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 #
3P30CA046934-25S2
Application #
8710564
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
25
Fiscal Year
2013
Total Cost
$963
Indirect Cost
$340
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Finlay-Schultz, J; Cittelly, D M; Hendricks, P et al. (2015) Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a. Oncogene 34:3676-87
Alvarez-Calderon, Francesca; Gregory, Mark A; Pham-Danis, Catherine et al. (2015) Tyrosine kinase inhibition in leukemia induces an altered metabolic state sensitive to mitochondrial perturbations. Clin Cancer Res 21:1360-72
Roth, Lauren W; Bradshaw-Pierce, Erica L; Allshouse, Amanda A et al. (2014) Evidence of GnRH antagonist escape in obese women. J Clin Endocrinol Metab 99:E871-5
Kumar, Sushil; Raina, Komal; Agarwal, Chapla et al. (2014) Silibinin strongly inhibits the growth kinetics of colon cancer stem cell-enriched spheroids by modulating interleukin 4/6-mediated survival signals. Oncotarget 5:4972-89
Roth, Lauren W; Allshouse, Amanda A; Bradshaw-Pierce, Erica L et al. (2014) Luteal phase dynamics of follicle-stimulating and luteinizing hormones in obese and normal weight women. Clin Endocrinol (Oxf) 81:418-25
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Colussi, Timothy M; Costantino, David A; Hammond, John A et al. (2014) The structural basis of transfer RNA mimicry and conformational plasticity by a viral RNA. Nature 511:366-9
Griesinger, Andrea M; Donson, Andrew M; Foreman, Nicholas K (2014) Immunotherapeutic implications of the immunophenotype of pediatric brain tumors. Oncoimmunology 3:e27256
Teodorovic, Lenka S; Babolin, Chiara; Rowland, Sarah L et al. (2014) Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies. Proc Natl Acad Sci U S A 111:E2797-806
Holliday, Michael J; Zhang, Fengli; Isern, Nancy G et al. (2014) 1H, 13C, and 15N backbone and side chain resonance assignments of thermophilic Geobacillus kaustophilus cyclophilin-A. Biomol NMR Assign 8:23-7

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