Uncovering the Mechanisms of PFAS-induced Immunotoxicity
揭示 PFAS 诱导免疫毒性的机制
基本信息
- 批准号:10115847
- 负责人:
- 金额:$ 9.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-28 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AcidsAdaptive Immune SystemAddressAffectAirAnimal ModelAnimalsAntibodiesAntibody FormationAntigensB-Cell DevelopmentB-LymphocytesBioenergeticsBiologicalBiological AssayBiomedical ResearchCause of DeathCell LineCell physiologyCellsChemical StructureChemicalsChemotaxisChronic DiseaseCommunitiesDataDepositionDermalDevelopmentDiseaseEmbryoEnvironmentEnvironmental HealthEnvironmental PollutionEnvironmental Risk FactorEventExperimental Animal ModelExposure toFlow CytometryFoodFrequenciesFutureGoalsHazardous SubstancesHealthHepatotoxicityHumanHuman Cell LineImmuneImmune System DiseasesImmune responseImmune systemImmunizeImmunosuppressionImmunotherapyImpairmentIn VitroIndividualIndustrial ProductIndustrializationInfectionInnate Immune SystemKnowledgeMalignant NeoplasmsMeasuresMediatingMetabolicMetabolismMitochondriaModelingMolecularMusNatural ImmunityNorth CarolinaOrganismOutcomePhagocytesPhagocytosisPlasma CellsProductionPublic HealthReactive Oxygen SpeciesResearchResearch Project GrantsResistanceRespirationRiskSamplingSerumSignal PathwaySignaling ProteinSiteSourceStainsSuperfundT-LymphocyteTestingToxic effectToxicologyUnited StatesUniversitiesWaterWorkZebrafishadaptive immunitybasebioaccumulationconsumer productdevelopmental toxicitydisorder riskdrinking waterexperienceexposed human populationhazardimmune functionimmune healthimmunoregulationimmunotoxicityimprovedin vivoin vivo Modelmacrophagemetabolomemetabolomicsmouse modelneutrophilnovelperfluorooctane sulfonateprogramsrapid techniquereproductive toxicityresponsetooltranscriptomevaccine response
项目摘要
ABSTRACT
(Biomedical Research) Research Project 2
Biomedical Research Project 2 is one of two biomedical research projects proposed for the “Center for
Environmental and Health Effects of PFAS” being led by North Carolina State University (NC State). The primary
goal of the proposed Center is to provide highly relevant data and information to help the Superfund Research
Program (SRP) address the growing problem of per- and polyfluoroalkyl substance (PFAS) contamination across
the United States (US). PFAS are considered contaminants of emerging concern for myriad reasons, but one of
the most pressing is that only a handful of the nearly 5,000 PFAS that are known to exist have been evaluated
for their toxicologic potential, even though numerous communities are being impacted by their presence in
environmental media, especially drinking water. Studies of humans exposed to perfluoroocatonic acid (PFOA)
and perfluorooctane sulfonate (PFOS), two PFAS detected with high frequency and concentration in human and
environmental samples, have provided compelling evidence that the immune system is a sensitive target of
PFAS. Additional work with experimental animal models supports the hypothesis that PFAS induce
immunotoxicity and alter responses of both the adaptive and innate immune systems. While PFOA and PFOS
are presumed to be immune hazards to humans, several gaps in knowledge exist: notably, the mechanism(s)
by which these PFAS induce immunotoxicity remain elusive, and the extent to which most PFAS of emerging
concern perturb immune function is largely unknown. Therefore, the objectives of Project 2 are twofold: i) explore
molecular changes underlying PFAS-induced immunotoxicity in select animal models as well as human cell lines
to identify impacted signaling pathways and networks, and ii) determine the immunotoxicological profile,
including mechanistic underpinnings, of PFAS of emerging concern relative to the few well-studied PFAS. Our
global hypothesis is that PFAS-mediated immune suppression results from modulation of immune cell metabolic
functions. This hypothesis will be evaluated by (Aim 1) quantifying the impact of PFAS exposure on B cell
development and antibody production in a mouse model and (Aim 2) identifying the impact of PFAS exposure
on phagocytotic cell function using a zebrafish in vivo model and human in vitro cell line models. This project will
address significant gaps in what is known about the mechanisms by which PFAS induce immunotoxicity, which
will improve management of a known PFAS health risk, immune suppression, and accelerate development of
immune therapies for affected individuals. Additionally, the large number of untested PFAS also means that
methods for rapid prioritization are critical for informing appropriate regulatory measures; our project will uncover
molecular initiating events underlying altered immune responses to facilitate novel, immune-mechanism-based
prioritization strategies for PFAS recently detected in North Carolina and elsewhere.
