Research Interests
From single cells to human health, we make the invisible visible. By developing spatial multiomics and super-resolution microscopy, we create tools to identify new biomarkers and watch their interactions in organelles, cells, tissues, and humans, unlocking the secrets of life and disease to find new cures.
1 minute about Shi Lab
I. How cellular machineries are organized at the molecular scale?
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 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: Label-Retention Expansion Microscopy (LR-ExM), Landscape Expansion Microscopy (land-ExM), Nanomaterials, Live-cell single-particle tracking, Stochastic Optical Reconstruction Microscopy (STORM), Structured Illumination Microscopy (SIM), Airyscan Microscopy
II. How single-cell multiomic data are organized at the spatial scale?
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 a 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 of how cell phenotypes are maintained in native tissue and become perturbed in disease.
III. New and better biomarkers for diagnosis and precision medicine
We are dedicated to discovering new and better biomarkers to advance diagnosis and precision medicine related to aging, including Alzheimer's disease, schizophrenia, depression, and solid tumors. By employing unbiased discovery methods developed in our lab, such as spatial proteomics, spatial multiomics, super-resolution imaging, and nanomaterial interfaces, we aim to identify novel biomarkers that directly lead to improved diagnostic tools and more effective, personalized precision medicine strategies.
Research Funds
NIH Director's New Innovator Award (DP2)
NIH Pathway to Independence Award (K99/R00)
Hellman Fellow
Chan Zuckerberg Initiative Visual Proteomics Imaging Award
Chan Zuckerberg Initiative Advancing Imaging Through Collaborative Projects
Mary Anne Koda-Kimble Seed Award
Center of Cancer Systems Biology Pilot Grant
UC Irvine start-up fund
