Metastasis causes 90% of the mortality associated with solid tumors, such as breast cancer. Cancer metastasis is a multi-step process of cancer cell migration from the primary tumor sites to the distant secondary tumor sites. However, the molecular mechanisms underlying metastasis remain poorly understood and no effective approaches are available to cure metastasis. The goals of the Liu laboratory are to control metastasis and eliminate the mortality associated with breast cancer and other types of cancer.

The identification of cancer stem cells (CSCs), a subpopulation of cancer cells with stem cell properties, has brought us a new perspective on cancer, including leukemia and solid tumors. CSCs are proposed to mediate cancer relapse and metastasis due to their resistance to conventional therapies. Dr. Liu’s previous work has demonstrated that breast cancer stem cells (BCSCs) are able to mediate spontaneous lung metastases in human-in-mouse xenograft models. Her work has identified that miR-30c is a direct target of GATA3 in regulating both invasion and chemo-resistance, through targeting TWF1 and VIM (Nat Commu 2013, BRCT 2013) (Figure 1). Nevertheless, complete understanding, efficient imaging, effective targeting, and strategic differentiation of CSCs are among the most challenging tasks in cancer treatment.

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Holiday lunch outing at Indian Garden

We have four ongoing interactive basic and translational research directions (Figure 2): (1) to understand cancer stem cells (CSCs) using cutting-edge single cell sequencing technology and functional studies; (2) to image CSCs (their dynamic behavior and interactions with immune cells and non-CSCs) during metastasis using bioluminescence imaging and intravital imaging systems; (3) to target CSCs with novel therapeutics delivered by nanoparticles; (4) to re-differentiate CSCs.

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Valery presenting her research at the 2019 Pharmacology Retreat