The King Laboratory aims to leverage our expertise in cell mechanobiology, biotransport phenomena, and targeted drug delivery to reveal new insights into the physical and molecular mechanisms of metastatic cancer and translate these concepts to the clinic. Goal1: Elucidate the Mechanobiology of Cancer Cell Aggregates at the Blood Interface. Mechanotransduction of cancer cells in solid tumors is an active area of research, yet far less has been done to understand the response of cancer cells to fluid forces in blood flow. We have demonstrated the synergistic effect of shear stress and TRAIL on cellular apoptosis of circulating tumor cells (CTCs), as well as the unique ability of cancer cells ...

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The King Laboratory aims to leverage our expertise in cell mechanobiology, biotransport phenomena, and targeted drug delivery to reveal new insights into the physical and molecular mechanisms of metastatic cancer and translate these concepts to the clinic. Goal1: Elucidate the Mechanobiology of Cancer Cell Aggregates at the Blood Interface. Mechanotransduction of cancer cells in solid tumors is an active area of research, yet far less has been done to understand the response of cancer cells to fluid forces in blood flow. We have demonstrated the synergistic effect of shear stress and TRAIL on cellular apoptosis of circulating tumor cells (CTCs), as well as the unique ability of cancer cells to survive extremely high pulses of shear stress, similar to blood cells. Given that the presence of CTC aggregates in the blood signal more aggressive and metastatic disease, tissue engineered aggregates modeled after aggregates isolated and characterized from colorectal cancer patient blood samples will be tested in vitro for their stability and biological responses, and also injected into an experimental mouse model of bloodborne metastasis. Goal2: Develop a Mechanobiology Approach to CAR-T Therapy Applied to Metastatic Prostate Cancer. With the clinical success of cancer chimeric antigen receptor (CAR) T cell immunotherapy for blood cancers, there remain significant challenges for treating solid tumors. A major challenge in current T cell immunotherapies involves low cytotoxicity and persistence at the tumor site, which can be attributed to incomplete ex vivo T cell activation prior to reinfusion. Recent studies have shown significantly increased T cell activation through stimulation of the mechanosensitive ion channel Piezo1. We hypothesize that the ex vivo activation of T cells through exposure to fluid shear stress will significantly enhance activation levels, leading to increased transduction efficiency, cytotoxicity, and persistence of CAR T cells to treat solid tumors.

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