The Tumor Development Program focuses on understanding the genetic, epigenetic and developmental processes that take place in tumor-initiating cells and tumor-susceptible tissues during tumor development. The Program was established in 2007 by combining the Oncodevelopmental Biology Program with the Cancer Genetics &Epigenetics Program. This merger logically combines expertise in developmental aspects of cancer with genetic and epigenetic mechanisms underiying cancer development. Drs. Robert Oshima and Manuel Perucho are co-Leaders of the Program, which consists of 14 full members and 2 adjunct members. The Program comprises three overarching themes, which benefit from highly interdisciplinary program membership, including expertise in genetic and epigenetic pathways, stem cell biology, mouse models of cancer and medicinal chemistry: 1- Genetic and epigenetic changes in cancer. Program members continue to lead the field of the """"""""mutator phenotype"""""""" and carcinogenesis, with additional strengths in the areas of chromatin modifications, cell cycle regulation and checkpoint signaling, and RNA biology;2- Stem cell biology, with focus of Notch and Wnt signaling, and mouse models of cancer, with focus on mammary gland and colon models. The Program is a resource for all CCSG Programs due to its expertise in mouse tumor models;and 3- Novel targets in cancer treatment, with focus on nuclear receptors and retinoic acids. Notably, members of the Program have developed a retinoid-like drug, Targretin?, which is FDA-approved for the treatment cutaneous T cell lymphoma. Members of this collaborative and multidisciplinary Program interact at a number of levels, including monthly faculty meetings and through collaborative grants. Program funding is currently at $12.9MM in annual total costs ($7.0MM direct). Program members participate in two POIs (1 from NCI), three U54/U19 grants, and 15 additional collaborative peer-reviewed federal and state grants. Program members also have 17 NIH ROIs (7 from NCI). The Program's productivity is further reflected by 345 publications since last review, and by 58 Program publications in 2008, which represent 14% of intra- and 21% of inter-programmatic collaborations, respectively.

Public Health Relevance

The Tumor Development Program tackles the fundamental causes underlying tumor inifiafion and development. Understanding the eariy genefic, epigenefic and developmental changes and defects that occur in tumor-initiating cells and tumor-susceptible tissues is expected to lead into novel therapies that target eariy stages of cancer, or key cell populations that continue to drive malignancy of late stage tumors.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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Sanford-Burnham Medical Research Institute
La Jolla
United States
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Fujita, Yu; Khateb, Ali; Li, Yan et al. (2018) Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines Intestinal Inflammation and Severity of Colitis. Cell Rep 24:3296-3311.e6
Scully, Kathleen M; Lahmy, Reyhaneh; Signaevskaia, Lia et al. (2018) E47 Governs the MYC-CDKN1B/p27KIP1-RB Network to Growth Arrest PDA Cells Independent of CDKN2A/p16INK4A and Wild-Type p53. Cell Mol Gastroenterol Hepatol 6:181-198
Borlido, Joana; Sakuma, Stephen; Raices, Marcela et al. (2018) Nuclear pore complex-mediated modulation of TCR signaling is required for naïve CD4+ T cell homeostasis. Nat Immunol 19:594-605
Follis, Ariele Viacava; Llambi, Fabien; Kalkavan, Halime et al. (2018) Regulation of apoptosis by an intrinsically disordered region of Bcl-xL. Nat Chem Biol 14:458-465
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Sun, Younguk; Chen, Bo-Rui; Deshpande, Aniruddha (2018) Epigenetic Regulators in the Development, Maintenance, and Therapeutic Targeting of Acute Myeloid Leukemia. Front Oncol 8:41
Ekanayake, Vindana; Nisan, Danielle; Ryzhov, Pavel et al. (2018) Lipoprotein Particle Formation by Proapoptotic tBid. Biophys J 115:533-542
Diez-Cuñado, Marta; Wei, Ke; Bushway, Paul J et al. (2018) miRNAs that Induce Human Cardiomyocyte Proliferation Converge on the Hippo Pathway. Cell Rep 23:2168-2174
Wang, Yang; Li, Yue; Yue, Minghui et al. (2018) N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci 21:195-206
Lundquist, Mark R; Goncalves, Marcus D; Loughran, Ryan M et al. (2018) Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy. Mol Cell 70:531-544.e9

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