Nuclear Receptor, Transcription and Chromatin Biology Program
核受体、转录和染色质生物学项目
基本信息
- 批准号:10674560
- 负责人:
- 金额:$ 3.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcute Myelocytic LeukemiaAddressAgonistAndrogen ReceptorAreaBasic ScienceBiologyCancer CenterCancer Center Support GrantCancer ModelCancer Prevention InterventionChromatinClinicClinicalClinical Trials DesignClinical assessmentsCollaborationsCytoskeletonDefectDependenceDevelopmentDirect CostsDisclosureDiseaseDysmyelopoietic SyndromesEpigenetic ProcessEstrogen ReceptorsEvaluationFundingGeneticGenetic TranscriptionGlucocorticoid ReceptorGoalsGrantHumanHuman GeneticsInternationalLinkMalignant NeoplasmsMalignant neoplasm of liverMalignant neoplasm of prostateMalignant neoplasm of urinary bladderMediatingMedicineMetastatic Prostate CancerMicroRNAsMolecular GeneticsMolecular TargetMolecular and Cellular BiologyMutationNamesNuclear ReceptorsOncogenicPathogenesisPeer ReviewPharmaceutical PreparationsPharmacologyPreclinical TestingPrognostic MarkerPublicationsRUNX1 geneRegulationResearchResearch PersonnelResistanceRoleScientific Advances and AccomplishmentsSertralineSignal TransductionTamoxifenTherapeuticTherapeutic InterventionTrainingTranscriptional RegulationTranslational ResearchTranslationsUnited States National Institutes of HealthValidationapoAI regulatory protein-1cancer cellcancer clinical trialcarcinogenesiscollegeepigenetic regulationexperiencehormone therapyinsightinter-institutionalinvestigator-initiated trialmalignant breast neoplasmmembermennew therapeutic targetnovelnovel therapeuticspatient derived xenograft modelpre-clinicalpreventive interventionprogramsprostate cancer metastasisracial disparitysmall moleculetargeted treatmenttreatment responsetumorigenesis
项目摘要
NUCLEAR RECEPTOR, TRANSCRIPTION, AND CHROMATIN BIOLOGY (NRTBC) PROGRAM
PROJECT SUMMARY
The overall objective of the NRTCB program is to conduct impactful basic research and to promote rapid
translation of discoveries linked to NR-dependent and epigenetic mechanisms of transcriptional regulation of
carcinogenesis to the clinic to accelerate development of new preventative and therapeutic interventions. The
program has 2 main themes: (1) Identification of NRs that contribute to cancer pathogenesis and progression,
disclosure of their mechanisms of action, and evaluation of their potential as novel therapeutic targets, and (2)
Biology and function of chromatin regulators that mediate epigenetic regulation of transcription in cancer. The
program has 20 actively funded Research Members, 2 Clinical, 2 Adjunct, and one Shared Member with
extensive research experience related to the 2 themes and drawn from several departments including Medicine,
Molecular and Cellular Biology, Molecular and Human Genetics, and Pharmacology. The program is led by Dr.
Suzanne Fuqua, a translational research expert in estrogen receptor action in breast cancer, together with 2 Co-
Leaders, Dr. Cheryl Walker, an internationally recognized expert on environmental, genetic, and epigenetic factor
interactions in cancer and Dr. Nicholas Mitsiades, a clinical researcher with extensive experience in oncology
clinical trial design and execution in the area of NRs and prostate cancer. Members of the Program have $15.9
million (direct costs) in cancer-related research funding, of which $9.9 million is peer-reviewed and $6 million is
non peer-reviewed. Peer-reviewed funding includes nearly $6.4 million in NIH support, of which $5.3 million is
from the NCI. NRTCB Program members have a strong record of programmatic interactions as evidenced by 16
externally funded programmatic grants. Members continue to make outstanding research progress as evidenced
by over 321 cancer-related publications over the past 5 years of which 25% and 70% involve intra- and inter-
programmatic collaborations and 52% are inter-institutional. Major scientific accomplishments include novel
discoveries of (1) a role of androgen receptors in breast cancer resistance to endocrine therapies, (2) a role for
the NR, CAR in liver cancer, (3) a novel miRNA-regulated signaling axis required for suppression of COUP-TFII
driven prostate cancer metastasis, (4) glucocorticoid receptors as novel therapeutic targets for RUNX1-ETO
positive acute myeloid leukemia, (5) a role for epigenetic regulators in control of cytoskeletal dynamics, (6) a role
for Warburg-associated glycolytic reprogramming in epigenetic activation of SRC-3 driven oncogenic
transcriptional programs, and (7) a role for prostate cancer associated mutations in SPOP in regulation of
androgen receptor turnover. Translational advances include: (1) Preclinical validation of the NR4A activator,
dihydroergotamine, as a novel therapeutic drug for AML, (2) Four new investigator-initiated trials including:
tamoxifen for treatment of bladder cancer; meclizine, an inverse agonist for CAR, for treatment of liver cancer;
Sertraline for treatment of myelodysplastic syndrome; and racial disparities in hormonal therapy response in men
with metastatic prostate cancer, and (3) Commercial development of new first-in-class therapies targeting SRC-
3 with Coactigon Inc.
核受体、转录和染色质生物学 (NRTBC) 计划
项目概要
NRTCB 计划的总体目标是开展有影响力的基础研究并促进快速发展
与 NR 依赖性和表观遗传转录调控机制相关的发现的翻译
将致癌作用推向临床,以加速开发新的预防和治疗干预措施。这
计划有 2 个主题:(1) 鉴定有助于癌症发病机制和进展的 NR,
披露其作用机制,并评估其作为新治疗靶点的潜力,以及(2)
介导癌症转录表观遗传调控的染色质调节因子的生物学和功能。这
该计划有 20 名积极资助的研究成员、2 名临床成员、2 名兼职成员和 1 名共享成员
与这两个主题相关的丰富研究经验来自多个部门,包括医学、
分子和细胞生物学、分子和人类遗传学以及药理学。该计划由博士领导。
Suzanne Fuqua,一位乳腺癌雌激素受体作用的转化研究专家,与 2 位同事一起
领导者:Cheryl Walker 博士,国际公认的环境、遗传和表观遗传因素专家
癌症和拥有丰富肿瘤学经验的临床研究员 Nicholas Mitsiades 博士之间的相互作用
NR 和前列腺癌领域的临床试验设计和执行。该计划的会员有 15.9 美元
百万(直接费用)的癌症相关研究经费,其中 990 万美元用于同行评审,600 万美元用于
未经同行评审。同行评审资金包括近 640 万美元的 NIH 支持,其中 530 万美元是
来自国家癌症研究所。 NRTCB 计划成员拥有良好的计划互动记录,16 个国家就证明了这一点
外部资助的方案赠款。事实证明,成员继续取得杰出的研究进展
过去 5 年发表了超过 321 篇癌症相关出版物,其中 25% 和 70% 涉及癌症内部和外部
计划合作,52% 是机构间合作。主要科学成就包括新颖
发现 (1) 雄激素受体在乳腺癌对内分泌治疗耐药性中的作用,(2)
肝癌中的 NR、CAR,(3) 抑制 COUP-TFII 所需的新型 miRNA 调节信号轴
驱动前列腺癌转移,(4)糖皮质激素受体作为RUNX1-ETO的新治疗靶点
阳性急性髓系白血病,(5) 表观遗传调节因子在控制细胞骨架动力学中的作用,(6)
用于 SRC-3 驱动致癌的表观遗传激活中 Warburg 相关糖酵解重编程
转录程序,以及(7)前列腺癌相关 SPOP 突变在调节中的作用
雄激素受体周转。转化进展包括:(1) NR4A 激活剂的临床前验证,
二氢麦角胺作为 AML 的新型治疗药物,(2) 四项新的研究者发起的试验,包括:
他莫昔芬用于治疗膀胱癌; meclizine,一种 CAR 反向激动剂,用于治疗肝癌;
舍曲林用于治疗骨髓增生异常综合征;男性激素治疗反应的种族差异
转移性前列腺癌,以及(3)针对 SRC- 的新型一流疗法的商业开发
3 与 Coactigon Inc.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Suzanne AW Fuqua其他文献
Suzanne AW Fuqua的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Suzanne AW Fuqua', 18)}}的其他基金
Translational Breast Cancer Research Training Program
转化乳腺癌研究培训计划
- 批准号:
10475088 - 财政年份:2018
- 资助金额:
$ 3.26万 - 项目类别:
Translational Breast Cancer Research Training Program
转化乳腺癌研究培训计划
- 批准号:
10249135 - 财政年份:2018
- 资助金额:
$ 3.26万 - 项目类别:
MECHANISMS OF AR-ER COLLABORATION IN HORMONE RESISTANCE AND METASTASIS OF BREAST CANCER
AR-ER 在乳腺癌激素抵抗和转移中的合作机制
- 批准号:
9884532 - 财政年份:2017
- 资助金额:
$ 3.26万 - 项目类别:
MECHANISMS OF AR-ER COLLABORATION IN HORMONE RESISTANCE AND METASTASIS OF BREAST CANCER
AR-ER 在乳腺癌激素抵抗和转移中的合作机制
- 批准号:
9316124 - 财政年份:2017
- 资助金额:
$ 3.26万 - 项目类别:
MECHANISMS OF AR-ER COLLABORATION IN HORMONE RESISTANCE AND METASTASIS OF BREAST CANCER
AR-ER 在乳腺癌激素抵抗和转移中的合作机制
- 批准号:
10113551 - 财政年份:2017
- 资助金额:
$ 3.26万 - 项目类别:
Nuclear Receptor, Transcription and Chromatin Biology Program
核受体、转录和染色质生物学项目
- 批准号:
10439821 - 财政年份:2007
- 资助金额:
$ 3.26万 - 项目类别:
Cancer Research Career Enhancement and Related Activities
癌症研究职业提升及相关活动
- 批准号:
10239116 - 财政年份:2007
- 资助金额:
$ 3.26万 - 项目类别:
相似海外基金
Computing analysis of leukemic stem cell dynamics in acute myelocytic leukemia
急性粒细胞白血病白血病干细胞动力学的计算分析
- 批准号:
19K08356 - 财政年份:2019
- 资助金额:
$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Generation of immunotoxins with super-targeting mAb in the acute myelocytic leukemia
在急性髓细胞白血病中使用超靶向单克隆抗体产生免疫毒素
- 批准号:
23501309 - 财政年份:2011
- 资助金额:
$ 3.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
DETERMINANTS OF RESPONSE OF ACUTE MYELOCYTIC LEUKEMIA
急性粒细胞白血病反应的决定因素
- 批准号:
3556971 - 财政年份:1980
- 资助金额:
$ 3.26万 - 项目类别:
DETERMINANTS OF RESPONSE OF ACUTE MYELOCYTIC LEUKEMIA
急性粒细胞白血病反应的决定因素
- 批准号:
3556968 - 财政年份:1980
- 资助金额:
$ 3.26万 - 项目类别:
ERADICATION OF ACUTE MYELOCYTIC LEUKEMIA CELLS BY MAB THERAPY
通过 MAB 疗法根除急性粒细胞白血病细胞
- 批准号:
3889304 - 财政年份:
- 资助金额:
$ 3.26万 - 项目类别:














{{item.name}}会员




