Molecular Drivers of Elevated Gallbladder Cancer Incidence in New Mexico

新墨西哥州胆囊癌发病率升高的分子驱动因素

基本信息

项目摘要

Project Summary: Gallbladder Cancer (GBC) is the fifth most common malignancy of the GI tract and the most common in the human biliary tree. Approximately 4,000-5,000 new cases of GBC are diagnosed in the United States annually. Survival outcomes are dismal with only ~8% 5-year survival rate, making it one of the deadliest cancers. GBC has a distinct geographical incidence pattern with global hotspots. These hotspots include countries like Chile, Bolivia, India and the state of New Mexico (NM) in the United States. GBC incidence is abnormally high among the “minority-majority” Native Americans (5-8 fold higher) and Hispanics (2-4 fold higher) compared to Caucasians living in New Mexico. The reasons underlying GBC incidence disparities in NM is unknown and there are critical gaps in our understanding of gallbladder carcinogenesis. We postulate environmental heavy metal exposure is the key risk factor responsible for GBC disparities seen among minorities of NM. The southwestern United States (NM, AZ, UT and NV) has a long environmental legacy of abandoned heavy metal mines. These mines are usually found in close proximity to a significant number of socio-economically disadvantaged Native American and Hispanic communities of NM. To prove our GBC hypothesis, we propose the use of New Mexican patient derived gallbladder epithelial cell lines in this proposal. Aim 1 will use post-surgical gallbladder samples to determine the somatic mutational landscapes and key molecular drivers of GBC in an ethnicity and gender dependent manner. Aim 2 will determine the impact of exposures of two metals of significance in New Mexico, uranium and cadmium, on the GB phosphoproteomic cell signaling dysregulation. In particular, we will focus on the role of metal exposure driven PI3K-Akt and MAPK signaling pathway alterations. Aim 3 will determine the effects of cadmium and uranium exposure on gallbladder epithelial barrier disruption and wound healing as a mechanistic explanation of GBC disparities seen in NM. Aim 3 will confirm, for the first time, the role of metal induced disruption of the GB epithelial barrier causing chronic transmural inflammation which is a well-known prerequisite of gallbladder carcinogenesis. Our long-term goal is to understand the molecular mechanisms of gallbladder carcinogenesis using innovative, high-throughput bioinformatics approaches. This basic science proposal deeply informs the translational clinical initiatives currently underway in our lab. Finally, this proposal will also provide a firm scientific basis to enable preventative, population based screening measures to alleviate GBC disparities seen in Native American and Hispanic communities of New Mexico.
项目总结: 胆囊癌(GBC)是胃肠道第五大常见恶性肿瘤,也是 人类的胆汁树。美国约有4,000-5,000例新确诊的胆囊癌病例 每年一次。生存结果令人沮丧,5年存活率只有8%左右,使其成为最致命的之一 癌症。GBC具有明显的地理发病模式,具有全球热点。这些热点包括 智利、玻利维亚、印度和美国新墨西哥州等国。GBC发病率为 少数族裔占多数的美洲原住民(高出5-8倍)和拉美裔(高出2-4倍)的比例异常高 与居住在新墨西哥州的高加索人相比)。年GBC发病率差异的原因 NM是未知的,在我们对胆囊癌发生的理解上存在着严重的差距。 我们推测环境中的重金属暴露是造成GBC差异的关键风险因素 在新墨西哥州的少数民族中可见。美国西南部(新墨西哥州、亚利桑那州、德克萨斯州和北卡罗来纳州)有着悠久的环境 废弃的重金属矿留下的遗产。这些地雷通常位于一个重要的矿场附近。 新墨西哥州处于社会经济不利地位的美国原住民和西班牙裔社区的数量。为了证明我们的 GBC假说,我们建议使用新的墨西哥患者来源的胆囊腺上皮细胞系 求婚。目标1将使用手术后的胆囊样本来确定体细胞突变情况和 GBC的关键分子驱动因素以种族和性别依赖的方式。目标2将确定 新墨西哥州两种重要金属铀和镉对GB磷酸蛋白质组的暴露 细胞信号失控。特别是,我们将重点关注金属暴露驱动的PI3K-Akt和 MAPK信号通路改变。目标3将确定镉和铀暴露对 胆囊壁上皮屏障破坏和伤口愈合是胆囊癌差异的机制解释 在新墨西哥州看到的。目标3将首次证实金属诱导的GB上皮屏障破坏的作用 引起慢性跨壁炎症,这是众所周知的胆囊癌发生的先决条件。 我们的长期目标是了解胆囊癌发生的分子机制。 创新的、高通量的生物信息学方法。这一基础科学建议深刻地告知 我们实验室目前正在进行转译临床倡议。最后,这项提议还将提供一个坚定的 实现预防性、基于人群的筛查措施以缓解GBC差异的科学依据 在新墨西哥州的美洲原住民和西班牙裔社区。

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 }}

Rama Gullapalli其他文献

Rama Gullapalli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('Rama Gullapalli', 18)}}的其他基金

Molecular Drivers of Elevated Gallbladder Cancer Incidence in New Mexico
新墨西哥州胆囊癌发病率升高的分子驱动因素
  • 批准号:
    10629366
  • 财政年份:
    2020
  • 资助金额:
    $ 26.34万
  • 项目类别:
Molecular Drivers of Elevated Gallbladder Cancer Incidence in New Mexico
新墨西哥州胆囊癌发病率升高的分子驱动因素
  • 批准号:
    10408035
  • 财政年份:
    2020
  • 资助金额:
    $ 26.34万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 26.34万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了