Cell Fate Engineering

Our research in Cell Fate Engineering is centered on a core question: how do we precisely control a cell’s identity and function for therapeutic and regenerative applications? To answer this, we focus on the intricate interplay between a cell’s transcriptional state and its physical environment. Our lab is pioneering strategies to steer cell fate with high fidelity, aiming to overcome critical hurdles in regenerative medicine and disease modeling.

Our Approach: We use an integrative approach that combines advanced biological techniques with quantitative analysis to understand and manipulate the mechanisms that dictate a cell’s destiny. Our work in this area is currently focused on:

Engineering Reprogramming Efficiency and Genomic Stability: We have identified that the adhesome, a collection of proteins mediating cell-matrix and cell-cell adhesions, may act as a barrier to successful reprogramming. Our research aims to improve the generation of induced pluripotent stem cells (iPSCs) by disrupting specific adhesome genes to enhance reprogramming efficiency. 

Manipulating Adhesome Signaling in Disease: Beyond reprogramming, we investigate how the adhesome acts as a regulatory hub for cell fate transitions in diseases like cancer. We have found that disrupting adhesome genes can facilitate the acquisition of cancer stem cell (CSC)-like traits in lung cancer cells. This disruption can rewire cell fate trajectories, leading to increased metastatic potential and a greater tumor burden in mouse models.

Decoding Developmental Trajectories: Using advanced techniques like single-cell RNA-sequencing, we are able to map the developmental trajectories of cells in real-time. For instance, we have shown that downregulating adhesome genes can direct reprogramming along a more favorable reprogramming trajectory, as opposed to alternative, less efficient routes. This work also explores how the loss of adhesome components can modulate transcriptional noise and alter cell-cell communication networks, revealing new ways to control cell fate transitions.