Determining Age-Dependent Metabolic Changes in Tumors and Their Microenvironment
确定肿瘤及其微环境中年龄依赖性代谢变化
基本信息
- 批准号:10245780
- 负责人:
- 金额:$ 134.48万
- 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:2021-09-21 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAgeAgingAnimal ModelAreaCellsDietEnvironmental ImpactEnvironmental Risk FactorEventHeterogeneityImmune systemKnowledgeLeadMalignant NeoplasmsMetabolicMetabolismNeoplasm MetastasisNutrientOncogenicRisk FactorsScienceTimeage relatedcancer initiationcarcinogenesiscombinatorialdietaryimprovedjuvenile animalmetaplastic cell transformationmicrobialmicrobiomeneoplastic cellresponsesingle cell technologytumortumor growthtumor microenvironmenttumor progression
项目摘要
Title: Determining Age-Dependent Metabolic Changes in Tumors and Their Microenvironment
Project science areas: 6 MCB, 8 HIB
Project Summary/Abstract:
Aging is one of the primary risk factors for cancer and deregulated metabolism is a unifying hallmark for
both aging and cancer. Yet, we do not fully understand how ageassociated metabolic changes contribute to
cancer initiation and progression. Although many animal models are created to fatefully recapitulate the
oncogenic events that lead to cellular transformation and cancer progression, most are carried out in young
animals that likely have metabolically different tumor microenvironments and robust immune systems. To this
date, few studies have systematically examined how age-dependent alterations of cellular and organismal
metabolism impact tumor growth and metastasis. We hypothesize that age-associated metabolic dysregulation
will significantly alter cellular metabolism both within tumor cells, as well as in cells within the tumor
microenvironment, which may influence cancer progression and response to therapies. We propose a
multipronged, single cell approach to characterize and resolve metabolic changes over time, both within the
tumor and its microenvironment. Finally, we will assess the impact of environmental factors, such as dietary
nutrients and microbiome derived metabolites, on cancer initiation and progression. Collectively, we think our
findings will be transformative and will answer key questions of how aging rewires cellular metabolism and how
it affects tumor growth and metastasis. We hope to elucidate important questions about cellular plasticity,
metabolic heterogeneity and identify metabolic liabilities that can be accentuated by limiting specific nutrients or
metabolites in new combinatorial therapies.
标题:确定肿瘤及其微环境中的β-依赖性代谢变化
项目科学领域:6个MCB,8个HIB
项目概要/摘要:
衰老是癌症的主要危险因素之一,代谢失调是癌症的统一标志。
衰老和癌症然而,我们并不完全了解与年龄相关的代谢变化如何有助于
癌症的发生和发展。尽管许多动物模型被创造出来,
导致细胞转化和癌症进展的致癌事件,大多数发生在年轻人中,
这些动物可能具有代谢不同的肿瘤微环境和强大的免疫系统。本
迄今为止,很少有研究系统地研究了细胞和生物体的年龄依赖性变化是如何发生的。
代谢影响肿瘤生长和转移。我们假设年龄相关的代谢失调
将显著改变肿瘤细胞内以及肿瘤内细胞的细胞代谢
微环境,这可能会影响癌症的进展和对治疗的反应。我们提出了一个
多管齐下的单细胞方法来表征和解决随时间推移的代谢变化,
肿瘤及其微环境最后,我们将评估环境因素的影响,如饮食
营养素和微生物组衍生的代谢物,对癌症的发生和发展。总体而言,我们认为
这些发现将是变革性的,并将回答衰老如何重新连接细胞代谢以及如何改变细胞代谢的关键问题。
它影响肿瘤生长和转移。我们希望阐明细胞可塑性的重要问题,
代谢异质性,并确定代谢负债,可以通过限制特定的营养素或
新的组合疗法中的代谢物。
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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Maria M. Mihaylova其他文献
When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging
当卡路里不仅仅是卡路里时:饮食质量和时间作为新陈代谢和健康衰老的调节因素
- DOI:
10.1016/j.cmet.2023.06.008 - 发表时间:
2023-07-11 - 期刊:
- 影响因子:30.900
- 作者:
Maria M. Mihaylova;Amandine Chaix;Mirela Delibegovic;Jon J. Ramsey;Joseph Bass;Girish Melkani;Rajat Singh;Zheng Chen;William W. Ja;Michele Shirasu-Hiza;Mary N. Latimer;Julie A. Mattison;Anna E. Thalacker-Mercer;Vishwa Deep Dixit;Satchidananda Panda;Dudley W. Lamming - 通讯作者:
Dudley W. Lamming
Reaching for more: How reproduction transforms the maternal intestine
追求更多:繁殖如何改变母体肠道
- DOI:
10.1016/j.cell.2025.04.024 - 发表时间:
2025-05-15 - 期刊:
- 影响因子:42.500
- 作者:
Maria H. Festing;Kubra B. Akkaya-Colak;Maria M. Mihaylova - 通讯作者:
Maria M. Mihaylova
Sa025 THE IMPACT OF BARIATRIC SURGERY ON COLORECTAL CANCER RISK: A MATCHED ANALYSIS USING A NATIONWIDE U.S. COHORT
- DOI:
10.1016/s0016-5085(21)01656-5 - 发表时间:
2021-05-01 - 期刊:
- 影响因子:
- 作者:
Hisham Hussan;Samuel Akinyeye;Maria M. Mihaylova;Eric McLaughlin;chienwei chiang;David A. Lieberman - 通讯作者:
David A. Lieberman
Maria M. Mihaylova的其他文献
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{{ truncateString('Maria M. Mihaylova', 18)}}的其他基金
Understanding the Mechanisms of Age-Dependent Decline of Intestinal Stem Cell Function
了解肠道干细胞功能随年龄下降的机制
- 批准号:
9791147 - 财政年份:2018
- 资助金额:
$ 134.48万 - 项目类别:
Understanding the Mechanisms of Age-Dependent Decline of Intestinal Stem Cell Function
了解肠道干细胞功能随年龄下降的机制
- 批准号:
9531224 - 财政年份:2017
- 资助金额:
$ 134.48万 - 项目类别:
Understanding the Mechanisms of Age-Dependent Decline of Intestinal Stem Cell Function
了解肠道干细胞功能随年龄下降的机制
- 批准号:
9385401 - 财政年份:2017
- 资助金额:
$ 134.48万 - 项目类别:
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