Danfeng Cai Lab

What do lava lamps and cells have in common? Why do cells sometimes light up like a lava lamp? The Cai Lab is interested in studying the mysterious liquid-like compartments in a cell, just like oil droplets in a lava lamp.

Termed "biomolecular condensates" or membrane-less organelles, these compartments perform important functions in the cell such as transcription, chromatin organization, and cellular stress response, and are intimately linked to cellular homeostasis and diseases such as neurodegeneration and cancer. However, how they form and function are very poorly understood.

The Cai Lab aims to tackle this important question, using advanced imaging and proteomics tools.

We are a diverse and interdisciplinary group of scientists who believe that curiosity-driven research can lead to ground-breaking discoveries. We embrace the frequent intellectual interactions and collaborations with physician scientists, engineers, and mathematicians at Johns Hopkins University and throughout the world.

YAP/TEAD signaling is essential for organismal development, cell proliferation, and cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes is incompletely understood. YAP forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors to activate downstream target genes. In bioRxiv, we report that endogenous YAP forms sub-micron scale condensates in response to Hippo pathway regulation and actin cytoskeletal tension. The transcription factor TEAD1 actively stabilizes YAP condensates, which also recruit BRD4, a coactivator that is enriched at active enhancers. Using single molecule tracking, we found that YAP condensates slowed YAP diffusion within condensate boundaries, a possible mechanism for promoting YAP target search. These results reveal that YAP condensate formation is a highly regulated process that is critical for YAP/TEAD target gene expression.