CAREER: Cancer-associated secondary lymphedema on-chip

职业:芯片上癌症相关继发性淋巴水肿

基本信息

  • 批准号:
    2338610
  • 负责人:
  • 金额:
    $ 60万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2024
  • 资助国家:
    美国
  • 起止时间:
    2024-04-01 至 2029-03-31
  • 项目状态:
    未结题

项目摘要

Lymphedema is swelling caused by poor lymphatic drainage. In the US, breast cancer patients show a high incidence of lymphedema in their arms. The goals of this CAREER project are to comprehend the regulation of the lymphatic structure and function in breast cancer and to discover novel approaches to treating lymphedema linked to breast cancer through the establishment of a unique cell culture platform dedicated to studying lymphatic drainage in breast cancer. This project may contribute to the development of new therapies benefitting millions of lymphedema patients and enhancing health outcomes in the US. Educational initiatives involving Cornell and local high school students are aligned with the research goals. The recruitment and training of a diverse group of underrepresented undergraduate students will be carried out through Cornell Engineering Learning Initiatives and the Prefreshman Summer Program. Collaborations with New Visions Engineering and the Cornell Science and Technology Entry Program will further engage disadvantaged high school students in hands-on activities related to lymphatic research. Additionally, the project's educational program will create online courses to raise scientific awareness of lymphatic diseases.Lymphedema, characterized by swelling due to impaired lymphatic drainage, affects over 150 million patients worldwide. Despite its prevalence, there is no FDA-approved treatment, and commonly used conservative therapies provide primarily palliative relief. This CAREER project seeks to investigate the mechanisms of lymphedema, identifying potential therapeutic targets and treatment strategies. While genetic defects can cause primary lymphedema, secondary lymphedema, particularly breast cancer-associated secondary lymphedema, is more common. However, the mechanistic understanding of breast cancer-associated secondary lymphedema is currently limited. The lack of experimental models for normal and impaired lymphatic drainage has been a significant obstacle. The principal investigator addresses this challenge with a microfluidic culture model featuring an engineered lymphatic vessel that mimics key lymphatic endothelial cell-cell junctions. These junctions are crucial for facilitating lymphatic drainage and allow for the study of how they are affected in conditions such as breast cancer. The project extends this work by creating tissue-engineered co-culture models replicating the breast tumor lymphatic microenvironment. These models involve culturing multiple breast tumor cells and lymphatic cells in a well-defined three-dimensional space outside living organisms. A pilot study revealed that triple-negative breast cancer cells impact lymphatic structure and function, leading to impaired drainage. The research is organized into two specific aims: Aim 1 focuses on understanding the regulation of lymphatic junction structure and drainage function in breast cancer and Aim 2 centers on the treatment of breast cancer-associated secondary lymphedema. In conjunction with educational outreach, this CAREER project will contribute to the development of new therapies for lymphedema patients in the US and will enhance scientific awareness of lymphatic disease and microphysiological systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
淋巴水肿是淋巴引流不良引起的肿胀。在美国,乳腺癌患者手臂淋巴水肿的发生率很高。这个职业项目的目标是了解乳腺癌淋巴结构和功能的调节,并通过建立一个致力于研究乳腺癌淋巴引流的独特细胞培养平台,发现治疗与乳腺癌有关的淋巴水肿的新方法。该项目可能有助于开发新的治疗方法,使数百万淋巴水肿患者受益,并改善美国的健康状况。涉及康奈尔大学和当地高中生的教育倡议与研究目标保持一致。将通过康奈尔工程学习计划和普雷赫曼暑期计划,招募和培训不同群体的人数不足的本科生。与新视野工程和康奈尔科技入门计划的合作将进一步吸引处于不利地位的高中生参与与淋巴研究相关的动手活动。此外,该项目的教育计划将创建在线课程,以提高人们对淋巴疾病的科学认识。淋巴水肿的特征是淋巴排出障碍导致肿胀,影响着全球超过1.5亿患者。尽管它很流行,但没有FDA批准的治疗方法,常用的保守疗法主要是姑息治疗。这个职业项目旨在研究淋巴水肿的机制,确定潜在的治疗靶点和治疗策略。虽然遗传缺陷会导致原发性淋巴水肿,但继发性淋巴水肿,特别是乳腺癌相关的继发性淋巴水肿更为常见。然而,目前对乳腺癌相关继发性淋巴水肿的机制了解有限。缺乏正常和受损淋巴引流的实验模型一直是一个重大障碍。首席研究人员通过微流控培养模型解决了这一挑战,该模型以工程淋巴管为特色,模仿关键的淋巴管内皮细胞-细胞连接。这些连接对促进淋巴引流至关重要,并有助于研究它们在乳腺癌等情况下是如何受到影响的。该项目通过创建复制乳腺肿瘤淋巴微环境的组织工程共培养模型来扩展这项工作。这些模型包括在活体外一个清晰的三维空间中培养多个乳腺肿瘤细胞和淋巴细胞。一项初步研究显示,三阴性乳腺癌细胞会影响淋巴结构和功能,导致引流功能受损。这项研究有两个特定的目标:目标1专注于了解乳腺癌淋巴连接结构和引流功能的调节,目标2专注于乳腺癌相关继发性淋巴水肿的治疗。与教育外展相结合,这一职业项目将有助于为美国淋巴水肿患者开发新的治疗方法,并将提高对淋巴疾病和微生理系统的科学认识。该奖项反映了NSF的法定使命,并通过使用基金会的智力优势和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

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Esak Lee其他文献

Non-canonical ALK7 pathways promote pancreatic cancer metastasis through β-catenin/MMP-mediated basement membrane breakdown and intravasation
  • DOI:
    10.1186/s12943-025-02384-w
  • 发表时间:
    2025-07-04
  • 期刊:
  • 影响因子:
    33.900
  • 作者:
    Anna M. Kolarzyk;Yujin Kwon;Elizabeth Oh;Keng-Jung Lee;Su-Yeon Cho;Issahy Cano;Renhao Lu;Tae Joon Kwak;Jaehyun Lee;Gigi Wong;Andrew H. Kim;Omar Gandarilla;Manuel Hidalgo;Won Kyu Kim;Esak Lee
  • 通讯作者:
    Esak Lee
Biomimetic Microsystems for Blood and Lymphatic Vascular Research
用于血液和淋巴管研究的仿生微系统
  • DOI:
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    D. Nguyen;Esak Lee
  • 通讯作者:
    Esak Lee
In vitro modeling of tumor spheroid interactions to perfused blood vessels
肿瘤球体与灌注血管相互作用的体外建模
  • DOI:
    10.1101/2020.08.03.234633
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    T. Kwak;Esak Lee
  • 通讯作者:
    Esak Lee

Esak Lee的其他文献

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相似国自然基金

中国北方人群肺癌患者Cancer/Testis抗原表达谱绘制表位鉴定及功能性抗原特异性CTL制备研究
  • 批准号:
    81673007
  • 批准年份:
    2016
  • 资助金额:
    54.0 万元
  • 项目类别:
    面上项目

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