Ruixuan Gao

Living organisms are composed of structures spanning orders of magnitude in size, and are assembled from tens of thousands of, if not more, distinct molecular entities. Our group’s research centers on the molecular nature of biological structures and processes. We are interested in how basic molecular building blocks—such as proteins, lipids, and RNAs—assemble and interact with one another to achieve specific biological functions, or cause dysfunctions.

We develop chemical, physical, and biomolecular tools that map and track these molecular building blocks at their natural length scale and temporal resolution. Basing our approach on chemical synthesis and molecular biology, we apply state-of-the-art methods in light/electron microscopy, bioengineering, and computational sciences to a range of biological questions at the molecular scale.

Molecular Components and Chemical Compositions of Living Organisms

Biological structures in living organisms span multiple orders of magnitude in size—ranging from nanometers to centimeters. We use chemical and material tools to study the molecular components and chemical compositions of these structures. Specifically, we leverage rational design of macromolecular matrices, supramolecular assemblies, and chemical linkers/probes to selectively target, identify, and visualize molecular entities in cells and tissues. Additionally, we develop (bio)chemical probes to map and track chemical compositions and dynamics in biological systems.

 Microscopy and Bioimaging

Observing dynamic biological processes at the molecular scale requires an imaging modality that captures thousands of molecular targets or more at nanoscopic spatial resolution and sub-millisecond temporal resolution. Currently, no microscopy methods fulfill these criteria concurrently. We develop fluorescence microscopy methods that overcome such limitations, including super-resolution microscopy, light-sheet microscopy, and adaptive optical microscopy.

 Structure, Function, and Pathology

We seek to elucidate structures and processes central to biology and human health. For instance, our group is interested in the anatomy and (dys)function of the nervous system, such as ultrastructure of synapses, chemical profile of synaptic transmission, long-range neuronal connections, and pathological effects of misfolded proteins in neuropathological brains. We also apply proteomics and transcriptomics approach to map endogenous and exogenous molecular markers in, for example, cancerous and clinical specimens.

10. R. Gao†, C.-C. Yu†, L. Gao, K.D. Piatkevich, R.L. Neve, J.B. Munro, S. Upadhyayula, E.S. Boyden*, “A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy,” Nat. Nanotechnol. 16, 698-707 (2021). [Link] [bioRxiv],9. O.A. Shemesh†, C.-Y. Linghu†, K.D. Piatkevich†, D. Goodwin, O.T. Celiker, H.J. Gritton, M.F. Romano, R. Gao, C.-C. Yu, H.-A. Tseng, S. Bensussen, S. Narayan, C.-T. Yang, L. Freifeld, C. Siciliano, I. Gupta, J. Wang, N. Pak, Y.-G. Yoon, J.F.P. Ullmann, B. Guner-Ataman, H. Noamany, Z.R. Sheinkopf, W.-M. Park, S. Asano, A.E. Keating, J.S. Trimmer, J. Reimer, A. Tolias, M.F. Bear, K.M. Tye, X. Han, M.B. Ahrens, E.S. Boyden*, “Precision calcium imaging of dense neural populations via a cell-body-targeted calcium indicator,” Neuron 107, 1-17 (2020). [Link] [bioRxiv],8. R. Gao†, S.M. Asano†, S. Upadhyayula†, I. Pisarev, D.E. Milkie, T.-L. Liu, V. Singh, A. Graves, G.H. Huynh, Y. Zhao, J. Bogovic, J. Colonell, C.M. Ott, C. Zugates, S. Tappan, A. Rodriguez, K.R. Mosaliganti, S.G. Megason, J. Lippincott-Schwartz, A. Hantman, G.M. Rubin, T. Kirchhausen, S. Saalfeld, Y. Aso, E.S. Boyden*, E. Betzig*, “Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution,” Science 363, eaau8302 (2019). [Link] [Cover] [bioRxiv],7. D. Oran†, S.G. Rodriques†, R. Gao, S.M. Asano, M.A. Skylar-Scott, F. Chen, P.W. Tillberg, A.H. Marblestone*, E.S. Boyden*, “3-D nanofabrication by volumetric deposition and controlled shrinkage of patterned scaffolds,” Science 362, 1281-1285 (2018). [Link],6. S.M. Asano†, R. Gao†, A.T. Wassie†, P.W. Tillberg, F. Chen, E.S. Boyden*, “Expansion microscopy: Protocols for imaging proteins and RNA in cells and tissues,” Curr. Protoc. Cell Biol. 80, e56 (2018). [Link],5. L. Freifeld, I. Odstrcil, D. Forster, A. Ramires, J.A. Gagnon, O. Randlett, E. Costa, S.M. Asano, O. Celiker, R. Gao, D.A. Martin-Alarcon, P. Reginato, C. Dick, L. Chen, D.E. Schoppik, F. Engert, H. Baier, E.S. Boyden*, “Expansion microscopy of zebrafish for neuroscience and developmental biology studies,” PNAS, E10799–E10808 (2017). [Link],4. R. Gao†, S.M. Asano†, E.S. Boyden*, “Q&A: Expansion microscopy”, BMC Biology 15, 50 (2017). [Link],3. Y-S. No†, R. Gao†, M. Mankin, R. Day, H-G. Park, C.M. Lieber*, “Encoding active device elements at nanowire tips,” Nano Lett. 16, 4713–4719 (2016). [Link],2. Gao, S. Strehle, B. Tian, T. Cohen-Karni, P. Xie, X. Duan, Q. Qing, C.M. Lieber*, “Outside looking in: Nanotube transistor intracellular sensors,” Nano Lett. 12, 3329-3333 (2012). [Link],1. Duan, R. Gao, P. Xie, T. Cohen-Karni, Q. Qing, H-S. Choe, B. Tian, X. Jiang, C.M. Lieber*, “Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor,” Nat. Nanotechnol. 7, 174-179 (2012). [Link]

(†: equal contribution; *: corresponding)

Postdoctoral Associate, MIT/HHMI Janelia Research Campus, 2015-2020
Ph.D., Harvard University, 2015
B.S., UC Berkeley, 2009