The Markey Cancer Center's Cancer Cell Biology and Signaling (CS) Research Program includes a robust array of thematically driven projects performed by a cohesive and highly collaborative group of investigators. The overarching goal is to better understand cancer signaling networks in order to identify novel targets that can be exploited to create new therapeutic combinations. To achieve this objective, the CS program is divided into 3 thematic areas: 1) Aberrant proliferation and survival networks, 2) Determinants of tumor progression and metastasis, and 3) Interaction of tumor cells with their microenvironment. Inter-related subthemes within each goal reflect the scope of the research projects and individual expertise across the cross-cutting topic of ?Cell Signaling.? These include regulation of oncogene/tumor suppressor and kinase/phosphatase gene networks (Theme 1); contribution of cell motility/ epithelial-mesenchymal transition and cancer stem cells to therapeutic resistance (Theme 2); and examination of cellular and matrix contributions to cancer development and progression (Theme 3). Members of the CS program are experts in defining cancer signaling pathways that underlie the mechanisms of cancer cell survival, proliferation, invasion, and metastasis, and deciphering the relationship between the tumor and the micro- and macro-environments that modulate the dynamics of tumor progression. CS members include leaders in the field of survival/apoptosis signaling in response to growth factors/cytokines, adhesion, and anoikis, as well as experts in the processes of epithelial-mesenchymal transition, cell motility, and invasion. The 26 members of the program represent 3 colleges at the University of Kentucky and 9 different departments, reflecting diverse disciplinary perspectives that provided significant new insights into CS program thematic areas. The CS program has a total annual external cancer-related funding of $7.4M ($5.1M annual direct costs, of which $2.4M (48%) is from the National Cancer Institute). Members published 231 publications between 2013 and 2017, of which 90 (39%) are inter-programmatic, 55 (24%) are intra-programmatic, and 134 (58%) are inter-institutional. Led by CS program Co-leaders, Drs. Vivek Rangnekar (an expert in studying cell survival and apoptosis) and Rina Plattner (an expert in tumor invasion and metastasis), CS research focuses on reducing the most serious cancer burdens in Kentucky by identifying novel therapeutic targets in signaling pathways that drive cancer development and progression. In collaboration with other program leaders and Associate Directors for Basic Research and Clinical Translation, research of the CS program has led to 2 new clinical trials and eight new patents. Additionally, working with the Associate Director for Cancer Education and Mentoring, the Co-leaders of the CS program have instituted a robust mentoring system to ensure the success of junior faculty. By bringing a wide array of expertise and programmatic strengths, the CS program collectively provides a rich environment to facilitate multidisciplinary collaboration and builds a productive pipeline for translation of CS science into the clinic.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA177558-08
Application #
9962318
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
8
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40526
Liu, Jinpeng; Murali, Thilakam; Yu, Tianxin et al. (2018) Characterization of Squamous Cell Lung Cancers from Appalachian Kentucky. Cancer Epidemiol Biomarkers Prev :
Ore, Robert M; Chen, Quan; DeSimone, Christopher P et al. (2018) Population-Based Analysis of Patient Age and Other Disparities in the Treatment of Ovarian Cancer in Central Appalachia and Kentucky. South Med J 111:333-341
Hubbard, W Brad; Harwood, Christopher L; Geisler, John G et al. (2018) Mitochondrial uncoupling prodrug improves tissue sparing, cognitive outcome, and mitochondrial bioenergetics after traumatic brain injury in male mice. J Neurosci Res 96:1677-1688
Alghamedy, Fatemah; Bopaiah, Jeevith; Jones, Derek et al. (2018) Incorporating Protein Dynamics Through Ensemble Docking in Machine Learning Models to Predict Drug Binding. AMIA Jt Summits Transl Sci Proc 2017:26-34
Wen, Yang-An; Xiong, Xiaopeng; Zaytseva, Yekaterina Y et al. (2018) Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer. Cell Death Dis 9:265
Zhang, Hui; Fredericks, Tricia; Xiong, Gaofeng et al. (2018) Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance. Breast Cancer Res 20:116
Zhong, Weixiong; Weiss, Heidi L; Jayswal, Rani D et al. (2018) Extracellular redox state shift: A novel approach to target prostate cancer invasion. Free Radic Biol Med 117:99-109
Xiong, Gaofeng; Stewart, Rachel L; Chen, Jie et al. (2018) Collagen prolyl 4-hydroxylase 1 is essential for HIF-1? stabilization and TNBC chemoresistance. Nat Commun 9:4456
Liu, Xinan; Yu, Ye; Liu, Jinpeng et al. (2018) A novel data structure to support ultra-fast taxonomic classification of metagenomic sequences with k-mer signatures. Bioinformatics 34:171-178
Al-Darraji, Ahmed; Haydar, Dalia; Chelvarajan, Lakshman et al. (2018) Azithromycin therapy reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction: Potential therapeutic targets in ischemic heart disease. PLoS One 13:e0200474

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