Diversity Supplement Support for a Graduate Student Training in the Studies of HDAC11
为 HDAC11 研究研究生培训提供多样性补充支持
基本信息
- 批准号:10380445
- 负责人:
- 金额:$ 8.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AcylationAdipose tissueAdultAffectAttenuatedBody fatBrown FatCancer BiologyCancer ModelCell LineCell ProliferationCellular Metabolic ProcessChronic DiseaseCyclic AMPCyclic AMP-Dependent Protein KinasesDeacetylationDiglyceridesDiseaseDrug resistanceEventFunctional disorderHDAC11 geneHealthcareHigh Fat DietHomeostasisImmuneInfiltrationInterferonsKnowledgeLeadLiverLymphomaLysineMalignant NeoplasmsMediatingMetabolicMetabolismMissionModelingModificationMusNeoplasm MetastasisNon-Insulin-Dependent Diabetes MellitusObesityObesity associated cancerOrganOverweightPathway interactionsPlasmaPlayRegulationRiskRoleSignal TransductionTestingThermogenesisTissuesTriglyceridesTumor ImmunityUnited States National Institutes of HealthWorkWorld Health Organizationacyl groupadiponectincell motilitydiacylglycerol O-acyltransferasedisabilityexperimental studyfatty acylationgraduate studentimprovedinhibitor/antagonistlipid metabolismnon-alcoholic fatty liver diseasenovelnovel strategiesnovel therapeuticsobesity developmentobesity treatmentparent grantstudent trainingtreatment strategy
项目摘要
Project Summary
Cell metabolism plays a central role in cancer biology including cell proliferation, invasion/metastasis, and
drug resistance. In addition to cancer, dysregulated cellular metabolism has been shown to be associated with
obesity and the development of many chronic illnesses. According to the World Health Organization >2.1
billion adults are estimated to be overweight or obese globally, and accumulating, consistent, evidence
suggests that higher amounts of body fat are associated with increased risks of a number of cancers.
Previously, we discovered an essential role of histone deacetylase 11 (HDAC11) in metabolism
homeostasis. More recently, our studies revealed a novel enzymatic activity of HDAC11, removing long-chain
fatty acyl groups, that is >10,000-fold higher than the presumed deacetylation activity. Further, our recent
preliminary studies show: 1) HDAC11 KO promotes the expression of UCP1 and boosts the thermogenic
capacity of brown adipose tissue; 2) Lack of HDAC11 elevates the level of plasma adiponectin, a key
messenger involved in communicating between adipose tissue and other organs, and suppresses metabolic
derangements, leading to type 2 diabetes, obesity, and non- alcoholic fatty liver disease; 3) HDAC11
deficiency not only results in the accumulation of diacylglycerol (DG) and metabolites, but also attenuates the
triacylglycerol (TAG) level in the liver, indicating dysfunction of diglyceride acyltransferase 2 (DGAT2).
In this diversity supplement application, the Supplement Candidate will rigorously test the hypothesis that
the novel defatty-acylation activity of HDAC11 is critical for its impact on HFD-driven metabolic reprogramming.
The Candidate will focus on elucidating major HDAC11 KO-driven events in key lipid metabolism tissues by
performing the following studies: 1) investigate the role of HDAC11 as a regulator of thermogenesis through
the UCP1 pathway in BAT and examine whether HDAC11 altered Cdc42-fatty-acylation plays a crucial role in
cAMP/PKA mediated UCP1 expression; 2) examine the effect of HDAC11 on adiponectin function in white
adipose tissue and investigate the impact of HDAC11 on adiponectin conserved lysine-modification and
multimerization; 3) explore HDAC11 KO-induced suppression of TAG synthesis through affecting DGAT
function in liver tissue and investigate the role of BASP1 in DGAT regulation.
The proposed experiments in this supplement are distinct from, yet highly relevant to, the proposed work in
the parent grant. The supplemental project will contribute to, expands and extends, our understandings of
HDAC11 in cancer. Ultimately, it may lead to new approaches for the treatment of obesity-related cancer
diseases.
