Bo Huang, PhD

Professor
Pharmaceutical Chemistry
+1 415 476-1866

Cellular processes are carried out by coordinated participation of many biomolecules in a tiny volume. Many people have been dreaming to see clear pictures of these processes in order to understand how these molecules work together. Taking on this challenge, we are developing new visualization techniques and imaging probes by combining super-resolution microscopy, protein engineering and microfluidic automation. We are particularly interested in the following problems:

(1) Physical organization and dynamics of the genome,
(2) Architecture of large protein complexes such as the centrosome, and
(3) Spatial distribution of membrane proteins, particularly G-protein coupled receptors and neuron adhesion molecules, and how this distribution defines their signaling specificity.

In order to study these systems, we are developing the following microscopy technologies:

(1) Super-resolution and light-sheet microscopes that can visualize subcellular structures at a higher spatial resolution, record long term cell behavior, and track cells in intact animals, and
(2) New fluorescent probes based on fluorescent proteins, nanobodies and aptamers so that biological questions can be converted into "imageable" ones.

Research Summary: 
Understanding the spatial organization of cell signaling molecules and nuclear genome in development and cancer using microscopy and protein/cell engineering.
Publications: 

HybriSeq: Probe-based Device-free Single-cell RNA Profiling.

bioRxiv : the preprint server for biology

Foyt D, Brown D, Zhou S, Huang B

YAP charge patterning mediates signal integration through transcriptional co-condensates.

bioRxiv : the preprint server for biology

Meyer K, Yserentant K, Cheloor-Kovilakam R, Ruff KM, Chung CI, Shu X, Huang B, Weiner OD

Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.

Nature communications

Haderk F, Chou YT, Cech L, Fernández-Méndez C, Yu J, Olivas V, Meraz IM, Barbosa Rabago D, Kerr DL, Gomez C, Allegakoen DV, Guan J, Shah KN, Herrington KA, Gbenedio OM, Nanjo S, Majidi M, Tamaki W, Pourmoghadam YK, Rotow JK, McCoach CE, Riess JW, Gutkind JS, Tang TT, Post L, Huang B, Santisteban P, Goodarzi H, Bandyopadhyay S, Kuo CJ, Roose JP, Wu W, Blakely CM, Roth JA, Bivona TG

CELL-E 2: Translating Proteins to Pictures and Back with a Bidirectional Text-to-Image Transformer.

Advances in neural information processing systems

Khwaja E, Song YS, Agarunov A, Huang B

Efficient tagging of endogenous proteins in human cell lines for structural studies by single-particle cryo-EM.

Proceedings of the National Academy of Sciences of the United States of America

Choi W, Wu H, Yserentant K, Huang B, Cheng Y

Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project.

Molecular cell

Dekker J, Alber F, Aufmkolk S, Beliveau BJ, Bruneau BG, Belmont AS, Bintu L, Boettiger A, Calandrelli R, Disteche CM, Gilbert DM, Gregor T, Hansen AS, Huang B, Huangfu D, Kalhor R, Leslie CS, Li W, Li Y, Ma J, Noble WS, Park PJ, Phillips-Cremins JE, Pollard KS, Rafelski SM, Ren B, Ruan Y, Shav-Tal Y, Shen Y, Shendure J, Shu X, Strambio-De-Castillia C, Vertii A, Zhang H, Zhong S

Structural insights into the human PA28-20S proteasome enabled by efficient tagging and purification of endogenous proteins.

Proceedings of the National Academy of Sciences of the United States of America

Zhao J, Makhija S, Zhou C, Zhang H, Wang Y, Muralidharan M, Huang B, Cheng Y

High activity and high functional connectivity are mutually exclusive in resting state zebrafish and human brains.

BMC biology

Zarei M, Xie D, Jiang F, Bagirov A, Huang B, Raj A, Nagarajan S, Guo S

In Vivo Dopamine Neuron Imaging-Based Small Molecule Screen Identifies Novel Neuroprotective Compounds and Targets.

