Fibrosis of the Lower Esophageal Sphincter in Achalasia
贲门失弛缓症下食管括约肌纤维化
基本信息
- 批准号:10592076
- 负责人:
- 金额:$ 15.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-15 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AchalasiaApoptosisAtropineBiologicalBiologyBiomechanicsBiometryCaliforniaCell CommunicationCell Culture TechniquesCell DegranulationChymaseClinical InvestigatorClinical ResearchClinical TrialsCoculture TechniquesCollagenDataData AnalysesDeformityDeglutitionDevelopmentDigestive System DisordersDilatation - actionDiseaseElementsEnteralEsophageal DiseasesEsophageal motility disordersEsophagusExtracellular MatrixFibroblastsFibronectinsFibrosisFunctional disorderFundingFutureGangliaGoalsGrantIgE ReceptorsImpairmentIn VitroInferior esophageal sphincter structureLaboratoriesLeadLearningMachine LearningMaster of ScienceMeasurementMeasuresMechanicsMediatingMedicineMentorsMentorshipMolecularMolecular BiologyMuscleMuscle functionMyenteric PlexusMyopathyNatural HistoryNerve DegenerationNeuronsNitric Oxide DonorsPathogenesisPatient-Focused OutcomesPatientsPharmacologyPhysiologicalPhysiologyPlayPropertyProto-Oncogene Protein c-kitRecurrenceRelaxationResearch PersonnelResearch TrainingResourcesRoleScientistSecondary toSmooth MuscleSmooth Muscle Actin Staining MethodSmooth Muscle MyocytesSphincterStainsTechniquesTestingTimeTissuesTrainingTrichrome stain methodTryptaseUniversitiesVariantWorkcareercareer developmentcytokineexperimental studyfunctional disabilityimaging probeimprovedin vivoinhibitory neuronmast cellmedical schoolsmolecular targeted therapiesneuromechanismnew technologynovelrelating to nervous systemresponsetranslational scientist
项目摘要
Project Summary / Abstract
Achalasia is an esophageal motility disorder characterized by impaired lower esophageal sphincter opening
with swallowing. Achalasia is thought to be caused by ganglion loss in the neural plexus that innervates the
lower esophageal sphincter muscle. Despite excellent approaches to open the lower esophageal sphincter in
achalasia, disease recurrence in achalasia is common. As such, it may be there are additional biomechanical
elements that cause sphincter dysfunction in achalasia. In particular the fibrosis of the lower esophageal
sphincter muscle may play a critical role. This proposal will study the molecular mechanism and physiological
impact of muscle fibrosis in achalasia. Recently, it has been identified that mast cell activation and
degranulation is a prominent feature in achalasia. In this proposal, we will assess the impact of muscle fibrosis
on physiological function of the LES (Aim 1). We will use a novel technology, functional lumen imaging probe
(FLIP) topography, to conduct in vivo experiments and perform ex vivo muscle strip recordings. In Aim 2, we
will assess the mechanism of mast cell activation in causing fibrosis via fibrosis marker expression and cell
culture experiments. This study will facilitate an understanding of the alternative mechanisms of disease
pathogenesis and functional impairment in achalasia. Ultimately this may lead to novel treatment approaches
in achalasia such as molecularly targeted therapy. This study will also provide an in-depth understanding of the
precise components measured by the functional lumen imaging probe. In order to accomplish the aims put
forth in this grant and his career goal as becoming an independent clinical and translational investigator in the
field of esophageal motility disorders, the Principle Investigator, Dr. Anand Jain, will require in-depth training in
both fundamental and advanced biological laboratory techniques used to study smooth muscle, esophageal
functional data analysis, and biostatistics. His career development is enthusiastically supported by his strong
mentorship team, led by R01-funded enteric neuronal biologist Dr. Shanthi Srinivasan at Emory and including
R01-funded esophageal translational esophageal physiologist Dr. Ravinder Mittal from University of California
San Diego. The robust training resources available via the Emory University School of Medicine and protected
time and in kind support provided by the Emory University Department of Medicine and the Division of
Digestive Diseases will facilitate his transformation to an independent clinician scientist.
项目概要/摘要
贲门失弛缓症是一种食管运动障碍,其特征是下食管括约肌开口受损
随着吞咽。贲门失弛缓症被认为是由神经丛神经节缺失引起的,该神经丛支配着
下食管括约肌。尽管有很好的方法来打开食管下括约肌
贲门失弛缓症,贲门失弛缓症疾病复发很常见。因此,可能还有额外的生物力学
导致贲门失弛缓症括约肌功能障碍的因素。特别是食管下段纤维化
括约肌可能发挥关键作用。该提案将研究分子机制和生理学
肌肉纤维化对贲门失弛缓症的影响。最近,已经发现肥大细胞的激活和
脱粒是贲门失弛缓症的一个显着特征。在本提案中,我们将评估肌肉纤维化的影响
LES 的生理功能(目标 1)。我们将使用一种新技术,功能性管腔成像探头
(FLIP)地形,进行体内实验并进行离体肌肉条记录。在目标 2 中,我们
将通过纤维化标志物表达和细胞评估肥大细胞激活引起纤维化的机制
培养实验。这项研究将有助于了解疾病的替代机制
失弛缓症的发病机制和功能障碍。最终这可能会带来新的治疗方法
贲门失弛缓症,例如分子靶向治疗。这项研究还将深入了解
由功能性管腔成像探头测量的精确成分。为了实现所提出的目标
在这笔资助中,他的职业目标是成为一名独立的临床和转化研究者
在食管动力障碍领域,首席研究员 Anand Jain 博士将需要接受深入的培训
用于研究平滑肌、食管的基础和先进生物实验室技术
功能数据分析和生物统计学。他的职业发展得到了他强大的支持
导师团队由 R01 资助的埃默里大学肠神经生物学家 Shanthi Srinivasan 博士领导,成员包括
R01资助的食管平移食管生理学家来自加州大学的Ravinder Mittal博士
圣地亚哥。埃默里大学医学院提供强大的培训资源并受到保护
埃默里大学医学系和医学部提供的时间和实物支持
消化系统疾病将促进他向独立临床科学家的转变。
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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Anand Sagar Jain其他文献
Anand Sagar Jain的其他文献
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{{ truncateString('Anand Sagar Jain', 18)}}的其他基金
Fibrosis of the Lower Esophageal Sphincter in Achalasia
贲门失弛缓症下食管括约肌纤维化
- 批准号:
10705229 - 财政年份:2022
- 资助金额:
$ 15.05万 - 项目类别:
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