The Cancer Genetics and Epigenetics (CGE) Program was formed in 2012 and consists of 52 members (36 primary, 15 associate and 1 adjunct) from 10 departments. Dr. Sharon Dent, an international leader in defining the function and regulation of histone-modifying proteins, leads the program. Dr. Guillermina Lozano, a leading authority on the p53 tumor suppressor pathway, and Dr. David Johnson, an expert on the functions of the E2F family of proteins in transcription, DNA repair and cell growth control, serve as co-leaders. The major scientific goal of the program is to define the genetic, epigenetic and mechanistic changes that influence cancer to develop new and effective means to positively impact cancer diagnosis, treatment and cure. The program is organized around 3 major themes: 1) Oncogenes and Tumor Suppressors, 2) Epigenetic Regulators, and 3) Genome Maintenance. Each theme is addressed by a specific aim.
Aim 1 : To define molecular pathways important in human cancers using genetic and genomic approaches in model organisms, cellular systems and patient-derived tissues;
Aim 2 : To define functions of epigenetic regulators in normal and disease states and explore how these functions can be exploited for development of new therapeutics or diagnostics;
Aim 3 : To define the molecular machinery that responds to DNA damage and other stresses to maintain genome integrity and tissue homeostasis and to understand how dysfunction of these mechanisms contributes to cancer. CGE annual direct funding totals $10.2M with $2.5M from the NCI, $7.7M from other peer-reviewed sources, such as CPRIT, the Leukemia & Lymphoma Society, the American Cancer Society, and breast and prostate cancer research funding from the U.S. Department of Defense. Total program peer-reviewed funding reflects an increase of 7% since the last competitive renewal. The program has also produced 779 published papers, with 132 (17%) reflecting intra- programmatic collaborations (an increase of 5%), 270 (35%) reflecting inter-programmatic collaborations (an increase of 6%), and 571 (73%) reflecting inter-institutional collaborations. Sixty-five percent of articles appeared in journals with IF >5, and 27% of articles were published in journals with IF >10, including N Engl J Med, Nature, Science, Lancet Oncol, Cell, Cancer Cell, Cancer Discov, J Clin Oncol, and JAMA Oncol. Program members have collectively used all CCSG shared resources. Research accomplishments during the last grant period include definition of the origin and evolution of breast tumor cell heterogeneity, development of the first small- molecule inhibitor of the TRIM24 bromodomain, identification of the YEATS domain as a new epigenetic ?reader? of acetylated lysine implicated in leukemia and non-small cell lung cancer, and the discovery that the BRCA1- interacting protein ABRAXAS and the related protein ABRO1, maintain genome integrity. These and other discoveries reflect the impact of our contributions to defining the mutations, epigenetic alterations, and cellular mechanisms that underlie oncogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA016672-44
Application #
9997813
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
44
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
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Zinn, Pascal O; Singh, Sanjay K; Kotrotsou, Aikaterini et al. (2018) A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models. Clin Cancer Res 24:6288-6299
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Childress, Merrida A; Himmelberg, Stephen M; Chen, Huiqin et al. (2018) ALK Fusion Partners Impact Response to ALK Inhibition: Differential Effects on Sensitivity, Cellular Phenotypes, and Biochemical Properties. Mol Cancer Res 16:1724-1736
Zhang, Wei; Liu, Bo; Wu, Wenhui et al. (2018) Targeting the MYCN-PARP-DNA Damage Response Pathway in Neuroendocrine Prostate Cancer. Clin Cancer Res 24:696-707
Vijayaraghavan, Smruthi; Moulder, Stacy; Keyomarsi, Khandan et al. (2018) Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions. Target Oncol 13:21-38

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