The overall scientific goal of the Growth Control and Genomic Stability Program is to understand mechanisms of proliferation, transcriptional regulation of oncogenic signaling pathways, DNA damage response and checkpoint activation, maintenance of genomic integrity and telomere function, and how these processes are disrupted or altered in cancer cells. Genomic instability is one of the key contributors to cancer progression and the genesis of tumor heterogeneity, and can engender either sensitivity or resistance to targeted and dastogenic cancer therapies. The members of this program study diverse aspects of how normal somatic cells, stem cells, and cancer cells respond to DNA damage, maintain genomic integrity, and respond to traditional and targeted chemotherapies. The functions of p53 in cell cycle checkpoint control and in diverse stress responses, and the use of adenovirus early proteins to interrogate cell signaling pathways and p53 checkpoint signaling comprise areas of significant focus of the program with opportunities for clinical translation. Chemical genetics is being used to study cellular signaling pathways that drive cancer cell proliferation. Other important topics include molecular mechanisms of transcriptional regulation of oncogenic pathways and of tumor suppressor gene expression, how nuclear pore subunits regulate gene expression, and the relationship of fetal mammary stem cells to stem-like cells in breast cancer. The program includes nine members from five different Laboratories (Departments), see the following page for a list of personnel. The NCI and other peer-reviewed cancer related support (direct costs) for the last budget year was $3,049,383. The substantial NIH and other federal support for this program is outlined in the table of externally funded research projects. The total number of cancer-relevant publications by members of this program in the last grant period (2008- 2012) was 132. Of the total publications, 1% were intraprogrammatic and 13% were interprogrammatic.

Public Health Relevance

The major hallmark of cancer is loss of the control of cell growth. This program will study the mechanisms by which cancer cells lose control, focusing in particular on mechanisms of controlling the stability of the cell genome.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA014195-41
Application #
8934261
Study Section
Subcommittee G - Education (NCI)
Program Officer
Ciolino, Henry P
Project Start
2013-12-01
Project End
2018-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
41
Fiscal Year
2014
Total Cost
$39,041
Indirect Cost
$19,055
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Liu, Wen-Hsien; Kang, Seung Goo; Huang, Zhe et al. (2016) A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells. J Exp Med 213:1901-19
Xu, Jiqing; de Winter, Fred; Farrokhi, Catherine et al. (2016) Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer's disease model. Sci Rep 6:31692
Ibarra, Arkaitz; Benner, Chris; Tyagi, Swati et al. (2016) Nucleoporin-mediated regulation of cell identity genes. Genes Dev 30:2253-2258
Chinen, Takatoshi; Kannan, Arun K; Levine, Andrew G et al. (2016) An essential role for the IL-2 receptor in Treg cell function. Nat Immunol 17:1322-1333

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