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(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 }}
Seth William Kullman其他文献
Seth William Kullman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('Seth William Kullman', 18)}}的其他基金
Uncovering the Mechanisms of PFAS-induced Immunotoxicity
揭示 PFAS 诱导免疫毒性的机制
- 批准号:
10559567 - 财政年份:2022
- 资助金额:
$ 9.71万 - 项目类别:
Uncovering the Mechanisms of PFAS-induced Immunotoxicity
揭示 PFAS 诱导免疫毒性的机制
- 批准号:
10558142 - 财政年份:2020
- 资助金额:
$ 9.71万 - 项目类别:
Uncovering the Mechanisms of PFAS-induced Immunotoxicity
揭示 PFAS 诱导免疫毒性的机制
- 批准号:
10337308 - 财政年份:2020
- 资助金额:
$ 9.71万 - 项目类别:
In vivo Transgenic Reporter for Hepatobiliary Toxicity
肝胆毒性的体内转基因报告基因
- 批准号:
6940651 - 财政年份:2004
- 资助金额:
$ 9.71万 - 项目类别:
In vivo Transgenic Reporter for Hepatobiliary Toxicity
肝胆毒性的体内转基因报告基因
- 批准号:
6840566 - 财政年份:2004
- 资助金额:
$ 9.71万 - 项目类别:
Molecular Pathways to Pathogenesis in Toxicology
毒理学发病机制的分子途径
- 批准号:
10172421 - 财政年份:1977
- 资助金额:
$ 9.71万 - 项目类别:
Molecular Pathways to Pathogenesis in Toxicology
毒理学发病机制的分子途径
- 批准号:
10452637 - 财政年份:1977
- 资助金额:
$ 9.71万 - 项目类别:
Molecular Pathways to Pathogenesis in Toxicology
毒理学发病机制的分子途径
- 批准号:
10626916 - 财政年份:1977
- 资助金额:
$ 9.71万 - 项目类别:
相似海外基金
Single-cell analysis of adaptive immune system cells in IBD patients
IBD 患者适应性免疫系统细胞的单细胞分析
- 批准号:
22KJ2212 - 财政年份:2023
- 资助金额:
$ 9.71万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Antigen presentation to the adaptive immune system in the choroid contributes to ocular autoimmune disease
脉络膜中的适应性免疫系统的抗原呈递导致眼部自身免疫性疾病
- 批准号:
10740465 - 财政年份:2023
- 资助金额:
$ 9.71万 - 项目类别:
Elucidation of the adaptive immune system in teleost fish
阐明硬骨鱼的适应性免疫系统
- 批准号:
22K05824 - 财政年份:2022
- 资助金额:
$ 9.71万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Peripheral Adaptive Immune System Changes Associated with Alzhiemer's Disease
与阿尔茨海默病相关的外周适应性免疫系统变化
- 批准号:
10194864 - 财政年份:2021
- 资助金额:
$ 9.71万 - 项目类别:
Interaction of Galectin-9 and Pregnancy-Specific Glycoprotein 1 in the Regulation of Cells of the Innate and Adaptive Immune System
Galectin-9 和妊娠特异性糖蛋白 1 在先天性和适应性免疫系统细胞调节中的相互作用
- 批准号:
10434937 - 财政年份:2021
- 资助金额:
$ 9.71万 - 项目类别:
Interaction of Galectin-9 and Pregnancy-Specific Glycoprotein 1 in the Regulation of Cells of the Innate and Adaptive Immune System
Galectin-9 和妊娠特异性糖蛋白 1 在先天性和适应性免疫系统细胞调节中的相互作用
- 批准号:
10302501 - 财政年份:2021
- 资助金额:
$ 9.71万 - 项目类别:
Learning a molecular shape space for the adaptive immune system
学习适应性免疫系统的分子形状空间
- 批准号:
10275426 - 财政年份:2021
- 资助金额:
$ 9.71万 - 项目类别:
CAREER: Emergence of Functional Organization in the Adaptive Immune System
职业:适应性免疫系统中功能组织的出现
- 批准号:
2045054 - 财政年份:2021
- 资助金额:
$ 9.71万 - 项目类别:
Continuing Grant
Learning a molecular shape space for the adaptive immune system
学习适应性免疫系统的分子形状空间
- 批准号:
10669709 - 财政年份:2021
- 资助金额:
$ 9.71万 - 项目类别:
Learning a molecular shape space for the adaptive immune system
学习适应性免疫系统的分子形状空间
- 批准号:
10467050 - 财政年份:2021
- 资助金额:
$ 9.71万 - 项目类别: