Seeing is believing. A major objective of our research program is to directly visualize how cells organize proteins, RNA, and DNA in space and time. We have developed a series of super-resolution microscopy methods to dissect the architecture of cellular structures at the molecular resolution, and with high labeling efficiency, brightness, and detection sensitivity. We are particularly interested in the structure-function relationships of the nuclear lamina, chromatin, cytoplasmic vesicles, and cellular protrusions called cilia. 

Methods: Expansion Microscopy (ExM), Stochastic Optical Reconstruction Microscopy (STORM), Structured Illumination Microscopy (SIM), Airyscan Microscopy

Hedgehog signaling pathway is the key signaling regulator of embryonic tissue patterning and adult tissue homeostasis. Defects in Hedgehog signaling can cause a multitude of developmental diseases, such as a congenital heart disease, and cancers, such as melanoma. Primary cilia, specialized protrusions on cell membrane, have an essential role in Hedgehog signaling in mammals. Our research objective is to determine the molecular mechanisms that underlie the regulation of Hedgehog signaling by primary cilia. Empowered by fast imaging and endogenous labeling technologies, we are able to directly watch and analyze the behavior of signaling and transporter molecules in action.

Methods: Live-cell single-particle tracking, Light-sheet microscopy, Total Internal Reflection Fluorescence Microscopy (TIRF), photoconversion

Over the last few years we are witnessing rapid advances in the fields of single-cell transcriptomics, genomics and proteomics. However, most tissues and organs are solid, with cells encased within a complex extracellular matrix network. Studying single cells from solid tissues usually requires their mechanical and enzymatic disaggregation. As a result, the positional information is lost, which is otherwise essential for proper understanding of how cells cooperate in tissues. We take optical and chemical approaches to develop novel, spatially-resolved multiomic methods, which isolate cells without homogenization, enable cell phenotyping with super resolution, and allow multiomics in the same single cells. This novel platform will significantly advance our knowledge on how cell phenotypes are maintained in native tissue and become perturbed in disease.