Zhe J. Liu
Hunterian 613
Research Interests
We combine quantitative imaging, genomic, and genetic approaches to uncover mechanisms of gene regulation across scales. Our work measures transcription-factor dynamics and molecular interactions in living cells, maps the three-dimensional organization of the genome at nanoscale resolution, and profiles RNA, proteins, and cellular architecture in intact tissues. By integrating these measurements with genetic and chemical perturbations, we seek to determine how molecular dynamics and genome organization shape coordinated gene expression, cell state, and tissue function.
When existing methods cannot resolve the biological questions in front of us, we build the necessary technologies. Our lab develops custom microscopes, molecular probes and imaging chemistries, automated fluidics and experimental systems, and computational methods for large-scale imaging and genomic data. We emphasize single-cell measurements with low noise, high dynamic range, high multiplexing, and high throughput. By combining precise measurement with systematic perturbation, we aim to create generalizable platforms for causal and predictive studies of gene regulation, cell state, and tissue physiology across development, aging, and disease.
Selected Publications
Gandin V, Kim J, Yang L, Lian Y, Kawase T, Hu A, Rokicki K, Fleishman G, Tillberg P, Castrejon AA, Stringer C, Preibisch S, Liu ZJ (2025) Deep-tissue transcriptomics and subcellular imaging at high spatial resolution. Science, 388(6744):eadq2084.
Dong P, Zhang S, Gandin V, Xie L, Wang L, Lemire AL, Li W, Otsuna H, Kawase T, Lander AD, Chang HY, Liu ZJ(2024) Cohesin prevents cross-domain gene co-activation. Nature Genetics, 56(8):1654-1664.
Xie L, Dong P, Qi Y, Hsieh TS, English B, Jung S, Chen X, Marzio MD, Chen X, Casellas R, Chang HY, Zhang B, Tjian R, Liu Z (2022) BRD2 compartmentalizes the accessible genome. Nature Genetics, 54(4):481-491.
Xie L, Dong P, Qi Y, Marzio MD, Chen X, Banala S, Legant WR, English B, Hansen A, Schulmann A, Lavis LD, Betzig E, Chang HY, Zhang B, Tjian R, Liu Z (2020) 3D ATAC-PALM: super-resolution imaging of the accessible genome. Nature Methods, 17(4):430-436.
Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, Pasolli HA, Xu S, Pang S, Hess HF, Lippincott-Schwartz J, Liu Z (2019) Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell, 177(6):1522-1535.
Liu H, Dong P, Ioannou MS, Shea J, Pasolli A, Grimm JB, Rivlin P, Lavis LD, Koyama M, Liu Z (2018) Visualizing long-term single-molecule dynamics in vivo by stochastic protein labeling. Proc Natl Acad Sci U S A, 115(2):343-348.
Chen J, Zhang Z, Li L, Chen B, Revyakin A, Hajj B, Legant W, Dahan M, Lionnet T, Betzig E, Tjian R, Liu Z (2014) Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell, 156(6):1274-1285.