Detection of Emergent Mechanical Properties of Biologically Complex Cellular States

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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.