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 #
5P30CA046934-26
Application #
8616641
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
26
Fiscal Year
2014
Total Cost
$63,875
Indirect Cost
$23,197
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Harder, Bryan; Tian, Wang; La Clair, James J et al. (2017) Brusatol overcomes chemoresistance through inhibition of protein translation. Mol Carcinog 56:1493-1500
Chen, Yufei; Anastassiadis, Konstantinos; Kranz, Andrea et al. (2017) MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia. Cancer Cell 31:755-770.e6
DeRyckere, Deborah; Lee-Sherick, Alisa B; Huey, Madeline G et al. (2017) UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models. Clin Cancer Res 23:1481-1492
Scarborough, Hannah A; Helfrich, Barbara A; Casás-Selves, Matias et al. (2017) AZ1366: An Inhibitor of Tankyrase and the Canonical Wnt Pathway that Limits the Persistence of Non-Small Cell Lung Cancer Cells Following EGFR Inhibition. Clin Cancer Res 23:1531-1541
Neelakantan, Deepika; Zhou, Hengbo; Oliphant, Michael U J et al. (2017) EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun 8:15773
Barón, Anna E; Kako, Severine; Feser, William J et al. (2017) Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer. J Thorac Oncol 12:1512-1523
Todd, Maria C; Langan, Thomas A; Sclafani, Robert A (2017) Doxycycline-Regulated p16MTS1 Expression Suppresses the Anchorage-Independence and Tumorigenicity of Breast Cancer Cell Lines that Lack Endogenous p16. J Cancer 8:190-198
Brown, Dustin G; Borresen, Erica C; Brown, Regina J et al. (2017) Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial. Br J Nutr 117:1244-1256
Haverkos, Bradley M; Abbott, Diana; Hamadani, Mehdi et al. (2017) PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood 130:221-228
Shearn, Colin T; Saba, Laura M; Roede, James R et al. (2017) Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH. Free Radic Biol Med 113:280-290

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