Wilson Wong

Our ability to observe biological systems has advanced dramatically over the past decades. However, our ability to modulate and control biology, especially through genetic means, has been lagging.  Even with the recent developments in genome editing, we cannot still dynamically regulate cell functions, especially in complex living multicellular organisms such as mammals, with independent control of multiple processes and cell types simultaneously. This deficiency has hindered our ability to recapitulate and investigate complex natural multicellular processes. It also limits our ability to develop safe and effective therapies.

The overarching goal of my lab for the past decade has been to develop ways to control mammalian cell functions through engineering, biological network design, molecular biology, and chemical biology for medical applications, such as CAR T cell therapy. Our work can be broadly characterized into four different levels of regulation: receptor signaling, post-transcription, transcription, and DNA. Receptor engineering allows us to control how cells communicate with each other, either through cell surface or soluble ligands. Transcription and post-transcription regulation enable us to program the transcriptome by modulating coding and non-coding RNAs. DNA level control allows us to perform ultra-complex cellular computations that approach the complexity and sophistication found in natural systems. We developed orthogonal systems at each level, allowing us to regulate multiple genes and signaling independently. Our systems can be either regulated by FDA-approved drugs or light, and they are extensively optimized for robustness. To determine their clinical potential, we evaluated their performance in mice and/or in primary human immune cells. Together, our collection affords us unprecedented control over mammalian cell function.