Detection of Emergent Mechanical Properties of Biologically Complex Cellular States

生物复杂细胞状态的紧急机械特性的检测

基本信息

批准号：
10832871
负责人：
Mark A LaBarge
金额：
$ 13.73万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10832871
关键词：
3-Dimensional Address African American African ancestry Androgen Receptor Apoptosis Apoptosis Regulation Gene Apoptotic Applications Grants Binding Binding Proteins Biology Breast Cancer Patient Breast Cancer Risk Factor Breast Cancer cell line Cancer Biology Cells Centrosome Cessation of life Chromosomal Instability Chromosome Segregation Clinical Complex Data Data Set Detection Disease Disease Progression ERBB2 gene Family member Future Gene Expression Genes Genetic Transcription Genomic Instability Goals Kinesin Malignant Neoplasms Mechanics Mediating Microtubules Mitosis Modeling Normal Cell Nuclear Patients Phenotype Pre-Clinical Model Proliferating Property Proteins Publishing Race Resistance Signal Transduction TCF7L2 gene Therapeutic Intervention Tissues Woman aggressive breast cancer beta catenin cancer cell cancer subtypes cancer survival career development cohort daughter cell human data mRNA Expression malignant breast neoplasm mechanical properties migration parent grant pharmacologic protein expression racial disparity receptor binding receptor expression therapeutic target triple-negative invasive breast carcinoma

项目摘要

Abstract: This is a Diversity Supplement to R01EB024989 for Career Development of Dr. Nikita Jinna. The parent grant application aims to investigate cell-state and tissue properties that increase risk for breast cancer - particularly triple negative breast cancer (ER-, PR-, HER2-wild type (wt); TNBC). Here Dr. Jinna will investigate the biology of a highly aggressive subtype of ER/PR- breast cancer, that disproportionately impacts women of African ancestry. Quadruple negative breast cancer (ER-, PR-, HER2-wt, AR-; QNBC) has now surpassed TNBC as the most aggressive breast cancer subtype1. In addition to lacking expression of the actionable breast cancer targets, ER, PR, and HER2 in TNBC, QNBCs also lack expression of the actionable androgen receptor (AR) target. Additionally, QNBC disproportionately afflicts and impacts women of African ancestry, which is contributing to the overall racially disparate burden in breast cancer. Thus, alternative actionable targets in QNBC are urgently needed to address this new clinical challenge. In my preliminary data, obtained in two independent clinical and four independent gene-expression datasets, the centrosome clustering protein, kinesin family member C1 (KIFC1) is upregulated in QNBCs (vs. TNBC). The goal of this proposal is to investigate KIFC1 as a driver of aggressive QNBC biology and potential therapeutic target for QNBC patients. Here, Dr. Jinna will determine how AR-loss promotes aggressive QNBC biology in preclinical models developed by Dr. Mark La Barge for future therapeutic intervention.

抽象的：这是 R01EB024989 的多元化补充，用于 Nikita Jinna 博士的职业发展。这家长资助申请旨在调查增加风险的细胞状态和组织特性乳腺癌 - 特别是三阴性乳腺癌（ER-、PR-、HER2-野生型 (wt)；TNBC）。 Jinna 博士将在此研究高度侵袭性 ER/PR 乳腺癌亚型的生物学，这对非洲裔妇女的影响尤为严重。四阴性乳腺癌（ER-、PR-、HER2-wt、AR-；QNBC）现已超过 TNBC，成为最具侵袭性的乳腺疾病癌症亚型1。除了缺乏可操作的乳腺癌靶标 ER 的表达外， TNBC、QNBC 中的 PR 和 HER2 也缺乏可作用雄激素受体 (AR) 的表达目标。此外，QNBC 不成比例地折磨和影响非洲血统的女性，这加剧了乳腺癌的总体种族负担。因此，替代 QNBC 迫切需要可操作的目标来应对这一新的临床挑战。在我的初步数据，在两次独立临床和四次独立基因表达中获得数据集显示，中心体聚类蛋白、驱动蛋白家族成员 C1 (KIFC1) 在 QNBC（与 TNBC）。该提案的目标是调查 KIFC1 作为攻击性驱动因素 QNBC 生物学和 QNBC 患者的潜在治疗靶点。在这里，金娜博士将确定在 Mark La 博士开发的临床前模型中，AR 丢失如何促进积极的 QNBC 生物学为未来的治疗干预提供驳船。