Project 2: Immune signals promoting pancreas cancer stemness and progression
项目2:促进胰腺癌干性和进展的免疫信号
基本信息
- 批准号:10187126
- 负责人:
- 金额:$ 43.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:Acinar CellAffectCell CommunicationCellsChemoresistanceChronicCommunicationDevelopmentDiseaseDuctal Epithelial CellEarly DiagnosisEnvironmentEpigenetic ProcessExperimental ModelsFeedbackFibroblastsFibrosisGeneticGenetic EngineeringGoalsGrowthHumanImmuneImmune signalingIn VitroInflammationLeadLinkMalignant NeoplasmsMalignant neoplasm of pancreasMediatingMethodsMusNeoplasm MetastasisOncogenicPancreasPancreas TransplantationPancreatic Ductal AdenocarcinomaPancreatic Intraepithelial NeoplasiaPancreatic ductPancreatitisPathway interactionsPatientsPeripheralPharmacologyPhenotypePlatelet-Derived Growth Factor alpha ReceptorPlayPopulationProcessPrognosisPropertyRadiation therapyRecurrenceRegulationResistanceRisk FactorsRoleSTAT3 geneSamplingSignal PathwaySignal TransductionStromal CellsSurvival RateTP53 geneTamoxifenTestingTherapeuticTumorigenicityWorkacute pancreatitisbasecancer cellcancer stem cellcancer subtypescarcinogenesiscell stromachemotherapychronic pancreatitisdriver mutationgenetic approachimmunoregulationimprovedin vivoinsightinterleukin-22molecular targeted therapiesmouse modelnovelpancreatic cancer cellspancreatic ductal adenocarcinoma cellpancreatic ductal adenocarcinoma modelpancreatic stellate cellreceptorselective expressionsingle-cell RNA sequencingstemnesssynergismtherapeutic evaluationtherapeutic targettissue repairtumortumor microenvironmenttumor progressiontumorigenic
项目摘要
ABSTRACT (Project 2)
There is an urgent need to discover improved therapies for pancreatic ductal adenocarcinoma (PDAC), which
require a better understanding of mechanisms underlying development and recurrence. Chronic inflammation
is a feature and an independent risk factor for PDAC. Interactions between immune cells, cancer associated
fibroblasts (CAFs), and cancer cells can promote PDAC development and progression. However, little is
known about how immune cells or immune cell-related signals affect PDAC development. Our long-term goal
is to identify signaling nodes that facilitate the crosstalk between immune cells, cancer cells and CAFs to
promote PDAC progression. In healthy subjects, IL-22 is expressed by immune cells while its receptor, IL-
22RA1, is selectively expressed in non-immune cells. IL-22 and IL-22RA1 expression are both elevated in
PDAC, but little is known about the role of this signaling axis in PDAC. We have recently demonstrated high,
heterogeneous expression of IL-22RA1 in human and mouse PDAC. Importantly, high IL-22RA1 expression is
associated with poor prognosis of PDAC patients. Furthermore, we showed that IL-22RA1high cells in PDAC
have cancer stem cell properties, including high tumorigenicity in vivo. We found that IL-22 stimulates IL-
22RA1 expression through STAT3 activation in PDAC cells, and postulate that this positive feedback loop
enhances stemness and tumorigenicity of PDAC cancer cells. Thus, IL-22RA1/STAT3 signaling might provide
a therapeutic target to treat PDAC with high IL-22RA1. We will use different mouse models of PDAC to study
the effects of genetic deletion of IL-22RA1 in acinar cells or PSCs on PDAC growth, metastasis, and stemness
in vivo. We will use novel, multi- dimensional analysis methods to analyze if inflammation drives
carcinogenesis via IL-22, IL-22 expression in immune cell populations in PDAC mouse models and test
therapeutic benefit of blocking IL-22 signaling in PDAC using pharmacologic and genetic approaches. We will
determine the expression and role of IL-22/IL-22RA1 axis in human PDAC. Using primary human pancreatic
ductal epithelial cells with defined PDAC genetic driver mutations, we will study the contribution and regulation
of IL-22/IL-22RA1 signaling in human PDAC development.
