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.
项目总结
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)
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Rong Li其他文献
Rong Li的其他文献
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{{ 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:
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