The Molecular Oncology (MO) Program studies fundamental molecular processes such as DNA damage and repair, gene expression control and protein/RNA structure. Members collaborate with other programs to translate these basic discoveries into better tools for cancer diagnostics, prevention and therapy. Novel technologies and approaches to address these areas developed by the program include synthetic lethal shRNA screens in human cells to identify pathways conferring resistance to targeted therapies, new phospho-proteomics approaches to elucidate oncogenic protein kinase signaling pathways, and advanced crystallographic and NMR studies of protein structure. The Program has three integrated focus groups: 1) Maintenance of Genomic Integrity; 2) Gene Expression and Biomarkers; 3) Structural Biology. In the past five years MO members have made major discoveries including: 1) Development of a new combinatorial therapy for CML currently entering clinical trials; 2) Elucidation of the structure of various epigenetic regulators (JMJD2, INGS, p53BP1) as well as the Nterminal domain of telomerase; 3) Elucidation of the mechanism of action of the CDK8 oncoprotein; 4) Development of an inexpensive HPV vaccine to be used in developing countries; 5) Identification of novel targets of the oncogenic protein kinase B-RAF; 6) Elucidation of mechanisms of transcriptional control by the tumor suppressor p53; and 7) Identification of novel cancer biomarkers for lung, thyroid and breast cancer. MO has 44 full members in 16 departments in 5 schools at the University of Colorado Denver and Boulder campuses, Colorado State University (CSU) and National Jewish Health. Members currently hold $2.9M in NCI-funded research grants and $16.8M in other cancer-relevant research support. Per capita cancer research funding has increased by 39% from $324K in 2005, to $449K in 2010. MO produced 561 cancerrelated publications between 2005 and 2010. Of these, 130 (23%) were inter-programmatic; 43 (8%) were intra-programmatic; and 13 (2%) were both inter- and intra-programmatic. Thus, 183 (33%) of the total cancer-related publications by members of this program were collaborative.

Public Health Relevance

The Molecular Oncology Program (MO) organizes a productive group of researchers whose work provides insights into gene expression regulation and its deregulation in cancer, the cellular response to genomic insults, the molecular structure of cancer-relevant proteins, and new signaling transduction processes driving tumor growth. With the UCCC they translate their basic discoveries into better tools for cancer prevention, diagnosis and treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
4P30CA046934-28
Application #
9001259
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2016-02-01
Budget End
2017-01-31
Support Year
28
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
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Vartuli, Rebecca L; Zhou, Hengbo; Zhang, Lingdi et al. (2018) Eya3 promotes breast tumor-associated immune suppression via threonine phosphatase-mediated PD-L1 upregulation. J Clin Invest 128:2535-2550
Scott, Aaron J; Arcaroli, John J; Bagby, Stacey M et al. (2018) Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms. Mol Cancer Ther 17:2112-2122
da Silva, Raquel Frenedoso; Dhar, Deepanshi; Raina, Komal et al. (2018) Nintedanib inhibits growth of human prostate carcinoma cells by modulating both cell cycle and angiogenesis regulators. Sci Rep 8:9540
Majtan, Tomas; Jones Jr, Wendell; Krijt, Jakub et al. (2018) Enzyme Replacement Therapy Ameliorates Multiple Symptoms of Murine Homocystinuria. Mol Ther 26:834-844
Dhar, Deepanshi; Deep, Gagan; Kumar, Sushil et al. (2018) Bitter melon juice exerts its efficacy against pancreatic cancer via targeting both bulk and cancer stem cells. Mol Carcinog 57:1166-1180
Donson, Andrew M; Amani, Vladimir; Warner, Elliot A et al. (2018) Identification of FDA-Approved Oncology Drugs with Selective Potency in High-Risk Childhood Ependymoma. Mol Cancer Ther 17:1984-1994
Branchford, B R; Stalker, T J; Law, L et al. (2018) The small-molecule MERTK inhibitor UNC2025 decreases platelet activation and prevents thrombosis. J Thromb Haemost 16:352-363
Pei, Shanshan; Minhajuddin, Mohammad; Adane, Biniam et al. (2018) AMPK/FIS1-Mediated Mitophagy Is Required for Self-Renewal of Human AML Stem Cells. Cell Stem Cell 23:86-100.e6
Ren, Shengxiang; Rivard, Christopher J; Yu, Hui et al. (2018) A miRNA Panel Predicts Sensitivity of FGFR Inhibitor in Lung Cancer Cell Lines. Clin Lung Cancer 19:450-456

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