Frontiers in pharmacology

Kim GJ, Mo H, Liu H, Okorie M, Chen S, Zheng J, Li H, Arkin M, Huang B, Guo S

OpenCell: Endogenous tagging for the cartography of human cellular organization.

Science (New York, N.Y.)

Cho NH, Cheveralls KC, Brunner AD, Kim K, Michaelis AC, Raghavan P, Kobayashi H, Savy L, Li JY, Canaj H, Kim JYS, Stewart EM, Gnann C, McCarthy F, Cabrera JP, Brunetti RM, Chhun BB, Dingle G, Hein MY, Huang B, Mehta SB, Weissman JS, Gómez-Sjöberg R, Itzhak DN, Royer LA, Mann M, Leonetti MD

Image denoising for fluorescence microscopy by supervised to self-supervised transfer learning

Optics express

Y. Wang, H. Pinkard, E. Khwaja, S. Zhou, L. Waller, B. Huang

A zebrafish screen reveals Renin-angiotensin system inhibitors as neuroprotective via mitochondrial restoration in dopamine neurons.

eLife

Kim GJ, Mo H, Liu H, Wu Z, Chen S, Zheng J, Zhao X, Nucum D, Shortland J, Peng L, Elepano M, Tang B, Olson S, Paras N, Li H, Renslo AR, Arkin MR, Huang B, Lu B, Sirota M, Guo S

A ciliopathy complex builds distal appendages to initiate ciliogenesis.

The Journal of cell biology

Kumar D, Rains A, Herranz-Pérez V, Lu Q, Shi X, Swaney DL, Stevenson E, Krogan NJ, Huang B, Westlake C, Garcia-Verdugo JM, Yoder BK, Reiter JF

Label-retention expansion microscopy.

The Journal of cell biology

Shi X, Li Q, Dai Z, Tran AA, Feng S, Ramirez AD, Lin Z, Wang X, Chow TT, Chen J, Kumar D, McColloch AR, Reiter JF, Huang EJ, Seiple IB, Huang B

Polarized endosome dynamics engage cytoplasmic Par-3 that recruits dynein during asymmetric cell division.

Science advances

Zhao X, Garcia JQ, Tong K, Chen X, Yang B, Li Q, Dai Z, Shi X, Seiple IB, Huang B, Guo S

Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules.

Cell

Tulpule A, Guan J, Neel DS, Allegakoen HR, Lin YP, Brown D, Chou YT, Heslin A, Chatterjee N, Perati S, Menon S, Nguyen TA, Debnath J, Ramirez AD, Shi X, Yang B, Feng S, Makhija S, Huang B, Bivona TG

Versatile Labeling and Detection of Endogenous Proteins Using Tag-Assisted Split Enzyme Complementation.

ACS chemical biology

Makhija S, Brown D, Rudlaff RM, Doh JK, Bourke S, Wang Y, Zhou S, Cheloor-Kovilakam R, Huang B

HP1 proteins compact DNA into mechanically and positionally stable phase separated domains.

eLife

Keenen MM, Brown D, Brennan LD, Renger R, Khoo H, Carlson CR, Huang B, Grill SW, Narlikar GJ, Redding S

Spatial decoding of endosomal cAMP signals by a metastable cytoplasmic PKA network.

Nature chemical biology

Peng GE, Pessino V, Huang B, von Zastrow M

Nanotopography Enhances Dynamic Remodeling of Tight Junction Proteins through Cytosolic Liquid Complexes.

ACS nano

Huang X, Shi X, Hansen ME, Setiady I, Nemeth CL, Celli A, Huang B, Mauro T, Koval M, Desai TA

Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency.

Nature

Zhang J, Velmeshev D, Hashimoto K, Huang YH, Hofmann JW, Shi X, Chen J, Leidal AM, Dishart JG, Cahill MK, Kelley KW, Liddelow SA, Seeley WW, Miller BL, Walther TC, Farese RV, Taylor JP, Ullian EM, Huang B, Debnath J, Wittmann T, Kriegstein AR, Huang EJ

A molecular mechanism for probabilistic bet hedging and its role in viral latency.

