Our Research

Seeing is Believing

We’re working to develop tools to enable discovery-driven biology in tissues. We aim to comprehensively map molecular processes in healthy and diseased tissues.

Modern sequencing methods have brought many new insights into transcriptome-wide analysis, but crucially lose a native spatial context. Additionally, traditional fluorescent imaging methods only identify a few different molecules in one sample.

We developed seqFISH to identify tens of thousands of different molecules. We’re continually building on our ability to identify, quantify, and understand how cell environments drive cell function.

Our Lab

The rapid growth of in situ imaging from a few genes to nearly the whole transcriptome was made possible by our interdisciplinary team of scientists and engineers. We developed the new molecular, fluidic, optical, and computational tools that made seqFISH+ possible.



Cai Lab is founded



First paper showing multiplexed RNA detection in single cells with super-resolution microscopy



First demonstration of seqFISH



249 genes imaged in brain sections with seqFISH
MEMOIR lineage tracing with seqFISH
Cai Lab moves from Caltech Chemistry to Caltech Biology



10,212 genes identified in vitro with RNA SPOTs



10,421 genes visualized by intron seqFISH
Cai Lab officially joins Caltech Biology



10,000 mRNAs detected with RNA seqFISH+

Featured Collaborations 

Elowitz Lab


Biorxiv preprint (2020) “Imaging cell lineage with a synthetic digital recording system

Nature Biotechnology (2019) “In situ readout of DNA barcodes and single base edits facilitated by in vitro transcription

Nature (2016) “Synthetic recording and in situ readout of lineage information in single cells

Nature (2015) “Combinatorial gene regulation bymodulation of relative pulse timing

Molecular Cell (2014) “Dynamic heterogeneity and DNA methylation in embryonic stem cells

Rothenberg Lab


Cell Systems (2019) “Single-Cell Analysis Reveals Regulatory Gene Expression Dynamics Leading to Lineage Commitment in Early T Cell Development”

Anderson  Lab


Cell (2019) “Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior”

Guttman Lab


Cell (2018) “Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus”

Yuan Lab


Nature Biotechnology (2018) “Identification of spatially associated subpopulations by combining scRNAseq and sequential fluorescence in situ hybridization data”

Genome Biology (2017) “Challenges and emerging directions in single-cell analysis

Biorxiv preprint (2019) “Giotto, a toolbox for integrative analysis and visualization of spatial expression data

Gradinaru Lab


Cell (2014) “Single-Cell Phenotyping within Transparent Intact Tissue through Whole-Body Clearing”

Nature Protocols (2015) “Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping

Cairns Lab

University of Utah

Cell Research (2018) “The adult human testis transcriptional cell atlas”

Bronner Lab


Nature Communications (2017) “Identification of a neural crest stem cell niche by Spatial Genomic Analysis”

Trapnell Lab

University of Washington

A Spatially resolved molecular Atlas of Human Endothelium (NIH)

Schier Lab


Shendure Lab

University of Washington

Allen Discovery Center for Lineage Tracing