Connie An

The ability to engineer new functions into cells through the delivery of DNA and RNA has greatly expanded our ability to treat diseases. To do this, therapeutic cells are engineered to express receptors and signals. The most notable example is CAR T cell therapy, in which T cells are engineered to express a chimeric antigen receptor or CAR, enabling the T cell to sense and kill cancer cells. CAR T cells are also being engineered to express cytokines, protein signals that modulate the immune environment. CAR T cell therapy has had great success treating liquid tumors, but its application to solid tumors has been limited due to efficacy issues and off-target effects. My work seeks to boost the safety and efficacy of CAR T cell therapy by ensuring that therapeutic signals and receptors are expressed in the right dosage, at the right time, and in the right place. To do this, I am engineering dosage-controlled sense-and-respond circuits to modulate CAR and cytokine signaling. Furthermore, I am keeping clinical translation in mind by using humanized components in my engineering. Ultimately, I aim to enhance our ability to control the dosage, timing, and localization of cell therapies.