Proceedings of the National Academy of Sciences of the United States of America

Chaturvedi S, Klein J, Vardi N, Bolovan-Fritts C, Wolf M, Du K, Mlera L, Calvert M, Moorman NJ, Goodrum F, Huang B, Weinberger LS

Bright split red fluorescent proteins for the visualization of endogenous proteins and synapses.

Communications biology

Feng S, Varshney A, Coto Villa D, Modavi C, Kohler J, Farah F, Zhou S, Ali N, Müller JD, Van Hoven MK, Huang B

Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity.

eLife

Alexander JM, Guan J, Li B, Maliskova L, Song M, Shen Y, Huang B, Lomvardas S, Weiner OD

Epi-illumination SPIM for volumetric imaging with high spatial-temporal resolution.

Nature methods

Yang B, Chen X, Wang Y, Feng S, Pessino V, Stuurman N, Cho NH, Cheng KW, Lord SJ, Xu L, Xie D, Mullins RD, Leonetti MD, Huang B

The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research.

Cell

Das S, Extracellular RNA Communication Consortium, Ansel KM, Bitzer M, Breakefield XO, Charest A, Galas DJ, Gerstein MB, Gupta M, Milosavljevic A, McManus MT, Patel T, Raffai RL, Rozowsky J, Roth ME, Saugstad JA, Van Keuren-Jensen K, Weaver AM, Laurent LC

Deformed alignment of super-resolution images for semi-flexible structures.

PloS one

Shi X, Garcia G, Wang Y, Reiter JF, Huang B

Multicolor fluorescent imaging by space-constrained computational spectral imaging.

Optics express

Wang Y, Yang B, Feng S, Pessino V, Huang B

Efficient labeling and imaging of protein-coding genes in living cells using CRISPR-Tag.

Nature communications

Chen B, Zou W, Xu H, Liang Y, Huang B

Local enrichment of HP1alpha at telomeres alters their structure and regulation of telomere protection.

Nature communications

Chow TT, Shi X, Wei JH, Guan J, Stadler G, Huang B, Blackburn EH

A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.

Cell

Percharde M, Lin CJ, Yin Y, Guan J, Peixoto GA, Bulut-Karslioglu A, Biechele S, Huang B, Shen X, Ramalho-Santos M

Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts.

The Journal of cell biology

Kelliher MT, Yue Y, Ng A, Kamiyama D, Huang B, Verhey KJ, Wildonger J

Co-translational protein targeting facilitates centrosomal recruitment of PCNT during centrosome maturation in vertebrates.

eLife

Sepulveda G, Antkowiak M, Brust-Mascher I, Mahe K, Ou T, Castro NM, Christensen LN, Cheung L, Jiang X, Yoon D, Huang B, Jao LE

Correlation analysis framework for localization-based superresolution microscopy.

Proceedings of the National Academy of Sciences of the United States of America

Schnitzbauer J, Wang Y, Zhao S, Bakalar M, Nuwal T, Chen B, Huang B

2-Hydroxyglutarate-Mediated Autophagy of the Endoplasmic Reticulum Leads to an Unusual Downregulation of Phospholipid Biosynthesis in Mutant IDH1 Gliomas.

Cancer research

Viswanath P, Radoul M, Izquierdo-Garcia JL, Ong WQ, Luchman HA, Cairncross JG, Huang B, Pieper RO, Phillips JJ, Ronen SM

The centrosomin CM2 domain is a multi-functional binding domain with distinct cell cycle roles.

PloS one

Citron YR, Fagerstrom CJ, Keszthelyi B, Huang B, Rusan NM, Kelly MJS, Agard DA

Improved split fluorescent proteins for endogenous protein labeling.

Nature communications

Feng S, Sekine S, Pessino V, Li H, Leonetti MD, Huang B

Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome.

Nature cell biology

Shi X, Garcia G, Van De Weghe JC, McGorty R, Pazour GJ, Doherty D, Huang B, Reiter JF

Covalent Protein Labeling by SpyTag-SpyCatcher in Fixed Cells for Super-Resolution Microscopy.

