Decoding and rewiring biochemical sensing to design spatially targeted cell therapies and drug delivery – turning the tumor’s signals against it

Evolution generated natural ‘immunity’ mechanisms that prevent and reverse pathological processes. These mechanisms provide the inspiration, the machinery, and the starting blueprint, but not the endpoint for how cancer can be prevented and cured. The overarching goal of my research is to better understand these beautifully dynamic mechanisms and their constraints and further evolve and engineer them for disease treatment and prevention. Using genetic and genomics tools guided by directed evolution and rational design, we reconfigure immunity across scales, from generating new proteins and receptors to cell functions and coordinated responses at the whole-body level. This allows us to discover and design programmable mechanisms fundamentally different from those previously identified, implement these as increasingly more effective therapeutic interventions, and, hopefully, contribute to a future where cancer, in all its forms, will be a curable and preventable disease.

Dr. Jerby is an Assistant Professor of Genetics at Stanford University. She studies the self-organizing and dynamic nature of cellular responses to uncover and design new mechanisms that selectively eliminate cancer and other disease-promoting cells. To this end, her laboratory integrates functional genomics, synthetic biology, machine learning, and cell and protein engineering. Since joining Stanford in November 2020, her laboratory has uncovered metabolite-based mechanisms to redirect immune cells to solid tumors; identified novel regulators and RNA-based interventions for immune-based elimination of cancer and virally infected cells; developed new tools to track the impact of genetic perturbations in intact tissue; and mapped tumor organization at unprecedented scales, opening new basic and translational research directions the laboratory is actively pursuing. Dr. Jerby holds a BSc, MSc, and PhD in Life and Computer Sciences from Tel Aviv University and completed her postdoctoral training in Dr. Aviv Regev’s laboratory at the Broad Institute of MIT and Harvard. She is the recipient of numerous awards, including the Chan Zuckerberg Biohub Investigator Award, the Paul G. Allen Distinguished Investigator Award, the Ovarian Cancer Research Alliance Liz Tilberis Early Career Award, and the Burroughs Wellcome Fund Career Award at the Scientific Interface.

Cell immunotherapies can be very effective but remain limited against solid tumors, in part because not enough immune cells reach the tumor. We recently discovered new ways to mobilize immune cells to solid tumors using a unique set of metabolite-sensing receptors. Once engineered to express these receptors, immune cells detect and follow metabolites released by tumors like scent trails and become significantly more effective at eradicating aggressive tumors. Yet, we are only beginning to understand these mechanisms and how to use them. With the support of the Pershing Foundation, we will study and reconfigure these receptors to control immune cell location and function. Using genetic tools, AI, and structural biology, we will identify the optimal sensors to mobilize immune cells to different types of solid tumors, learn their activity patterns across the body, and structure-function “rules”. We will design and introduce synthetic sensors and circuits to guide immune cells to the tumor, activate their killing capabilities only once inside it, and equip them to deliver therapeutic proteins and RNA molecules that we have recently found to dismantle tumors’ defenses. This research will allow us to turn the tumor’s chemical signals into immune guidance and control cues, opening avenues for the development of spatially targeted cell therapies.

"The Prize will allow us to build on our recent discoveries and establish systems to read and write the code of bioactive molecule sensing. Using these systems, we will design self-directed and context-dependent cell behaviors to lay the groundwork for a new class of cell therapies."