The mutational mechanisms shaping melanocytes in human skin

塑造人类皮肤黑素细胞的突变机制

基本信息

项目摘要

Project Summary/Abstract As a barrier organ, skin forms the main defense against ultraviolet (UV) radiation, a potent mutagen emitted by the sun. The mutational damage incurred through this role can lead to melanoma, the deadliest form of skin cancer. Contrary to expectations, melanoma is more common on body sites that are only exposed to UV radiation intermittently, such as the back and shoulder, rather than body sites exposed more continuously, such as the head/neck areas. We recently reported the first catalogue of somatic mutations in melanocytes from normal human skin and discovered that melanocytes from the back/trunk had higher mutation burdens than donor-matched melanocytes from the head/neck areas. Based on our mutational observations and the anatomic patterns of melanoma, we hypothesize that melanocytes on the head/neck areas have evolved mechanisms to accumulate mutations more slowly than melanocytes from other body sites – likely an adaptation to counterbalance the higher levels of cumulative sun exposure affecting those sites. If true, this would alter prevention strategies. Moreover, a better understanding of the mechanisms by which melanocytes accumulate mutations would reveal molecular strategies to slow down this process and reduce the incidence of melanoma. We will test our hypothesis in aim 1 by comparing somatic mutations in melanocytes of different anatomic origins within-people and in aim 2 by cataloguing somatic mutations in site-matched melanocytes across people who offer detailed histories of sun exposure. These studies will offer correlative data implicating the main factors driving up the mutation burdens in melanocytes. A major obstacle to these studies is that it is difficult to measure somatic mutations in individual cells at a high degree of accuracy. However, we recently pioneered a workflow to call mutations in individual melanocytes at nearly 100% specificity and sensitivity. To complement these observational studies, in aim 3, we will measure in vitro the rates at which melanocytes of different anatomic origins repair DNA damage and dissect the main mechanisms regulating this process. Towards this goal, we have developed assays to measure UV-radiation-induced DNA damage at single base- pair resolution in tissue-cultured cells. Taken together, the scientific approaches employed in this proposal are technologically innovative and will illuminate the mutational mechanisms operating on melanocytes in normal human skin, addressing major gaps in knowledge that have vexed the skin research community.
项目总结/文摘

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 }}

Alan Hunter Shain其他文献

Alan Hunter Shain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('Alan Hunter Shain', 18)}}的其他基金

The genomic landscape and evolution of cutaneous squamous cell carcinoma
皮肤鳞状细胞癌的基因组景观和进化
  • 批准号:
    10709592
  • 财政年份:
    2022
  • 资助金额:
    $ 42.67万
  • 项目类别:
Defining the role of SWI/SNF chromatin remodeling complex mutations during melanoma progression
定义 SWI/SNF 染色质重塑复合体突变在黑色素瘤进展过程中的作用
  • 批准号:
    9367641
  • 财政年份:
    2018
  • 资助金额:
    $ 42.67万
  • 项目类别:
Defining the role of SWI/SNF chromatin remodeling complex mutations during melanoma progression
定义 SWI/SNF 染色质重塑复合体突变在黑色素瘤进展过程中的作用
  • 批准号:
    10468456
  • 财政年份:
    2018
  • 资助金额:
    $ 42.67万
  • 项目类别:

相似海外基金

Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
  • 批准号:
    495182
  • 财政年份:
    2023
  • 资助金额:
    $ 42.67万
  • 项目类别:
Parkinson's disease and aging affect neural activation during continuous gait alterations to the split-belt treadmill: An [18F] FDG PET Study.
帕金森病和衰老会影响分体带跑步机连续步态改变期间的神经激活:[18F] FDG PET 研究。
  • 批准号:
    400097
  • 财政年份:
    2019
  • 资助金额:
    $ 42.67万
  • 项目类别:
The elucidation of the mechanism by which intestinal epithelial cells affect impaired glucose tolerance during aging
阐明衰老过程中肠上皮细胞影响糖耐量受损的机制
  • 批准号:
    19K09017
  • 财政年份:
    2019
  • 资助金额:
    $ 42.67万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Does aging of osteocytes adversely affect bone metabolism?
骨细胞老化会对骨代谢产生不利影响吗?
  • 批准号:
    18K09531
  • 财政年份:
    2018
  • 资助金额:
    $ 42.67万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Links between affect, executive function, and prefrontal structure in aging: A longitudinal analysis
衰老过程中情感、执行功能和前额叶结构之间的联系:纵向分析
  • 批准号:
    9766994
  • 财政年份:
    2018
  • 资助金额:
    $ 42.67万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9320090
  • 财政年份:
    2017
  • 资助金额:
    $ 42.67万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    10166936
  • 财政年份:
    2017
  • 资助金额:
    $ 42.67万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9761593
  • 财政年份:
    2017
  • 资助金额:
    $ 42.67万
  • 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
  • 批准号:
    9925164
  • 财政年份:
    2016
  • 资助金额:
    $ 42.67万
  • 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
  • 批准号:
    9345997
  • 财政年份:
    2016
  • 资助金额:
    $ 42.67万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了