Detection of Emergent Mechanical Properties of Biologically Complex Cellular States

摘要： 这是R 01 EB 024989的多元化补充，用于Nikita Jinna博士的职业发展。的 父母补助金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-、HER 2-野生型（wt）; TNBC）。 在这里，Jinna博士将研究ER/PR的一种高度侵袭性亚型-乳腺癌的生物学， 对非洲裔女性的影响尤为严重。四阴性乳腺癌 (ER-、PR-、HER 2-wt、AR-; QNBC）现已超过TNBC成为最具攻击性的乳腺癌 癌症亚型1.除了缺乏可操作的乳腺癌靶点ER的表达外， PR和HER 2，QNBCs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妇女， 这导致了乳腺癌的总体种族差异负担。因此，替代 迫切需要QNBC中的可操作目标来应对这一新的临床挑战。在我 初步数据，在两个独立的临床和四个独立的基因表达， 数据集，中心体聚集蛋白，驱动蛋白家族成员C1（KIFC 1）在 QNBCs（与TNBC）。该提案的目标是调查KIFC 1作为积极的驱动因素， QNBC生物学和QNBC患者的潜在治疗靶点。在这里，金纳博士将决定 AR损失如何促进Mark La博士开发的临床前模型中的侵袭性QNBC生物学 为未来的治疗干预做准备。

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.