Defining and Controlling Airway Disease
定义和控制气道疾病
基本信息
- 批准号:10352375
- 负责人:
- 金额:$ 94.5万
- 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:2019-03-08 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressAirway DiseaseAsthmaAttenuatedBackCause of DeathCell Differentiation processCell ProliferationCell SeparationCell physiologyCellsCellular biologyChargeChromatinChronic Obstructive Pulmonary DiseaseDataDiseaseDrug DesignEnvironmentEpithelial CellsExtramural ActivitiesFunctional disorderGenomicsGoalsHomeostasisHumanImmuneImmune responseIndividualInfectionInterruptionLeadLinkLungMedical ResearchMentorsMissionMitoticMolecularMolecular TargetMorbidity - disease rateMucous body substanceNational Heart, Lung, and Blood InstitutePathogenesisPathway interactionsPhosphotransferasesPopulationPrevention therapyProductionProteomicsPublic HealthResearchResearch PersonnelResourcesRoleScientistStructureTechnologyTherapeutic InterventionTissuesTrainingTransplantationUniversitiesValidationViralWorkairway epitheliumairway repairbasecareer developmentcell behaviorcellular targetingchronic respiratory diseaseeffective therapyepithelial stem cellinnovationlung developmentmortalitymouse modelmultidisciplinarynovel strategiesporcine modelprogramsrespiratory virusresponse to injurystem cellstranslational impactwater channel
项目摘要
Abstract
Airway epithelial cells were originally regarded as an inert barrier to the environment, but are now viewed as key
regulators of the response to injury and infection with a critical role in airway repair that mimics lung development.
Furthermore, altered behavior of this cell population is central to the pathogenesis of common airway diseases
such as asthma and COPD, making it essential to understand the mechanisms responsible to normal and
abnormal programming of this cell population. My research program is thematically focused on airway epithelial
cell programming with the goal of characterizing the molecular basis of airway epithelial cell function and
dysfunction for airway homeostasis versus disease. Our work to date has contributed to new paradigms in airway
epithelial cell biology, including the first evidence of an active role for airway epithelial cells in directing the
immune response towards airway disease and now the first data for an elusive airway progenitor epithelial cell
(APEC) population that can be respiratory-virus activated to orchestrate disease and thereby explain how a
transient infection could lead to long-term disease. Building on this work, we will focus going forward on creating
a new concept for tissue homeostasis versus disease based on a set of transformative paradigms where
progenitor cell reprogramming switches a normal airway epithelial barrier to one dominated by mucus production
and the consequent morbidity and mortality of airway disease. We will provide the first definition of the key
population of airway progenitor epithelial cells and the first mechanisms for how these cells are switched to
disease-producing cells, incorporating unprecedented roles for: (1) endogenous viral, water channel, and
nucleokine control of mitotic chromatin in these cells; and (2) an exogenous danger loop from these cells to
immune cells and back to drive a distinct progenitor-cell kinase now targeted with structure-based drug design
to interrupt mucus production. Translational impact also derives from new mouse and pig models and validation
in humans with comparable disease. This substrate is combined with new approaches to cell isolation, 3D
manipulation, and transplantation based on targets identified from genomic and proteomic analyses. Each of the
individual approaches within the overall Program is charged to investigators in training to integrate scientific
career development into the mission for medical research and discovery. In addition, the Program relies on vital
and sophisticated input from senior pulmonary scientists for additional mentoring and cutting-edge approaches
and innovations. The Program also incorporates the wider University and extramural resources to deploy
multidisciplinary technologies with outstanding collaborators. Together, we expect our Program to provide a
transformative paradigm for true progenitor epithelial cell programming and its role in cell proliferation and
differentiation, including skewing towards mucous cell formation and excess mucus production that is central to
airway disease. We also fully expect that our studies will identify the first tractable cellular and molecular targets
and corresponding therapeutic intervention to attenuate airway disease, consistent with the mission of NHLBI.
摘要
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(1)
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 }}
Michael J Holtzman其他文献
Distinct characteristics of T cell rolling and adhesion in splenic versus lymph node vessels
- DOI:
10.1016/s0091-6749(02)82116-9 - 发表时间:
2002-01-01 - 期刊:
- 影响因子:
- 作者:
Mitchell H Grayson;Michael J Holtzman;David D Chaplin - 通讯作者:
David D Chaplin
Michael J Holtzman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('Michael J Holtzman', 18)}}的其他基金
INTERFERON SIGNAL ENHANCERS AS ANTIVIRAL THERAPEUTICS
干扰素信号增强剂作为抗病毒治疗
- 批准号:
8697863 - 财政年份:2014
- 资助金额:
$ 94.5万 - 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:
$ 94.5万 - 项目类别:
Fellowship
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:
$ 94.5万 - 项目类别:
Continuing Grant
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:
$ 94.5万 - 项目类别:
Research 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:
$ 94.5万 - 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:
$ 94.5万 - 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:
$ 94.5万 - 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:
$ 94.5万 - 项目类别:
EU-Funded
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:
$ 94.5万 - 项目类别:
Standard Grant
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:
$ 94.5万 - 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:
$ 94.5万 - 项目类别:
Research Grant