During the past decade, genetically modified mice have increasingly been a source of many new cancer models that have helped elucidate pathways contributing to tumor development and progression. With the completion of the human and mouse genome sequences and the initiation of large-scale efforts to functionally annotate these genomes, this trend continues to accelerate. Production of genetically modified mice requires highly specialized instrumentation and expertise not available in most labs. The mission of the Gene Targeting and Transgenic Shared Resource (GTTR) is to ensure that investigators have access to state-of-the-art transgenic mouse technologies, methods and animal models. The Resource Director and Assistant Director provide guidance to investigators from the earliest planning stages of the project when constructs are designed to advanced stages of the project during phenotype analysis. Resource technicians perform the specialized ES cell and embryo manipulation methods to generate the genetically modified mice. During the past fourteen years, the Facility has provided over 700 new genetically modified lines. Shared Resource staff have generated mutant mice on multiple strain backgrounds, generated 200 knockouts and 520 transgenics (including BACs) from 165 constructs for the six CCSG Programs. GTTR has also assisted in the development of unique mouse models that contribute to understanding imprinting and its role in cancer, regulation of important genes and two transgenic models that mimic chromosome rearrangements associated with specific human cancers. Use of the Resource has continued to increase with the ongoing recruitment into the Genetics, Cell Stress and Biophysical Therapies, Genitourinary Cancers and Experimental Therapeutics Programs. Projects requiring the development of transgenic mouse models are becoming increasingly relevant to validate in vitro findings, especially in light of high-throughput clinical-based findings. As such, the GTTR has been seeing an increasing trend in the use of the Resource by clinical researchers as well as basic scientists. First priority for use is given to peer-review-funded CCSG members;second to non-peer-review-funded CCSG members;third to non-members and academic collaborators;and last priority to external users. During the reporting period, the Gene Targeting and Transgenic Shared Resource has served 28 members from 5 research programs, with 15% utilization by CCSG members with peer reviewed funding. The CCSG support provides 11% of the overall proposed budget.

Public Health Relevance

Genetically modified mice are critical to elucidate pathways contributing to tumor development and progression and validate in vitro findings. The Gene Targeting and Transgenic Shared Resource provides access to specialized technologies, services, and expertise that enhance scientific interaction and productivity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA016056-37
Application #
8738370
Study Section
Subcommittee G - Education (NCI)
Project Start
1997-06-16
Project End
2019-04-30
Budget Start
2014-06-26
Budget End
2015-04-30
Support Year
37
Fiscal Year
2014
Total Cost
$44,169
Indirect Cost
$17,471
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Ciamporcero, Eric; Miles, Kiersten Marie; Adelaiye, Remi et al. (2015) Combination strategy targeting VEGF and HGF/c-met in human renal cell carcinoma models. Mol Cancer Ther 14:101-10
Ma, Yingyu; Hu, Qiang; Luo, Wei et al. (2015) 1?,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells. J Steroid Biochem Mol Biol 148:166-71
Shen, Li; Sundstedt, Anette; Ciesielski, Michael et al. (2015) Tasquinimod modulates suppressive myeloid cells and enhances cancer immunotherapies in murine models. Cancer Immunol Res 3:136-48
Adelaiye, Remi; Ciamporcero, Eric; Miles, Kiersten Marie et al. (2015) Sunitinib dose escalation overcomes transient resistance in clear cell renal cell carcinoma and is associated with epigenetic modifications. Mol Cancer Ther 14:513-22
Ambrosone, Christine B; Zirpoli, Gary; Ruszczyk, Melanie et al. (2014) Parity and breastfeeding among African-American women: differential effects on breast cancer risk by estrogen receptor status in the Women's Circle of Health Study. Cancer Causes Control 25:259-65
Uekusa, Shota; Kawashima, Hiroyuki; Sugito, Kiminobu et al. (2014) Nr4a3, a possibile oncogenic factor for neuroblastoma associated with CpGi methylation within the third exon. Int J Oncol 44:1669-77
Rohrbach, Daniel J; Muffoletto, Daniel; Huihui, Jonathan et al. (2014) Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging. Acad Radiol 21:263-70
Röhm, Marc; Grimm, Melissa J; D'Auria, Anthony C et al. (2014) NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis. Infect Immun 82:1766-77
Haller, Andrew C; Tan, Wei; Payne-Ondracek, Rochelle et al. (2014) High SPDEF may identify patients who will have a prolonged response to androgen deprivation therapy. Prostate 74:509-19
Ambrosone, Christine B; Young, Allyson C; Sucheston, Lara E et al. (2014) Genome-wide methylation patterns provide insight into differences in breast tumor biology between American women of African and European ancestry. Oncotarget 5:237-48

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