Chembiochem : a European journal of chemical biology

Pessino V, Citron YR, Feng S, Huang B

Functional selectivity of GPCR-directed drug action through location bias.

Nature chemical biology

Irannejad R, Pessino V, Mika D, Huang B, Wedegaertner PB, Conti M, von Zastrow M

EGF and NRG induce phosphorylation of HER3/ERBB3 by EGFR using distinct oligomeric mechanisms.

Proceedings of the National Academy of Sciences of the United States of America

van Lengerich B, Agnew C, Puchner EM, Huang B, Jura N

Live Cell Imaging of Endogenous mRNA Using RNA-Based Fluorescence "Turn-On" Probe.

ACS chemical biology

Ong WQ, Citron YR, Sekine S, Huang B

A microscopic view of the cell.

Molecular biology of the cell

Huang B

A High-Content Larval Zebrafish Brain Imaging Method for Small Molecule Drug Discovery.

PloS one

Liu H, Chen S, Huang K, Kim J, Mo H, Iovine R, Gendre J, Pascal P, Li Q, Sun Y, Dong Z, Arkin M, Guo S, Huang B

A scalable strategy for high-throughput GFP tagging of endogenous human proteins.

Proceedings of the National Academy of Sciences of the United States of America

Leonetti MD, Sekine S, Kamiyama D, Weissman JS, Huang B

Imaging Specific Genomic DNA in Living Cells.

Annual review of biophysics

Chen B, Guan J, Huang B

Versatile protein tagging in cells with split fluorescent protein.

Nature communications

Kamiyama D, Sekine S, Barsi-Rhyne B, Hu J, Chen B, Gilbert LA, Ishikawa H, Leonetti MD, Marshall WF, Weissman JS, Huang B

Force Feedback Controls Motor Activity and Mechanical Properties of Self-Assembling Branched Actin Networks.

Cell

Bieling P, Li TD, Weichsel J, McGorty R, Jreij P, Huang B, Fletcher DA, Mullins RD

Expanding the CRISPR imaging toolset with Staphylococcus aureus Cas9 for simultaneous imaging of multiple genomic loci.

Nucleic acids research

Chen B, Hu J, Almeida R, Liu H, Balakrishnan S, Covill-Cooke C, Lim WA, Huang B

Specification of Dendritogenesis Site in Drosophila aCC Motoneuron by Membrane Enrichment of Pak1 through Dscam1.

Developmental cell

Kamiyama D, McGorty R, Kamiyama R, Kim MD, Chiba A, Huang B

Heavy water: a simple solution to increasing the brightness of fluorescent proteins in super-resolution imaging.

Chemical communications (Cambridge, England)

Ong WQ, Citron YR, Schnitzbauer J, Kamiyama D, Huang B

Biogenesis, delivery, and function of extracellular RNA.

Journal of extracellular vesicles

Patton JG, Franklin JL, Weaver AM, Vickers K, Zhang B, Coffey RJ, Ansel KM, Blelloch R, Goga A, Huang B, L'Etoille N, Raffai RL, Lai CP, Krichevsky AM, Mateescu B, Greiner VJ, Hunter C, Voinnet O, McManus MT

Open-top selective plane illumination microscope for conventionally mounted specimens.

Optics express

McGorty R, Liu H, Kamiyama D, Dong Z, Guo S, Huang B

Single molecule techniques--applications in biology.

FEBS letters

Puchner EM, Huang B, Gaub HE

Surface-chemistry effect on cellular response of luminescent plasmonic silver nanoparticles.

Bioconjugate chemistry

Sun S, Zhou C, Chen S, Liu J, Yu J, Chilek J, Zhao L, Yu M, Vinluan R, Huang B, Zheng J

Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system.

Cell

Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, Li GW, Park J, Blackburn EH, Weissman JS, Qi LS, Huang B

Amorphous no more: subdiffraction view of the pericentriolar material architecture.

Trends in cell biology

Mennella V, Agard DA, Huang B, Pelletier L

Counting molecules in single organelles with superresolution microscopy allows tracking of the endosome maturation trajectory.

Proceedings of the National Academy of Sciences of the United States of America

Puchner EM, