Microbial-derived factors regulating mucosal wound healing
调节粘膜伤口愈合的微生物衍生因子
基本信息
- 批准号:10093031
- 负责人:
- 金额:$ 5.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-02-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:Abdominal PainAcademic skillsActinsBacterial TranslocationBasic ScienceBiochemicalBiomedical ResearchBody Weight decreasedButyratesCaringCell Culture TechniquesCell ShapeCellsChronicClinicalColitisColonic DiseasesDiarrheaDiseaseEnergy-Generating ResourcesEnvironmentEnvironmental Risk FactorEpithelialEpithelial CellsEquilibriumEtiologyFermentationFosteringGastrointestinal tract structureGeneticHealthHemorrhageHistone DeacetylaseHistone Deacetylase InhibitorHomeostasisHypoxia Inducible FactorImmune responseImmune systemImmunofluorescence ImmunologicImpaired wound healingInflammationInflammatoryInflammatory Bowel DiseasesInjuryIntestinal MucosaIntestinesLinkMaintenanceMentorshipMetabolismMicrobeModelingMolecularMorbidity - disease rateMucositisMucous MembraneMusNeuronsPathogenicityPatientsPatternPhysiciansProcessProductionProteinsQuality of lifeRecoveryRegulationRelapseReporterResearchResearch TrainingResolutionResourcesRoleScienceScientistSignal TransductionSupplementationSurfaceTestingTherapeuticTight JunctionsTissuesTrainingVolatile Fatty AcidsWorkbasecare costscareercell motilityclinical practicecolon bacteriacytokineepithelial woundexperiencegut microbiotahost microbiomeimprovedin vivoinflammatory disease of the intestineinsightintestinal barrierintestinal epitheliumknock-downlife time costloss of functionmicrobialmicrobiotamicroorganismmonolayernoveloverexpressionpodocyteprogramspromoterprotein expressionrepairedresponsesingle cell sequencingsynaptopodinsynergismtissue repairtranscription factorwound healing
项目摘要
PROJECT SUMMARY/ABSTRACT
Inflammatory bowel disease (IBD) currently afflicts more than 3.1 million people in the U.S. with over 100,000
new cases each year. Patients with IBD experience persistent and relapsing gastrointestinal tract inflammation
causing abdominal pain, bleeding, diarrhea, and weight loss. The etiology of IBD, while unknown, centers around
the loss of intestinal barrier integrity, and comprises both genetic and environmental factors, with emerging
significance of shifts in the gut microbiota. Intestinal epithelial cells (IECs) form the dynamic barrier isolating the
host immune system from the external environment. Rapid wound healing after the repeated damage and barrier
disruption seen in IBD is crucial to inflammatory resolution. An established role of the microbiota is production of
energy in the form short-chain fatty acids (SCFAs), such as butyrate. Decreases in butyrate-producing species
are strongly associated with IBD. Preliminary studies show that butyrate augments barrier formation and
enhances epithelial wound healing following injury. An unbiased single cell sequencing screen revealed that
butyrate induces IEC expression of synaptopodin (SYNPO), an actin-associated protein previously
uncharacterized in the intestinal epithelium. This proposal will test the hypothesis that the microbial-derived
SCFA butyrate promotes intestinal wound healing and barrier through coordination of SYNPO expression and
function in the context of inflammation resolution as well as homeostatic maintenance. Three specific aims will
guide this project. Aim 1 will define the mechanisms of SYNPO regulation by SCFAs, including butyrate, through
cell culture and promoter reporter analysis. Aim 2 will elucidate the functional role of SYNPO in IECs utilizing
knockdown and overexpression cells and immunofluorescence. Aim 3 will determine the contribution of SYNPO
in health and during mucosal disease using murine colitis models. Successful completion of this work will
establish a critical role for the microbiota in regulating wound healing and ultimately recovery from IBD through
a novel target, SYNPO. Understanding the mechanisms through which butyrate repairs tissue damage and
restores the intestinal barrier will contribute to current therapeutic approaches.
