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
Herzig, S├ębastien; Shaw, Reuben J (2018) AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 19:121-135
Sweeney, Lora B; Bikoff, Jay B; Gabitto, Mariano I et al. (2018) Origin and Segmental Diversity of Spinal Inhibitory Interneurons. Neuron 97:341-355.e3
Hartmann, Phillipp; Hochrath, Katrin; Horvath, Angela et al. (2018) Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice. Hepatology 67:2150-2166
Glustrom, Leslie W; Lyon, Kenneth R; Paschini, Margherita et al. (2018) Single-stranded telomere-binding protein employs a dual rheostat for binding affinity and specificity that drives function. Proc Natl Acad Sci U S A 115:10315-10320
Giraddi, Rajshekhar R; Chung, Chi-Yeh; Heinz, Richard E et al. (2018) Single-Cell Transcriptomes Distinguish Stem Cell State Changes and Lineage Specification Programs in Early Mammary Gland Development. Cell Rep 24:1653-1666.e7
Ma, Jiao; Saghatelian, Alan; Shokhirev, Maxim Nikolaievich (2018) The influence of transcript assembly on the proteogenomics discovery of microproteins. PLoS One 13:e0194518
Patriarchi, Tommaso; Cho, Jounhong Ryan; Merten, Katharina et al. (2018) Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science 360:
Kolar, Matthew J; Nelson, Andrew T; Chang, Tina et al. (2018) Faster Protocol for Endogenous Fatty Acid Esters of Hydroxy Fatty Acid (FAHFA) Measurements. Anal Chem 90:5358-5365
Ogawa, Junko; Pao, Gerald M; Shokhirev, Maxim N et al. (2018) Glioblastoma Model Using Human Cerebral Organoids. Cell Rep 23:1220-1229
Ahmadian, Maryam; Liu, Sihao; Reilly, Shannon M et al. (2018) ERR? Preserves Brown Fat Innate Thermogenic Activity. Cell Rep 22:2849-2859

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