The Jan laboratory primarily focuses on the development of clinically suitable synthetic biology platforms in order to advance next-generation cellular immunotherapies. We contribute to these goals by harnessing elegant protein degradation cellular machinery that has evolved to control fast biologic transitions related to information flow and signal processing and have developed molecular switch technologies regulated by the FDA-approved drug lenalidomide as generalizable chemical biology tools and cell therapy controllers. We use genomics, synthetic biology, and biochemistry to build new technologies, explore design principles for adaptive, user-controllable immune cells, and investigate clinical settings to deploy smart cell therapies.

Reprogramming protein degradation: Molecular glue degraders are frontline anti-cancer agents and herald extraordinary promise for degrader drug development. The target-drug-E3 ligase ternary complexes enforced by small molecule degraders are our starting point for synthetic biology development. We are learning to chemically and genetically retarget protein degradation machinery in order to control immune cell programming in new and therapeutically impactful ways. By advancing clinically suitable tools composed of human proteins and FDA-approved small molecules, we envision a platform for direct clinical translation.

Expanding the design space of cellular immunotherapy: Cellular states of dysfunction undermine CAR T cell effectiveness and are a prominent mechanism of treatment failure that could in theory be overcome by tuning therapeutic cell self-renewal and differentiation. Yet there are few static, irreversible genetic modifications that can safely manipulate these core cell fate dynamics. We are leveraging user-controlled, synthetic biology approaches to hack the central cellular processes that determine therapeutic potential.