This comprehensive research training plan will provide outstanding mentorship with an experienced sponsor
in the ideal environment of a rigorous basic science lab that is well-integrated clinically with the necessary
resources for completing each aspect of this project. This includes a distinct mentorship team within the Mucosal
Inflammation Program in addition to the guidance of the applicant’s thesis committee. This training will foster the
applicant’s research and academic skills to pursue cross-cutting molecular level science that will advance
therapeutics for tissue damage repair and novel disease target identification. These mechanistic studies hold
translational potential to improve the quality of life for IBD patients and provide the optimal progression towards
a career balancing biomedical research and clinical practice as a physician scientist.
项目总结/文摘
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 }}
Ruth Xinhe Wang其他文献
Ruth Xinhe Wang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('Ruth Xinhe Wang', 18)}}的其他基金
Microbial-derived factors regulating mucosal wound healing
调节粘膜伤口愈合的微生物衍生因子
- 批准号:
9756103 - 财政年份:2019
- 资助金额:
$ 5.1万 - 项目类别:
Microbial-derived factors regulating mucosal wound healing
调节粘膜伤口愈合的微生物衍生因子
- 批准号:
10318115 - 财政年份:2019
- 资助金额:
$ 5.1万 - 项目类别:
相似海外基金
Development of Analysis System of Academic Skills and Learning Status for Curriculum Management
课程管理学术技能与学习状况分析系统的开发
- 批准号:
19K02703 - 财政年份:2019
- 资助金额:
$ 5.1万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Research on holistic evaluation focusing on non-academic skills in entrance examinations for higher school under the old systems.
旧体制下高考非学业技能整体评价研究
- 批准号:
19K02854 - 财政年份:2019
- 资助金额:
$ 5.1万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Academic skills and reproductive behavior among adolescent girls.
青春期女孩的学术技能和生殖行为。
- 批准号:
9224720 - 财政年份:2016
- 资助金额:
$ 5.1万 - 项目类别:
The Study of Social Processes to Acquire Academic Skills in the Transition from Pre-School to Elementary Schoolhonk
从学前班到小学过渡期间获得学术技能的社会过程研究honk
- 批准号:
16K17422 - 财政年份:2016
- 资助金额:
$ 5.1万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Development of teaching materials and methods to deepen self-awareness of basic academic skills on emphasized EQ of univercity students at first-year students
开发一年级学生强调情商的教材和方法以加深基本学术技能的自我意识
- 批准号:
15K01045 - 财政年份:2015
- 资助金额:
$ 5.1万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Preventing Drug Use: Interactive Program to Improve Academic Skills
预防吸毒:提高学术技能的互动计划
- 批准号:
7802476 - 财政年份:2010
- 资助金额:
$ 5.1万 - 项目类别:
Development of Ubiquitous Support System for Teachers and Parents to Enrich Academic Skills of Students
开发教师和家长无处不在的支持系统,以丰富学生的学术技能
- 批准号:
15300278 - 财政年份:2003
- 资助金额:
$ 5.1万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Enhancing basic academic skills of low-achieving students: the role of automaticity in numeracy, reading and comprehension
提高成绩差的学生的基本学术技能:自动性在计算、阅读和理解中的作用
- 批准号:
DP0345508 - 财政年份:2003
- 资助金额:
$ 5.1万 - 项目类别:
Discovery Projects
DISCOURSE AND ACADEMIC SKILLS IN CHILDREN WITH SPINA BIFIDA
脊柱裂儿童的言语和学术技能
- 批准号:
6564761 - 财政年份:2002
- 资助金额:
$ 5.1万 - 项目类别:
DISCOURSE AND ACADEMIC SKILLS IN CHILDREN WITH SPINA BIFIDA
脊柱裂儿童的言语和学术技能
- 批准号:
6449388 - 财政年份:2001
- 资助金额:
$ 5.1万 - 项目类别: