The Role of Gut Microbiota in Neointimal Hyperplasia After Vascular Injury
肠道微生物群在血管损伤后新内膜增生中的作用
基本信息
- 批准号:9014333
- 负责人:
- 金额:$ 15.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-01-25 至 2020-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdvisory CommitteesAffectAmericanAngioplastyAnimal ModelAntibioticsApoptosisArterial InjuryArteriesAtherosclerosisAwardBalloon AngioplastyBasic ScienceBedsBiochemistryBiological SciencesBiologyBiophysicsBlood CirculationBlood VesselsButyratesBypassC57BL/6 MouseCardiovascular systemCell Cycle ProgressionCell ProliferationCellsChicagoChronicCicatrixCore FacilityCoronaryDataDevelopmentDevelopment PlansDiabetes MellitusDietDietary FiberDigestive System DisordersDiseaseDisease susceptibilityEndothelial CellsEnvironmentEpithelialExperimental ModelsFailureFermentationFibroblastsFoot UlcerFoundationsFundingFutureG-Protein-Coupled ReceptorsGangreneGastroenterologyGerm-FreeGoalsHealedHealth ExpendituresHospitalsHyperplasiaHypertensionImmunologyIn VitroInbreedingInfiltrationInflammationInflammatoryInflammatory Bowel DiseasesInflammatory ResponseInjuryInterventionIntestinesIsraelK-Series Research Career ProgramsKnock-outKnockout MiceKnowledgeLaboratoriesLeadLeukocytesLimb structureLinkLocationMacrophage ActivationMediatingMedicalMentorsMentorshipMicrobeModalityMolecularMorbidity - disease rateMusMyocardial InfarctionNational Institute of Diabetes and Digestive and Kidney DiseasesObesityOperative Surgical ProceduresOralPathogenesisPatientsPeripheralPhysiciansPrevalencePreventive therapyProbioticsProcessProductionPropionatesPublic HealthRattusRecurrenceResearchResearch InstituteResearch PersonnelResearch ProposalsResearch TrainingRiskRoleScientistSeasonsSerumSiteSmooth Muscle MyocytesSodium AcetateSodium ButyrateStrokeStructureSupplementationSurgeonTestingTherapeuticTimeTrainingTranslatingTreatment FailureUnited States National Institutes of HealthUniversitiesVancomycinVascular Smooth MuscleVolatile Fatty AcidsWomanWorkanimal facilitybasecareercareer developmentchemokinecohortcytokineexperiencefemoral arterygut microbiomegut microbiotahealingin vivoinnovationinsightmacrophagemeetingsmicrobialmicrobiomemicrobiotamicroorganism interactionmigrationmonocytemortalitymouse modelmultidisciplinaryneutrophilnovelnovel strategiesprebioticspreventprogramspublic health relevanceranpirnasereceptorresponseresponse to injuryrestenosisskillssoundvascular smooth muscle cell proliferation
项目摘要
DESCRIPTION (provided by applicant): Karen J. Ho's career goals are to become an independently-funded, academic vascular surgeon- scientist, advance the field of vascular surgery, and specifically reduce the burden of restenosis after interventions such as angioplasty/stenting and bypass surgery. She has a sound foundation for achieving these objectives through her undergraduate studies in molecular biophysics and biochemistry at Yale, medical training at Harvard, surgical and vascular training at Brigham and Women's Hospital, and postdoctoral research training at Brigham and Women's Hospital and Beth Israel Deaconess Hospital. Now at Northwestern University, her role is to develop a basic science research program in vascular surgery, and she has unconditional support from her Department and mentors. She also has the drive and intellect to develop a research direction in the microbiome that is new to her but which is exciting, innovative, and novel. Dr. Ho's immediate goal is to use the protected research time and mentorship structure of the K08 Award to enhance her knowledge and scientific research skills in the gut microbiome to effectively study the mechanism by which gut microbes and microbe-derived metabolites regulate neointimal hyperplasia, with the eventual goal of developing complementary or alternative dietary strategies that modulate the microbiome to reduce the risk of restenosis after arterial interventions. Atherosclerosis will continue to be a major public health problem in the foreseeable future due to the increasing prevalence of obesity, hypertension, and diabetes. Furthermore, restenosis as a cause of failure of interventions for atherosclerosis continues to be an intractable problem despite decades of research, underscoring the importance of a novel approach. Although we have a symbiotic relationship with our gut microbiota, perturbations that alter the quantity or makeup of gut microbes have been linked to chronic inflammatory diseases including obesity, diabetes, atherosclerosis, and inflammatory bowel disease. In certain cases, this relationship may involve gut microbe- derived metabolites such as short chain fatty acids (SCFA), which are produced by microbial fermentation of dietary fiber. Dr. Ho's preliminary work over the past year and a half shows that inbred rats treated with antibiotics have exacerbated neointimal hyperplasia after carotid angioplasty, an effect that is reversed by concomitant supplementation with sodium butyrate, a major SCFA. Furthermore, butyrate has an anti- proliferative and anti-migratory effect in vascular smooth muscle cells in vitro. Thus, we hypothesize that gut microbiota influence the arterial injury response through the production of SCFA. To investigate this hypothesis, the aims of this proposal are (1) to evaluate the functional role of the gut microbiome in a murine model of neointimal hyperplasia, (2) to determine if microbiome-derived SCFA regulate neointimal hyperplasia through modulation of systemic and/or local inflammation, and (3) to determine if microbiome-derived SCFA regulate neointimal hyperplasia through direct modulation of cellular proliferation, migration, and/or apoptosis. The scientific environment at Northwestern University and the University of Chicago, the mentorship team and multidisciplinary Advisory Committee, and the proposed Career Development Plan are centered around Dr. Ho's objective to use protected time to enrich her working knowledge of characterizing and manipulating the microbiome and applying these to the pathogenesis of neointimal hyperplasia. Northwestern University's Feinberg Cardiovascular Research Institute is Dr. Ho's principal location for this proposal. Dr. Melina Kibbe is Dr. Ho's primary mentor and an experienced physician-scientist in the Department of Surgery at Northwestern University. Dr. Kibbe's laboratory has expertise in animal models of neointimal hyperplasia and atherosclerosis and in vascular biology. Dr. Ho's lab in Feinberg Cardiovascular Research Institute is located in close proximity to Dr. Kibbe's and she has access to multiple Northwestern University core facilities, an animal facility, and advisors in scientific research. The University of Chicago's Biological Sciences Division Section of Gastroenterology is a second site for this proposal. Dr. Eugene B. Chang, Dr. Ho's co-mentor, is a seasoned investigator at the University of Chicago in the gut microbiome and host-microbial interactions. His research specializes in intestinal epithelial, biology/pathobiology, cultivation-dependent and cultivation-independent approaches to studying gut microbiota, and mucosal immunology. His lab in the state-of-the-art Knapp Center for Biomedical Discovery includes the NIDDK P30 Digestive Diseases Research Core Center and is only 20 minutes away by car from the Northwestern University Chicago campus. During the award period, Dr. Ho will elect formal coursework at both sites. This proposal and the assembled environmental and mentoring support plan address dual purposes: to advance Dr. Ho's scientific skills through a structured mentorship and protected scientific framework and to determine the mechanistic role of the gut microbiome in neointimal hyperplasia. The unwavering support of both Northwestern University and University of Chicago to Dr. Ho to meet these objectives will provide her with the skills necessary to achieve her goal of becoming an independent surgeon scientist.
描述(由申请人提供):Karen J. Ho的职业目标是成为一名独立资助的学术性血管外科医生-科学家,推进血管外科领域的发展,特别是减少血管成形术/支架植入术和旁路手术等干预后再狭窄的负担。她通过在耶鲁大学的分子生物物理学和生物化学本科学习、在哈佛的医学培训、在布里格姆妇女医院的外科和血管培训以及在布里格姆妇女医院和贝斯以色列女执事医院的博士后研究培训,为实现这些目标奠定了坚实的基础。现在在西北大学,她的角色是开发血管外科的基础科学研究计划,她得到了她的部门和导师的无条件支持。她也有动力和智慧来开发微生物组的研究方向,这对她来说是新的,但这是令人兴奋的,创新的,新颖的。何博士的近期目标是利用K 08奖受保护的研究时间和导师结构,提高她在肠道微生物组方面的知识和科研技能,以有效研究肠道微生物和微生物衍生代谢物调节新生内膜增生的机制,其最终目标是开发调节微生物组的补充或替代饮食策略,以降低术后再狭窄的风险。动脉介入在可预见的未来,由于肥胖、高血压和糖尿病的日益流行,动脉粥样硬化将继续成为主要的公共卫生问题。此外,尽管经过几十年的研究,再狭窄作为动脉粥样硬化干预失败的原因仍然是一个棘手的问题,强调了新方法的重要性。虽然我们与肠道微生物群有共生关系,但改变肠道微生物数量或组成的扰动与慢性炎症性疾病有关,包括肥胖症,糖尿病,动脉粥样硬化和炎症性肠病。在某些情况下,这种关系可能涉及肠道微生物衍生的代谢物,如短链脂肪酸(SCFA),其由膳食纤维的微生物发酵产生。何博士在过去一年半的初步研究表明,用抗生素治疗的近交系大鼠在颈动脉血管成形术后加剧了新生内膜增生,这种作用可以通过同时补充丁酸钠(一种主要的SCFA)来逆转。此外,丁酸盐在体外血管平滑肌细胞中具有抗增殖和抗迁移作用。因此,我们假设肠道微生物群通过SCFA的产生影响动脉损伤反应。为了研究这一假设,该提议的目的是(1)评估肠道微生物组在新生内膜增生的鼠模型中的功能作用,(2)确定微生物组来源的SCFA是否通过调节全身和/或局部炎症来调节新生内膜增生,以及(3)确定微生物组来源的SCFA是否通过直接调节细胞增殖、迁移、和/或凋亡。西北大学和芝加哥大学的科学环境、导师团队和多学科咨询委员会以及拟议的职业发展计划都围绕着何博士的目标,即利用受保护的时间来丰富她在表征和操纵微生物组方面的工作知识,并将其应用于新生内膜增生的发病机制。西北大学的Feinberg心血管研究所是何博士这项建议的主要地点。Melina Kibbe博士是何博士的主要导师,也是西北大学外科系经验丰富的内科医生兼科学家。Kibbe博士的实验室在新生内膜增生和动脉粥样硬化的动物模型以及血管生物学方面具有专业知识。何博士在Feinberg心血管研究所的实验室靠近Kibbe博士的实验室,她可以使用西北大学的多个核心设施,一个动物设施和科学研究顾问。芝加哥大学的生物科学部胃肠科是该提案的第二个网站。尤金博士B。何博士的共同导师Chang是芝加哥大学在肠道微生物组和宿主-微生物相互作用方面经验丰富的研究人员。他的研究专长是肠上皮,生物学/病理学,培养依赖和培养独立的方法来研究肠道微生物群和粘膜免疫学。他的实验室位于最先进的克纳普生物医学发现中心,包括NIDDK P30消化系统疾病研究核心中心,距离西北大学芝加哥校区仅20分钟车程。在奖励期间,何博士将在两个地点选择正式的课程。该提案和组装的环境和指导支持计划解决了双重目的:通过结构化的指导和受保护的科学框架来提高何博士的科学技能,并确定肠道微生物组在新生内膜增生中的机制作用。西北大学和芝加哥大学坚定不移地支持何博士实现这些目标,将为她提供必要的技能,以实现她成为一名独立的外科医生科学家的目标。
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 }}
KAREN J. HO其他文献
KAREN J. HO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('KAREN J. HO', 18)}}的其他基金
COCOA PAD II: Effect of Cocoa Flavanols on the Gut Microbiome and Functional Performance
COCOA PAD II:可可黄烷醇对肠道微生物组和功能表现的影响
- 批准号:
10811104 - 财政年份:2023
- 资助金额:
$ 15.93万 - 项目类别:
Targeting the Meta-organismal Butyrate Pathway to Prevent Arterial Restenosis after Vascular Surgery
靶向元生物体丁酸途径预防血管手术后动脉再狭窄
- 批准号:
10591598 - 财政年份:2021
- 资助金额:
$ 15.93万 - 项目类别:
Targeting the Meta-organismal Butyrate Pathway to Prevent Arterial Restenosis after Vascular Surgery
靶向元生物体丁酸途径预防血管手术后动脉再狭窄
- 批准号:
10374926 - 财政年份:2021
- 资助金额:
$ 15.93万 - 项目类别:
Targeting the Meta-organismal Butyrate Pathway to Prevent Arterial Restenosis after Vascular Surgery
靶向元生物体丁酸途径预防血管手术后动脉再狭窄
- 批准号:
10210817 - 财政年份:2021
- 资助金额:
$ 15.93万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 15.93万 - 项目类别:
Research Grant