Devan Shah

Nature has evolved distribution of labor between different cell types to build versatile multicellular systems. Inspired by this division of labor, I have built a synthetic cellular system wherein sensing, response, and feedback control functions are modularly distributed amongst distinct cell populations. Together, these network architectures enable cell specialization by distribution of labor, allow amplification of low level or sparse input signals, and achieve homeostatic response control which are behaviors we have harnessed to build novel t cell-based cancer immunotherapies.

I have engineered multicellular systems with cellular cascades that use “sensor” and “responder” cells to coordinate responses for applications in cancer immunotherapy. These systems rely on designer orthogonal paracrine or juxtacrine signaling channels, enabling upstream cells to induce or repress specific genetic outputs in downstream cells. The system I have developed is capable of 1. Modular sensing of input signals and recruitment of diverse response functions, 2. Spatial control over activation, 3. Feedback regulation for fine-tuned response control, 4. Amplification of circuit responses. We use these capabilities to design cell-based circuits that can precisely integrate multiple cancer markers to identify and eliminate harmful cancer cells and achieve functionalities beyond the reach of current single-cell engineering approaches. My work demonstrates that by leveraging division of labor, multicellular systems can overcome the manufacturing and productivity constraints of conventional single-cell engineering while enabling novel functionalities essential for the next generation of cell-based cancer immunotherapies.