The Nuclear Receptor Program is a network of 20 NIH funded basic scientists focused on understanding the contribution of nuclear receptor transcription factor and chromatic modifying coregulator function to cancer development. Members have a total of $14,612,144 in peer-reviewed research support, $4,167,979 of which is from NCI and the remainder from other NIH institutes, the Department of Defense, and cancer foundation funds. Members of the Program have a strong record of both intraprogramatic collaboration and interprogramatic interactions with both basic and clinical programs throughout the cancer center. During the last three years, members published 202 peer reviewed manuscripts of which 39% were the result of intraprogrammatic interactions and 34% from interrogrammatic publications. A major goal to identify novel therapeutic targets among members of the nuclear receptor superfamily and nuclear receptor interacting coregulator proteins for prevention of and therapeutic intervention in cancer. To achieve this goal, we have adopted an integrative approach with three central components: 1) nuclear receptor and coregulator discovery and analysis of their mechanisms of regulation of cellular homeostasis, 2) preclinical assessment of their roles in cancer development using genetically manipulated mouse model systems, and 3) A translational component involving interaction with clinical programs to rapidly transfer new information into receptor profiling and assessment of therapeutic potential in human cancers. Major accomplishments include elucidation of a breast cancer cell selective posttranslational code that is responsible for overexpression of the pi60 coactivator I breast cancer cells, SRC-3 in breast cancer cells;identification of a critical role of coactivators SRC-1 and SRC-3 in breast and prostate cancer metastases;discovery of the orphan nuclear receptors, NR4A1 and NR4A3 as novel tumor suppressors of acute myeloid leukemia and discovery of their widespread gene silencing in human AML patients regardless of genetic heterogeneity;and discovery of the orphan COUP-TFII as a potent driver of epithelial tumor associated angiogenesis and metastasis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA125123-08
Application #
8690562
Study Section
Subcommittee B - Comprehensiveness (NCI)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77030
Woodard, Lauren E; Cheng, Jizhong; Welch, Richard C et al. (2017) Kidney-specific transposon-mediated gene transfer in vivo. Sci Rep 7:44904
Saxena, Kapil; Simon, Lukas M; Zeng, Xi-Lei et al. (2017) A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection. Proc Natl Acad Sci U S A 114:E570-E579
Heczey, Andras; Louis, Chrystal U; Savoldo, Barbara et al. (2017) CAR T Cells Administered in Combination with Lymphodepletion and PD-1 Inhibition to Patients with Neuroblastoma. Mol Ther 25:2214-2224
Rohira, Aarti D; Yan, Fei; Wang, Lei et al. (2017) Targeting SRC Coactivators Blocks the Tumor-Initiating Capacity of Cancer Stem-like Cells. Cancer Res 77:4293-4304
Ware, Matthew J; Nguyen, Lam P; Law, Justin J et al. (2017) A new mild hyperthermia device to treat vascular involvement in cancer surgery. Sci Rep 7:11299
Gibbons, Don L; Creighton, Chad J (2017) Pan-cancer survey of epithelial-mesenchymal transition markers across the Cancer Genome Atlas. Dev Dyn :
Ha, Kyungsoo; Ma, Chengxian; Lin, Han et al. (2017) The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites. Nat Commun 8:15751
Schmueck-Henneresse, Michael; Omer, Bilal; Shum, Thomas et al. (2017) Comprehensive Approach for Identifying the T Cell Subset Origin of CD3 and CD28 Antibody-Activated Chimeric Antigen Receptor-Modified T Cells. J Immunol 199:348-362
Wang, Yongquan; Wang, Jianghua; Zhang, Li et al. (2017) RGS12 Is a Novel Tumor-Suppressor Gene in African American Prostate Cancer That Represses AKT and MNX1 Expression. Cancer Res 77:4247-4257
Sreekumar, Amulya; Toneff, Michael J; Toh, Eajer et al. (2017) WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis. Dev Cell 43:436-448.e6

Showing the most recent 10 out of 842 publications