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
Collins, Keagan P; Jackson, Kristen M; Gustafson, Daniel L (2018) Hydroxychloroquine: A Physiologically-Based Pharmacokinetic Model in the Context of Cancer-Related Autophagy Modulation. J Pharmacol Exp Ther 365:447-459
Villalobos, Victor Manuel; Hall, Francis; Jimeno, Antonio et al. (2018) Long-Term Follow-Up of Desmoid Fibromatosis Treated with PF-03084014, an Oral Gamma Secretase Inhibitor. Ann Surg Oncol 25:768-775
Montford, John R; Lehman, Allison M B; Bauer, Colin D et al. (2018) Bone marrow-derived cPLA2? contributes to renal fibrosis progression. J Lipid Res 59:380-390
Kogut, Igor; McCarthy, Sandra M; Pavlova, Maryna et al. (2018) High-efficiency RNA-based reprogramming of human primary fibroblasts. Nat Commun 9:745
Goodspeed, Andrew; Jean, Annie; Costello, James C (2018) A Whole-genome CRISPR Screen Identifies a Role of MSH2 in Cisplatin-mediated Cell Death in Muscle-invasive Bladder Cancer. Eur Urol :
Niemeyer, Brian F; Oko, Lauren M; Medina, Eva M et al. (2018) Host Tumor Suppressor p18INK4c Functions as a Potent Cell-Intrinsic Inhibitor of Murine Gammaherpesvirus 68 Reactivation and Pathogenesis. J Virol 92:
Kiseljak-Vassiliades, Katja; Zhang, Yu; Bagby, Stacey M et al. (2018) Development of new preclinical models to advance adrenocortical carcinoma research. Endocr Relat Cancer 25:437-451
Nellan, Anandani; Rota, Christopher; Majzner, Robbie et al. (2018) Durable regression of Medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. J Immunother Cancer 6:30
Abraham, Christopher G; Ludwig, Michael P; Andrysik, Zdenek et al. (2018) ?Np63? Suppresses TGFB2 Expression and RHOA Activity to Drive Cell Proliferation in Squamous Cell Carcinomas. Cell Rep 24:3224-3236
Sanchez, Gilson J; Richmond, Phillip A; Bunker, Eric N et al. (2018) Genome-wide dose-dependent inhibition of histone deacetylases studies reveal their roles in enhancer remodeling and suppression of oncogenic super-enhancers. Nucleic Acids Res 46:1756-1776

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