engineering & Stem Cell Center results in publication, please acknowledge this support by including the following in your publication(s):

We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO., for the use of the Genome Engineering & Stem Cell Center, which provided __________ service. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant #P30 CA091842.