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program leaders---nuclear receptor

项目负责人---核受体

基本信息

批准号：
8181351
负责人：
ORLA M. CONNEELY
金额：
$ 1.49万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-17 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8181351
关键词：
Acute Myelocytic Leukemia Adopted Basic Science Biochemical Biological Biological Models Breast Breast Cancer Cell Cancer Center Cancer Model Cells Chromatin Clinic Clinical Code Collaborations Complex Department of Defense Development Disclosure Employment Epithelial Evaluation Foundations Funding Gene Expression Gene Silencing Gene Targeting Generations Genes Genetic Heterogeneity Goals Homeostasis Human Institutes Intervention Knock-out Malignant Neoplasms Malignant neoplasm of prostate Manuscripts Mediating Medicine Modeling Molecular Molecular Analysis Molecular Mechanisms of Action Molecular Profiling Mus Neoplasm Metastasis Nuclear Orphan Receptor Nuclear Receptor Subfamily 4, Group A, Member 1 Nuclear Receptors Oncogenes Orphan Patients Pattern Peer Review Preclinical Drug Evaluation Predisposition Prevention Preventive Prognostic Marker Proteins Publications Publishing Regulation Research Research Support Role Scientist Signal Pathway Steroids Therapeutic Therapeutic Intervention Tissues Transcriptional Regulation Transgenic Organisms Translations Tumor Suppressor Proteins United States National Institutes of Health angiogenesis apoAI regulatory protein-1 carcinogenesis cell growth regulation college meetings member mouse model new therapeutic target novel nuclear receptor coactivator 1 overexpression pre-clinical programs promoter receptor reproductive steroid hormone receptor transcription factor tumor tumorigenesis

项目摘要

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.

核受体项目是一个由20位美国国立卫生研究院资助的基础科学家组成的网络