Diversity Supplement for PhD student Shamarie King under Multi-Scale Investigations of Respiratory Mucus/Mucin Structure and Function in Health and Disease
博士生 Shamarie King 在健康和疾病中呼吸道粘液/粘蛋白结构和功能的多尺度研究中的多样性补充
基本信息
- 批准号:10852415
- 负责人:
- 金额:$ 10.26万
- 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:2022-08-15 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAirAsthmaBindingBiochemicalBiochemistryBiologicalBiologyBiophysicsBiostatistics CoreBronchiectasisCactaceaeCharacteristicsChronicChronic Obstructive Pulmonary DiseaseChronic lung diseaseCiliaCiliary Motility DisordersClawCommunicable DiseasesComplementCystic FibrosisDNADevelopmentDiseaseDistalDoctor of PhilosophyElectronsElectrostaticsElementsEnsureFailureFunctional disorderGelGenesGenetic studyGeometryGlandGoalsHealthHost DefenseHumanHydration statusHydrophobicityImageIn VitroInfectious AgentInhalationInvestigationKnowledgeLeftLengthLungLung diseasesMeasurementMembraneMicroscopicMolecularMolecular BiologyMorphologyMucinsMucolyticsMucous body substanceMusNatureObstructionOutcomePathogenesisPatientsPolymersPopulationPower strokePredispositionPropertyPublic HealthPumpQuality ControlReagentRecording of previous eventsRegulationResearchResearch PersonnelRespiratory DiseaseRespiratory MucinRiskRoleSeriesSkinSlideStretchingStructureSubmucosaSurfaceSystemTandem Repeat SequencesTestingTherapeuticTherapeutic AgentsToxic Environmental SubstancesToxinWaterWorkairway surface liquidaqueousbiophysical propertiescombatcrosslinkdimerdoctoral studenteffective therapyfluid flowgenetic approachimprovedin vivolung healthmucus clearancemucus-associated lung diseasesneutrophilnovelnovel therapeuticsrare genetic disorderrespiratorytherapy developmenttransmission processtreatment strategyviscoelasticity
项目摘要
OVERALL ABSTRACT
The mucus clearance system constitutes the primary airway host defense system against inhaled infectious
agents and toxins. However, despite more than two centuries of research into the nature of the mucus clearance
system, surprising gaps in our knowledge of fundamental aspects of this system persist. Filling in these gaps is
important for improving public health strategies to combat respiratory infectious diseases. Filling in these gaps
is also important for elucidating the pathogenesis of and developing therapies for chronic pulmonary diseases,
including COPD, asthma, NCFB, and rare genetic diseases (CF, PCD), which are by definition characterized by
mucus accumulation in the lung. This PPG proposes to investigate fundamental, but poorly understood, aspects
of the mucus clearance system that must be quantitated to understand mucus function in health and dysfunction
in disease. Each PPG project has two specific aims focused on basic mucin function and one focused on
translational aspects of mucin pathobiology. Project 1 (“Mucin Structure and Associations in Respiratory Mucus”,
Michael Rubinstein, PhD, PI) will investigate fundamental aspects of the organization of mucins in solution and
within the mucus layer. These studies will be complemented by studies of the addition of “abnormal polymers”,
e.g., DNA, to mucus solutions. Project 2 (“Why are mucins so gigantic and is it safe/effective to sever them
therapeutically?”, Richard C. Boucher, MD, PI) will focus on the fundamental question as to why human airway
mucin polymers are of such enormous size (300 MDa, Rg 250 nm) and characterize the ratio of efficacy (chain
length reduction) vs risk (off-target chain unwinding) required for the development of mucolytics for lung disease.
Project 3 (“Membrane-bound mucins on the airway surface ensure efficient mucus clearance and lung health”,
Brian Button, PhD, PI) will study the relationships between cilia, PCL, and the mucus layer required for transport,
focusing on a novel hydraulic “pushing” vs classic “clawing” mechanisms. In addition, barrier functions of PCL
and regulation thereof will be studied. Project 4 (“Biophysical and structural characterization of airway
submucosal gland mucus in health and cystic fibrosis”, Ronit Freeman, PhD, PI) will focus on a novel attribute
of submucosal gland (SMG) mucus, a strand/bundle insoluble component, and how strands/bundles contribute
to SMG mucus function in health and disease. Three cores support the PPG: 1) Core A, the
Administrative/Biostatistical Core, Multi-PIs Richard C. Boucher, MD, and Michael Rubinstein, PhD, supplies
project management and statistical support for the PPG; 2) Core B, the Mucus/Mucin Analytics Core, PI Mehmet
Kesimer, PhD, provides quality control of all mucin reagents for the PPG and novel biochemical/biophysical
measurements; and 3) Core C, the Imaging Core, PI Camille Ehre, PhD, provides electron microscopic,
molecular, and morphologic analyses to the projects. The overall goals of the PPG are to elucidate the structure
and function of mucus in health, how these characteristics are degraded in disease, and identify strategies for
development of novel therapeutic agents to treat muco-obstructive diseases.
