?Transgenic Gene Knockout Shared Resource Genetically modified mice are invaluable for SJCCC researchers to evaluate gene function in vivo and determine how specific genes regulate cell growth and differentiation in normal and tumor tissue. The Transgenic Gene Knockout Shared Resource (TGKSR) centralizes services for the generation of genetically modified mice and provides education, expertise, and cost effectiveness that would be extremely difficult to maintain in individual laboratories. The TGKSR Director is Hartmut Berns, PhD, an expert in transgenic technology with 23 years' experience creating genetically engineered mice, 16 years thereof in the management of transgenic cores at Comprehensive Cancer Centers. He is supported by 5 full-time technologists who employ state-of-the-art gene- modification technologies to produce transgenic mice by pronucleus injection of DNA into zygotes, ESC-based gene-targeted mice by injection of genetically engineered ESCs into blastocyst-staged embryos, and gene- edited mice. Engineered mice are also generated by injection of the endonucleases TALEN or CRISPR/Cas9 into the pronucleus or cytoplasm of zygotes to produce gene KOs, knock-ins (KIs), conditional genes, or point mutations. There has been marked impact of the TGKSR on the science of SJCCC members. Researchers have gained insights from germline-transmitting chimeras of 41 different ESC-based targeted genes, and multiple founders of 34 DNA constructs during the current funding cycle. The TGKSR was used by 18 investigators of whom 83% (n=15/18) are members of the Cancer Center. Of these, 93% (n=14/15) hold cancer- focused peer-reviewed grants. These SJCCC members were drawn from 4 of 5 SJCCC Programs and yielded a combined total of 57 publications from CBP (n=26), NBTP (n=22), HMP (n=13), and DBSTP (n=1). During the upcoming cycle, in recognition of the growing impact of CRISPR/Cas9 reagents on advancing research performed by the SJCCC, the TGKSR will further enhance interactions with the new Center for Advanced Genome Engineering (CAGE) Shared Resource. We will create standardized workflows for bringing reagents designed by CAGE into the TGKSR and, in turn, for validating GEM tissue samples by CAGE in order to optimize GEM production. We will carry out pilot projects to test reagent modifications and concentrations to identify the most efficient and effective CRISPR approaches by comparing the efficiencies of pronuclear injections and cytoplasmic injections in zygotes. Our goal is to optimize these new reagents and their application in zygotes (to generate KOs, small KIs, point mutations, conditional alleles) and in ESCs (to generate large KIs and more involved conditional and inducible alleles) to most efficiently provide GEM to SJCCC members. Additionally, microinjection, surgery, and animal rooms of the TGKSR are slated to move to a new vivarium to be constructed on the St. Jude campus, with ground-breaking slated for spring 2018 and opening for 2021. Thorough planning of the scope and size of microinjection capabilities and animal space has been initiated to ensure that the future needs of SJCCC members for GEM production are met.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
Project #
Application #
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
St. Jude Children's Research Hospital
United States
Zip Code
Fuentes-Alabi, Soad; Bhakta, Nickhill; Vasquez, Roberto Franklin et al. (2018) The cost and cost-effectiveness of childhood cancer treatment in El Salvador, Central America: A report from the Childhood Cancer 2030 Network. Cancer 124:391-397
Wang, Xusheng; Jones, Drew R; Shaw, Timothy I et al. (2018) Target-Decoy-Based False Discovery Rate Estimation for Large-Scale Metabolite Identification. J Proteome Res 17:2328-2334
Sabin, N D; Cheung, Y T; Reddick, W E et al. (2018) The Impact of Persistent Leukoencephalopathy on Brain White Matter Microstructure in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Chemotherapy Only. AJNR Am J Neuroradiol 39:1919-1925
Brinkman, Tara M; Recklitis, Christopher J; Michel, Gisela et al. (2018) Psychological Symptoms, Social Outcomes, Socioeconomic Attainment, and Health Behaviors Among Survivors of Childhood Cancer: Current State of the Literature. J Clin Oncol 36:2190-2197
Follis, Ariele Viacava; Llambi, Fabien; Kalkavan, Halime et al. (2018) Regulation of apoptosis by an intrinsically disordered region of Bcl-xL. Nat Chem Biol 14:458-465
Bouchard, Jill J; Otero, Joel H; Scott, Daniel C et al. (2018) Cancer Mutations of the Tumor Suppressor SPOP Disrupt the Formation of Active, Phase-Separated Compartments. Mol Cell 72:19-36.e8
Flerlage, Jamie E; Metzger, Monika L; Bhakta, Nickhill (2018) The management of Hodgkin lymphoma in adolescents and young adults: burden of disease or burden of choice? Blood 132:376-384
Hijano, Diego R; Siefker, David T; Shrestha, Bishwas et al. (2018) Type I Interferon Potentiates IgA Immunity to Respiratory Syncytial Virus Infection During Infancy. Sci Rep 8:11034
Zheng, Daniel J; Krull, Kevin R; Chen, Yan et al. (2018) Long-term psychological and educational outcomes for survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study. Cancer 124:3220-3230
Fatima, Soghra; Zhou, Sheng; Sorrentino, Brian P (2018) Marking of definitive HSC precursors in E7.5-E8.5 embryos using an Abcg2-CreER lineage-tracing mouse model. Exp Hematol 65:29-33

Showing the most recent 10 out of 6764 publications