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
Rutherford, Sarah C; Fachel, Angela A; Li, Sheng et al. (2018) Extracellular vesicles in DLBCL provide abundant clues to aberrant transcriptional programming and genomic alterations. Blood 132:e13-e23
Barthel, Floris P; Wesseling, Pieter; Verhaak, Roel G W (2018) Reconstructing the molecular life history of gliomas. Acta Neuropathol 135:649-670
Kim, Hyunsoo; Kumar, Pooja; Menghi, Francesca et al. (2018) High-resolution deconstruction of evolution induced by chemotherapy treatments in breast cancer xenografts. Sci Rep 8:17937
Winer, Benjamin Y; Shirvani-Dastgerdi, Elham; Bram, Yaron et al. (2018) Preclinical assessment of antiviral combination therapy in a genetically humanized mouse model for hepatitis delta virus infection. Sci Transl Med 10:
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Schechter, Lisa M; Creely, David P; Garner, Cherilyn D et al. (2018) Extensive Gene Amplification as a Mechanism for Piperacillin-Tazobactam Resistance in Escherichia coli. MBio 9:
Tarchini, Basile; Longo-Guess, Chantal; Tian, Cong et al. (2018) A spontaneous mouse deletion in Mctp1 uncovers a long-range cis-regulatory region crucial for NR2F1 function during inner ear development. Dev Biol 443:153-164
Vian, Laura; P?kowska, Aleksandra; Rao, Suhas S P et al. (2018) The Energetics and Physiological Impact of Cohesin Extrusion. Cell 173:1165-1178.e20
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Garrett, Andrew M; Khalil, Andre; Walton, David O et al. (2018) DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members. Proc Natl Acad Sci U S A 115:E10216-E10224

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