The mission of the Molecular Oncology Program (MO) is to integrate and coordinate research with a focus on identifying and exploring anti-cancer targets, particularly those that distinguish cancer from noncancer cells based on growth, differentiation and survival. Key accomplishments in this Program include the discovery of a novel small molecule that targets an oncogenic fusion protein, STAG2 as a regulator of chromosomal integrity that is deleted in many cancers, and a novel method to chemically reprogram cancer cells. Continued emphasis is on discovering small molecule probes that may lead to future novel therapeutics and biomarkers. To accomplish this mission, MO members perform research around three themes: Theme 1 focuses on unique genomic events that initiate and sustain cancer growth: mechanisms deregulating chromosomal integrity and the role of oncogenic chromosomal translocations in malignancy. Theme 2 focuses on the immortal lives of cancer cells: studies on cellular immortalization;cancer prevention by dietary components that modulate DNA repair mechanisms;and the effect of nutrients on the activity of mutant p53 and its role in transcriptional activation in DNA repair. Theme 3 focuses on the metastatic mechanisms that allow the spread of cancer: discovering novel regulators of metastatic pathways and identifying useful small molecule inhibitors. Led by Jeffrey Toretsky, MD, and Vicente Notario, PhD, the Program has 17 members and includes faculty from six Georgetown University departments. Total peer review funding is $5.9M (direct) in the last budget year, of which $4M is from NCI. MO members published 210 peer-reviewed publications, of which 35% involved external collaborations and 41% were intra- and/or interprogrammatic, the latter involving collaborations with all three other LCCC Programs. Research on small molecules targeting EWS-FLH and the conditionally reprogrammed cells methodology begun in MO have transitioned to the Experimental Therapeutics or Breast Cancer Programs for clinical trials. Members used all nine Shared Resources;MO research on cell immortalization was developed into a new shared service by the Center. The Cancer Center has added value to the Program through $16M in institutional support over the past funding period facilitating the recruitment and support of two new junior faculty members, by facilitating access to new technologies both within the Cancer Center or through external affiliations with other institutions.

Public Health Relevance

): While the Program is neither disease-specific nor therapy-focused, it develops the basic scientific underpinnings for prevention and targeted therapies across all cancer types. For example, prostate cancer and the human papilloma virus (HPV) are major areas of emphasis investigated by MO researchers that have important regional implications due to the high rate of prostate cancer and HPV infection in our catchment area.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA051008-21
Application #
8698913
Study Section
Subcommittee G - Education (NCI)
Project Start
1997-08-15
Project End
2019-04-30
Budget Start
2014-09-09
Budget End
2015-04-30
Support Year
21
Fiscal Year
2014
Total Cost
$38,982
Indirect Cost
$13,913
Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Lai, Chih-Hsin; Lai, Ying-Jung J; Chou, Feng-Pai et al. (2016) Matriptase Complexes and Prostasin Complexes with HAI-1 and HAI-2 in Human Milk: Significant Proteolysis in Lactation. PLoS One 11:e0152904
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Hunegnaw, Ruth; Vassylyeva, Marina; Dubrovsky, Larisa et al. (2016) Interaction Between HIV-1 Nef and Calnexin: From Modeling to Small Molecule Inhibitors Reversing HIV-Induced Lipid Accumulation. Arterioscler Thromb Vasc Biol 36:1758-71
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Allen, Megan; Ghosh, Suhasini; Ahern, Gerard P et al. (2016) Protease induced plasticity: matrix metalloproteinase-1 promotes neurostructural changes through activation of protease activated receptor 1. Sci Rep 6:35497
Boca, Simina M; Nishida, Maki; Harris, Michael et al. (2016) Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study. PLoS One 11:e0153461
Spikol, Emma D; Laverriere, Caroline E; Robnett, Maya et al. (2016) Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics. Diseases 4:
Cheema, Amrita K; Maier, Irene; Dowdy, Tyrone et al. (2016) Chemopreventive Metabolites Are Correlated with a Change in Intestinal Microbiota Measured in A-T Mice and Decreased Carcinogenesis. PLoS One 11:e0151190

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