Fibrotic extracellular matrix: uncovering its role in breast cancer genome stability and metabolic plasticity

纤维化细胞外基质:揭示其在乳腺癌基因组稳定性和代谢可塑性中的作用

基本信息

  • 批准号:
    10507566
  • 负责人:
  • 金额:
    $ 11.02万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-15 至 2027-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT ABSTRACT The candidate, Dr. Elizabeth Moore, seeks the proposed Mentored Research Scientist Development Award (K01) to acquire the necessary training and experience to become an independent translational clinician- scientist focusing on tumor microenvironmental regulation of breast cancer (BC) genome stability and therapeutic resistance. BC therapeutic resistance remains a major hindrance to successful treatment, particularly in the aggressive triple negative (TNBC) subtype. However, it remains unclear how therapeutic response is influenced by the physical and biological characteristics of the tumor microenvironment and which role altered DNA damage response (DDR) mechanisms and metabolic reprogramming play this process. In particular, it remains to be elucidated how fibrotic remodeling of the extracellular matrix (ECM), which is a hallmark feature of a protumorigenic microenvironment, impact BC risk and drug resistance. Given these connections, the overall objective of the proposed studies will be to identify mechanisms of matrix-mediated BC therapeutic resistance. Aim 1 will determine the impact of fibrotic ECM on BC DNA damage response (DDR). Aim 2 will test how fibrotic ECM regulates the DDR and metabolism of tumor cells and their reciprocal interactions. Aim 3 will test the functional links between fibrotic ECM, DDR, and metabolism in vivo. Aims 1 and 2 will utilize translationally relevant, high fidelity 3D tissue culture systems in which features of fibrotic ECM remodeling can be selectively adjusted. Aim 3 will leverage a humanized mouse model of mammary fibrosis and TNBC using human BC cell lines and patient derived xenografts of TNBC. A multidisciplinary approach, including classic molecular techniques, gene expression analyses, metabolomics and Seahorse metabolic analyses, and advanced imaging will be applied to achieve these aims and for the candidate to acquire additional technical skills. Dr. Moore’s mentor is a leading expert in engineering in vitro and in vivo models to study tumor-microenvironment interactions. Co-mentors will provide expertise in the fields of genome stability and the DDR, cellular metabolism and metabolomics, and clinical aspects of breast cancer. Faculty expertise and interdisciplinary collaboration in oncology research is exceptionally strong at Cornell University and further strengthened by the training environment and exceptional core facilities. The planned career development activities, including technical research training, coursework, attendance of seminars and conferences, experience in grant and manuscript preparation, and the refinement of teaching, mentorship, and laboratory management skills will support Dr. Moore’s transition to independence. The incorporation of physical and life science approaches, utilization of highly translational in vitro and in vivo platforms, and the integration of both extracellular and intracellular regulation of BC genome stability will enable Dr. Moore to establish a niche in oncology research. Proposed activities will generate data for a future R01 application and launch Dr. Moore’s faculty career in advancing the field of breast cancer biology with the goal to improve patient prognosis.
项目摘要

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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Elizabeth S Moore其他文献

Effect of Occupational Therapy in Promoting Medication Adherence in Primary Care: A Randomized Controlled Trial.
职业治疗在促进初级保健中药物依从性方面的作用:一项随机对照试验。

Elizabeth S Moore的其他文献

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{{ truncateString('Elizabeth S Moore', 18)}}的其他基金

Fibrotic extracellular matrix: uncovering its role in breast cancer genome stability and metabolic plasticity
纤维化细胞外基质:揭示其在乳腺癌基因组稳定性和代谢可塑性中的作用
  • 批准号:
    10655647
  • 财政年份:
    2022
  • 资助金额:
    $ 11.02万
  • 项目类别:

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