Our proposed studies will novel insights into how genetic drivers and inflammation orchestrate
functional connection and communication between immune and non-immune components in PDAC. Further,
we will gain mechanistic understanding of how (1) immune cell, CAF, and cancer cell interactions mediated by
the IL-22/IL-22RA1 axis lead to PDAC development and (2) inhibition of the IL-22/IL-22RA1 signaling axis
provides a therapeutic strategy that targets cancer stemness, a major factor in therapy resistance and the
dismal prognosis associated with PDAC.
摘要(项目二)
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 }}
Mara H. Sherman其他文献
Regulating MYC translation in cancer
在癌症中调节 MYC 翻译
- DOI:
10.1038/s41556-024-01589-3 - 发表时间:
2025-02-07 - 期刊:
- 影响因子:19.100
- 作者:
Zainab Hussain;Mara H. Sherman - 通讯作者:
Mara H. Sherman
Mara H. Sherman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('Mara H. Sherman', 18)}}的其他基金
Identifying and Targeting Metabolic Dependencies in the Pancreatic Tumor Microenvironment
识别和靶向胰腺肿瘤微环境中的代谢依赖性
- 批准号:
10733637 - 财政年份:2023
- 资助金额:
$ 43.59万 - 项目类别:
Origins and functions of pancreatic cancer-associated fibroblasts
胰腺癌相关成纤维细胞的起源和功能
- 批准号:
10611388 - 财政年份:2023
- 资助金额:
$ 43.59万 - 项目类别:
Origins and functions of pancreatic cancer-associated fibroblasts
胰腺癌相关成纤维细胞的起源和功能
- 批准号:
10737898 - 财政年份:2023
- 资助金额:
$ 43.59万 - 项目类别:
Origins and functions of pancreatic cancer-associated fibroblasts
胰腺癌相关成纤维细胞的起源和功能
- 批准号:
10201935 - 财政年份:2021
- 资助金额:
$ 43.59万 - 项目类别:
Origins and functions of pancreatic cancer-associated fibroblasts
胰腺癌相关成纤维细胞的起源和功能
- 批准号:
10378681 - 财政年份:2021
- 资助金额:
$ 43.59万 - 项目类别:
Identifying and Targeting Metabolic Dependencies in the Pancreatic Tumor Microenvironment
识别和靶向胰腺肿瘤微环境中的代谢依赖性
- 批准号:
9811945 - 财政年份:2018
- 资助金额:
$ 43.59万 - 项目类别:
Identifying and Targeting Metabolic Dependencies in the Pancreatic Tumor Microenvironment
识别和靶向胰腺肿瘤微环境中的代谢依赖性
- 批准号:
10411398 - 财政年份:2018
- 资助金额:
$ 43.59万 - 项目类别:
Fatty acid signaling in the pancreatic tumor microenvironment
胰腺肿瘤微环境中的脂肪酸信号传导
- 批准号:
10728646 - 财政年份:2018
- 资助金额:
$ 43.59万 - 项目类别:
Identifying and Targeting Metabolic Dependencies in the Pancreatic Tumor Microenvironment
识别和靶向胰腺肿瘤微环境中的代谢依赖性
- 批准号:
10440274 - 财政年份:2018
- 资助金额:
$ 43.59万 - 项目类别:
Identifying and Targeting Metabolic Dependencies in the Pancreatic Tumor Microenvironment
识别和靶向胰腺肿瘤微环境中的代谢依赖性
- 批准号:
10186710 - 财政年份:2018
- 资助金额:
$ 43.59万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 43.59万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 43.59万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 43.59万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 43.59万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 43.59万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 43.59万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 43.59万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 43.59万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 43.59万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 43.59万 - 项目类别:
Grant-in-Aid for Early-Career Scientists