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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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Baylor College of Medicine
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Addison, Joseph B; Koontz, Colton; Fugett, James H et al. (2015) KAP1 promotes proliferation and metastatic progression of breast cancer cells. Cancer Res 75:344-55
Torbit, Lindsey A; Albiani, Jenna J; Crangle, Cassandra J et al. (2015) Fear of recurrence: the importance of self-efficacy and satisfaction with care in gay men with prostate cancer. Psychooncology 24:691-8
Ramasamy, Ranjith; Ridgeway, Alex; Lipshultz, Larry I et al. (2014) Integrative DNA methylation and gene expression analysis identifies discoidin domain receptor 1 association with idiopathic nonobstructive azoospermia. Fertil Steril 102:968-973.e3
Kowalkowski, Marc A; Day, Rena S; Du, Xianglin L et al. (2014) Cumulative HIV viremia and non-AIDS-defining malignancies among a sample of HIV-infected male veterans. J Acquir Immune Defic Syndr 67:204-11
Thrift, Aaron P; Garcia, Jose M; El-Serag, Hashem B (2014) A multibiomarker risk score helps predict risk for Barrett's esophagus. Clin Gastroenterol Hepatol 12:1267-71
Bhattacharya, Abhisek; Parillon, Xyanthine; Zeng, Shenyan et al. (2014) Deficiency of autophagy in dendritic cells protects against experimental autoimmune encephalomyelitis. J Biol Chem 289:26525-32
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Geldres, Claudia; Savoldo, Barbara; Hoyos, Valentina et al. (2014) T lymphocytes redirected against the chondroitin sulfate proteoglycan-4 control the growth of multiple solid tumors both in vitro and in vivo. Clin Cancer Res 20:962-71
Young, Evelin; Zheng, Ze-Yi; Wilkins, Angela D et al. (2014) Regulation of Ras localization and cell transformation by evolutionarily conserved palmitoyltransferases. Mol Cell Biol 34:374-85
Anurathapan, Usanarat; Leen, Ann M; Brenner, Malcolm K et al. (2014) Engineered T cells for cancer treatment. Cytotherapy 16:713-33

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