整体的抽象
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nanocolloidal hydrogel mimics the structure and nonlinear mechanical properties of biological fibrous networks.
- DOI:10.1073/pnas.2220755120
- 发表时间:2023-12
- 期刊:
- 影响因子:11.1
- 作者:Elisabeth Prince;S. Morozova;Zhengkun Chen;Vahid Adibnia;I. Yakavets;Sergey Vladimir Panyukov;M. Rubinst
- 通讯作者:Elisabeth Prince;S. Morozova;Zhengkun Chen;Vahid Adibnia;I. Yakavets;Sergey Vladimir Panyukov;M. Rubinst
Entropic Mixing of Ring/Linear Polymer Blends.
环/线性聚合物混合物的熵混合。
- DOI:10.1021/acspolymersau.2c00050
- 发表时间:2023-04-12
- 期刊:
- 影响因子:0
- 作者:Grest GS;Ge T;Plimpton SJ;Rubinstein M;O'Connor TC
- 通讯作者:O'Connor TC
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Richard Charles Boucher其他文献
Richard Charles Boucher的其他文献
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{{ truncateString('Richard Charles Boucher', 18)}}的其他基金
UNC Research Training Program in Respiratory Diseases and Critical Care
北卡罗来纳大学呼吸系统疾病和重症监护研究培训计划
- 批准号:
10714527 - 财政年份:2023
- 资助金额:
$ 10.26万 - 项目类别:
The molecular and cellular mechanisms of the STAT3 mutation-mediated pulmonary disorder in Autosomal Dominant Hyper IgE Syndrome (AD-HIES)
常染色体显性高 IgE 综合征 (AD-HIES) STAT3 突变介导的肺部疾病的分子和细胞机制
- 批准号:
10393987 - 财政年份:2022
- 资助金额:
$ 10.26万 - 项目类别:
Project 2: Why are mucins so gigantic and is it safe/effective to sever them therapeutically?
项目 2:为什么粘蛋白如此巨大?在治疗上切断它们是否安全/有效?
- 批准号:
10684198 - 财政年份:2022
- 资助金额:
$ 10.26万 - 项目类别:
The molecular and cellular mechanisms of the STAT3 mutation-mediated pulmonary disorder in Autosomal Dominant Hyper IgE Syndrome (AD-HIES)
常染色体显性高 IgE 综合征 (AD-HIES) STAT3 突变介导的肺部疾病的分子和细胞机制
- 批准号:
10584596 - 财政年份:2022
- 资助金额:
$ 10.26万 - 项目类别:
Multi-Scale Investigations of Respiratory Mucus/Mucin Structure and Function in Health and Disease
健康和疾病中呼吸道粘液/粘蛋白结构和功能的多尺度研究
- 批准号:
10684185 - 财政年份:2022
- 资助金额:
$ 10.26万 - 项目类别:
Mucin sialylation drives epithelial cell senescence and severe asthma
粘蛋白唾液酸化导致上皮细胞衰老和严重哮喘
- 批准号:
10206266 - 财政年份:2020
- 资助金额:
$ 10.26万 - 项目类别:
Mucin sialylation drives epithelial cell senescence and severe asthma
粘蛋白唾液酸化导致上皮细胞衰老和严重哮喘
- 批准号:
10664889 - 财政年份:2020
- 资助金额:
$ 10.26万 - 项目类别:
Mucin sialylation drives epithelial cell senescence and severe asthma
粘蛋白唾液酸化导致上皮细胞衰老和严重哮喘
- 批准号:
10026633 - 财政年份:2020
- 资助金额:
$ 10.26万 - 项目类别:
Mucin sialylation drives epithelial cell senescence and severe asthma
粘蛋白唾液酸化导致上皮细胞衰老和严重哮喘
- 批准号:
10434719 - 财政年份:2020
- 资助金额:
$ 10.26万 - 项目类别:
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湍流和化学交互作用对H2-Air-H2O微混燃烧中NO生成的影响研究
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