Research

Cell cycle entry is a fundamental process that is integral to development and tissue maintenance. When this process becomes dysregulated, it often leads to the development of cancer. Our laboratory is dedicated to unraveling the signaling mechanisms that govern the decision to proliferate in both normal and cancer cells. In particular, we seek to understand how cancer cells evolve and develop resistance to targeted therapies.

Beyond the conventional understanding of drug-resistance mutations, recent research has uncovered non-genetic mechanisms in certain subsets of cancer cells that can rapidly adapt to targeted therapies. This adaptation results in the formation of drug-tolerant persister cells (persisters). Not only do these persisters drive residual cancer growth, but they also serve as a breeding ground for the evolution of resistance mutations. Our recent study on BRAF-mutant melanoma (Kim et al., 2023, Cell Rep) has shed light on how heterogeneity in RTK signaling contributes to the development of BRAF/MEK inhibitor tolerance, eventually leading to drug resistance.

We are also keen on exploring new research directions that align with our interests. In our quest to comprehend the intricacies of these processes, we utilize integrated approaches that encompass single-cell live imaging, RNA sequencing, and metabolomic analysis. Ultimately, our goal is to leverage insights from these mechanistic studies to develop novel, precision-targeted therapies for human diseases. By doing so, we hope to significantly improve patient outcomes and redefine the landscape of cancer treatment.

Signnificant cell-to-cell variability in ERK signaling.