RESEARCH PROGRAM The overarching goal of the JAX Cancer Center (JAXCC) Research Program, Genetic Models for Precision Cancer Medicine, is to advance the vision of precision oncology through basic research discoveries with potential for translational and clinical impact. Members use diverse, multi-scale strategies to deconvolute complex cancer systems to their principal components and to investigate the drivers of cancer cell complexity, tumor evolution, and tumor adaptation. Elucidating these fundamental biological processes are key to a principled, mechanistic understanding of the adverse effects of cancer therapy and of treatment resistance. During the current funding period we have expanded, and reshaped, the JAXCC into a new cancer research force with a focus on complex genetics and functional genomics. Research is organized around three complementary Specific Aims.
Aim 1 seeks to develop novel organismal, cellular, and computational models of cancer, drawing on the JAXCC's longstanding strengths in model development.
Aim 2 examines the genomic instability and genetic complexity of cancer and determines their functional consequences in the cancer cell. Using advanced computational methods and genomic technologies we will interrogate animal models developed in Aim 1 as well as patient samples.
Aim 3 investigates how key components of a tumor and the host contribute to cancer biology, examining the cancer cell intrinsic and extrinsic components of a malignant tumor. Results from studies in Aim 3, integrated with the genetic alterations identified in Aim 2 with models developed in Aim 1, will allow us to deconvolute the complex interactions of the tumor and host microenvironments. The 53 full program members of the JAXCC include 33 on the Bar Harbor campus and 20 on the Farmington campus. Through its emphasis on basic research, unique model development, and technological innovation, the program leverages funding from multiple NIH ICs in support of cancer-focused research. More recently, we brought our technologies into the clinical arena through collaborations with SWOG, the Maine Cancer Genomics Initiative, City of Hope, Beth Israel Deaconess Medical Center, University of Connecticut Health Center, and the Connecticut Children's Hospital. The program is supported by $10,401,511 direct costs in NCI and other peer- reviewed cancer-related grants in the last budget year. Over the last grant cycle, CCSG funds have supported 379 publications including 30% intra-programmatic collaborations and 72% with external collaborators. The efforts of the Co-Program Leaders, Drs. Karolina Palucka and Roel Verhaak, and JAXCC leadership have fostered interactivity among JAXCC members through regular Research Program meetings, subsidized travel between campuses, and the JAXCC Annual Retreat. The annual JAXCC Retreat and monthly program meetings are the primary forums that bring together Cancer Center members from both campuses to develop intra- programmatic collaborations and to participate in the planning for resource development and faculty recruitment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA034196-34
Application #
9854061
Study Section
Subcommittee H - Clinical Groups (NCI)
Project Start
Project End
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
34
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609
Cho, Sung-Yup; Sung, Chang Ohk; Chae, Jeesoo et al. (2018) Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments. Blood 131:1931-1941
Pullagura, Sri Ramulu N; Buaas, Bill; Gray, Nichelle et al. (2018) Functional Redundancy of DICER Cofactors TARBP2 and PRKRA During Murine Embryogenesis Does Not Involve miRNA Biogenesis. Genetics 208:1513-1522
Kong, Yang; Naggert, J├╝rgen K; Nishina, Patsy M (2018) The Impact of Adherens and Tight Junctions on Physiological Function and Pathological Changes in the Retina. Adv Exp Med Biol 1074:545-551
Chang, Bo; FitzMaurice, Bernard; Wang, Jieping et al. (2018) Spontaneous Posterior Segment Vascular Disease Phenotype of a Mouse Model, rnv3, Is Dependent on the Crb1rd8 Allele. Invest Ophthalmol Vis Sci 59:5127-5139
Sharma, Manju; Braun, Robert E (2018) Cyclical expression of GDNF is required for spermatogonial stem cell homeostasis. Development 145:
Shi, Jiayuan; Hua, Li; Harmer, Danielle et al. (2018) Cre Driver Mice Targeting Macrophages. Methods Mol Biol 1784:263-275
Johnson, Kenneth R; Gagnon, Leona H; Tian, Cong et al. (2018) Deletion of a Long-Range Dlx5 Enhancer Disrupts Inner Ear Development in Mice. Genetics 208:1165-1179
Hosur, Vishnu; Farley, Michelle L; Low, Benjamin E et al. (2018) RHBDF2-Regulated Growth Factor Signaling in a Rare Human Disease, Tylosis With Esophageal Cancer: What Can We Learn From Murine Models? Front Genet 9:233
Paigen, Kenneth; Petkov, Petko M (2018) PRDM9 and Its Role in Genetic Recombination. Trends Genet 34:291-300
Dominguez, Pilar M; Ghamlouch, Hussein; Rosikiewicz, Wojciech et al. (2018) TET2 Deficiency Causes Germinal Center Hyperplasia, Impairs Plasma Cell Differentiation, and Promotes B-cell Lymphomagenesis. Cancer Discov 8:1632-1653

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