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.
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.
|Aslanian, Aaron; Yates 3rd, John R; Hunter, Tony (2014) Mass spectrometry-based quantification of the cellular response to methyl methanesulfonate treatment in human cells. DNA Repair (Amst) 15:29-38|
|Lew, Erin D; Oh, Jennifer; Burrola, Patrick G et al. (2014) Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities. Elife 3:|
|Chaix, Amandine; Zarrinpar, Amir; Miu, Phuong et al. (2014) Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab 20:991-1005|
|Xia, Yifeng; Shen, Shen; Verma, Inder M (2014) NF-?B, an active player in human cancers. Cancer Immunol Res 2:823-30|
|Islam, Md Soriful; Catherino, William H; Protic, Olga et al. (2014) Role of activin-A and myostatin and their signaling pathway in human myometrial and leiomyoma cell function. J Clin Endocrinol Metab 99:E775-85|
|Evans, Ronald M; Mangelsdorf, David J (2014) Nuclear Receptors, RXR, and the Big Bang. Cell 157:255-66|
|Liu, Guang-Hui; Suzuki, Keiichiro; Li, Mo et al. (2014) Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs. Nat Commun 5:4330|
|Buchwalter, Abigail L; Liang, Yun; Hetzer, Martin W (2014) Nup50 is required for cell differentiation and exhibits transcription-dependent dynamics. Mol Biol Cell 25:2472-84|
|Hatori, Megumi; Gill, Shubhroz; Mure, Ludovic S et al. (2014) Lhx1 maintains synchrony among circadian oscillator neurons of the SCN. Elife 3:e03357|
|Korf, Katharina; Wodrich, Harald; Haschke, Alexander et al. (2014) The PML domain of PML-RAR? blocks senescence to promote leukemia. Proc Natl Acad Sci U S A 111:12133-8|
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