Detection of Emergent Mechanical Properties of Biologically Complex Cellular States

摘要： 这是尼基塔·金纳博士职业发展R01EB024989的多样性补充。这个 父母拨款申请旨在调查增加癌症风险的细胞状态和组织属性 乳腺癌--尤其是三阴性乳腺癌(ER-、PR-、HER2-野生型(Wt)；TNBC)。 在这里，金纳博士将研究ER/PR的一种高度侵袭性亚型--乳腺癌的生物学， 这对非洲血统的女性造成了不成比例的影响。四阴性乳腺癌 (ER-，PR-，HER2-wt，AR-；QNBC)现在已经超过TNBC成为最具侵略性的乳房 癌症亚型1。除了缺乏可操作的乳腺癌靶点表达外，ER， 在TNBC中，QNBCs也缺乏可作用的雄激素受体(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， 这是造成乳腺癌总体种族负担不同的原因之一。因此，替代方案 迫切需要QNBC中的可操作靶点来应对这一新的临床挑战。在我的 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Kinesin家族成员C1(KIFC1)在 QNBCs(与TNBC相比)。这项提案的目标是调查KIFC1是攻击性的驱动因素 QNBC生物学和QNBC患者的潜在治疗靶点。在这里，珍娜博士将确定 在Mark La博士开发的临床前模型中，AR-Loss如何促进侵略性QNBC生物学 为未来的治疗干预进行驳船。

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.