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This event will be held virtually on zoom. Check your email for the link and passcode or contact ksas@seas.upenn.edu.
Systems biology approaches, including computational models, provide a framework to test biological hypotheses and optimize effective therapeutic strategies to treat human diseases. In this talk, I present recent work in modeling signaling in cancer-targeting immune cells, including CAR T cells at Natural Killer cells. Chimeric antigen receptors (CARs) are comprised of a variety of different activating domains and co-stimulatory domains that initiate signaling required for T cell activation. There is a lack of understanding of the mechanisms by which activation occurs. We apply mathematical modeling to investigate how CAR structure influences downstream T cell signaling and develop new hypotheses for the optimal design of CAR-engineered T cell systems. Natural Killer cells also provide a useful platform for targeting cancer cells. However, NK cells have been shown to exhibit reduced killing ability with prolonged stimulation by cancer cells. We use a combination of mechanistic model, optimal control theory and in silico synthetic biology to investigate strategies to enhance NK cell-mediated killing.