项目摘要
细胞代谢在癌症生物学中起着核心作用,包括细胞增殖、侵袭/转移和转移。
耐药性除了癌症,细胞代谢失调已被证明与癌症有关。
肥胖和许多慢性疾病的发展。世界卫生组织(WHO)2.1
据估计,全球有10亿成年人超重或肥胖,
研究表明,体内脂肪含量较高与多种癌症的风险增加有关。
以前,我们发现组蛋白去乙酰化酶11(HDAC 11)在代谢中的重要作用
体内平衡最近,我们的研究揭示了HDAC 11的一种新的酶活性,
脂肪酰基,即比假定的脱乙酰化活性高> 10,000倍。此外,我们最近
初步研究表明:1)HDAC 11 KO可促进UCP 1的表达,增强产热细胞的增殖,
2)HDAC 11的缺乏提高了血浆脂联素的水平,这是一个关键因素。
信使参与脂肪组织和其他器官之间的沟通,并抑制代谢
紊乱,导致2型糖尿病、肥胖和非酒精性脂肪肝; 3)HDAC 11
缺乏不仅导致二酰基甘油(DG)和代谢产物的积累,而且还减弱了
肝脏中的甘油三酯(TAG)水平,指示甘油二酯酰基转移酶2(DGAT 2)的功能障碍。
在这个多样性补充申请中,补充候选人将严格测试假设,
HDAC 11的新的去脂肪酰化活性对于其对HFD驱动的代谢重编程的影响是关键的。
候选人将通过以下方式重点阐明关键脂质代谢组织中的主要HDAC 11 KO驱动事件:
进行以下研究:1)研究HDAC 11作为产热调节剂的作用,
BAT中UCP 1通路,并检查HDAC 11是否改变Cdc 42-脂肪酰化在
cAMP/PKA介导的UCP 1表达; 2)检测HDAC 11对白色小鼠脂联素功能的影响。
研究HDAC 11对脂联素保守赖氨酸修饰的影响,
3)探索HDAC 11 KO通过影响DGAT诱导的TAG合成抑制
在肝组织中的功能,并研究BASP 1在DGAT调节中的作用。
在本补充建议的实验是不同的,但高度相关,拟议的工作,
家长补助金补充项目将有助于,扩大和扩展,我们的理解,
HDAC 11与癌症最终,它可能会导致治疗肥胖相关癌症的新方法
疾病
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 }}
Rong Li其他文献
Rong Li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('Rong Li', 18)}}的其他基金
Boosting Antitumor Immunity by Blocking Both Tumor and Adipose DDR1
通过阻断肿瘤和脂肪 DDR1 来增强抗肿瘤免疫力
- 批准号:
9980667 - 财政年份:2020
- 资助金额:
$ 8.18万 - 项目类别:
Supplement to Support Research Training in HDAC11 and Cancer
支持 HDAC11 和癌症研究培训的补充品
- 批准号:
10380397 - 财政年份:2020
- 资助金额:
$ 8.18万 - 项目类别:
Boosting Antitumor Immunity by Blocking Both Tumor and Adipose DDR1
通过阻断肿瘤和脂肪 DDR1 来增强抗肿瘤免疫力
- 批准号:
10395597 - 财政年份:2020
- 资助金额:
$ 8.18万 - 项目类别:
相似海外基金
Deciphering the role of adipose tissue in common metabolic disease via adipose tissue proteomics
通过脂肪组织蛋白质组学解读脂肪组织在常见代谢疾病中的作用
- 批准号:
MR/Y013891/1 - 财政年份:2024
- 资助金额:
$ 8.18万 - 项目类别:
Research Grant
ESTABLISHING THE ROLE OF ADIPOSE TISSUE INFLAMMATION IN THE REGULATION OF MUSCLE MASS IN OLDER PEOPLE
确定脂肪组织炎症在老年人肌肉质量调节中的作用
- 批准号:
BB/Y006542/1 - 财政年份:2024
- 资助金额:
$ 8.18万 - 项目类别:
Research Grant
Canadian Alliance of Healthy Hearts and Minds: Dissecting the Pathways Linking Ectopic Adipose Tissue to Cognitive Dysfunction
加拿大健康心灵联盟:剖析异位脂肪组织与认知功能障碍之间的联系途径
- 批准号:
479570 - 财政年份:2023
- 资助金额:
$ 8.18万 - 项目类别:
Operating Grants
Determinants of Longitudinal Progression of Adipose Tissue Inflammation in Individuals at High-Risk for Type 2 Diabetes: Novel Insights from Metabolomic Profiling
2 型糖尿病高危个体脂肪组织炎症纵向进展的决定因素:代谢组学分析的新见解
- 批准号:
488898 - 财政年份:2023
- 资助金额:
$ 8.18万 - 项目类别:
Operating Grants
Activation of human brown adipose tissue using food ingredients that enhance the bioavailability of nitric oxide
使用增强一氧化氮生物利用度的食品成分激活人体棕色脂肪组织
- 批准号:
23H03323 - 财政年份:2023
- 资助金额:
$ 8.18万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of new lung regeneration therapies by elucidating the lung regeneration mechanism of adipose tissue-derived stem cells
通过阐明脂肪组织干细胞的肺再生机制开发新的肺再生疗法
- 批准号:
23K08293 - 财政年份:2023
- 资助金额:
$ 8.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A study on the role of brown adipose tissue in the development and maintenance of skeletal muscles
棕色脂肪组织在骨骼肌发育和维持中作用的研究
- 批准号:
23K19922 - 财政年份:2023
- 资助金额:
$ 8.18万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Adipose Tissue T Cell Polarization and Metabolic Health in Persons Living with HIV
HIV 感染者的脂肪组织 T 细胞极化和代谢健康
- 批准号:
10619176 - 财政年份:2023
- 资助金额:
$ 8.18万 - 项目类别:
Estrogen Signaling in the Ventromedial Hypothalamus Modulates Adipose Tissue Metabolic Adaptation
下丘脑腹内侧区的雌激素信号调节脂肪组织代谢适应
- 批准号:
10604611 - 财政年份:2023
- 资助金额:
$ 8.18万 - 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
- 批准号:
10813753 - 财政年份:2023
- 资助金额:
$ 8.18万 - 项目类别: