Aileen W. Li, Ph.D., CRI-Merck Fellow University of California, San Francisco

To communicate with each other, our immune cells use a number of different molecules—cytokines, chemokines, and growth factors—that can influence movement, activity, and a variety of other behaviors. However, the precise role of some of these immune signaling molecules and their relationships with each other, especially within the context of tumors, remains unclear. Therefore, Dr. Li aims to use a new technology involving artificial “synNotch” receptors to control the immune-related signaling within the tumor microenvironment and systemically characterize how these molecules individually impact tumor growth.

With this technology, which was developed by her sponsor, Li is creating specialized “helper” T cells that can be designed to recognize specific tumor antigens and then turn on specific genes and produce defined molecules in response. By increasing or decreasing the production of various molecules, Li seeks to uncover insights into which ones help tumors grow and which promote their elimination, and furthermore, how such factors interact with each other (synergy, redundancy, cooperativity) to shape the tumor ecosystem. Ultimately, Li hopes that these insights will enable superior T cells to be engineered as well as can be combined more effectively with existing immunotherapies.

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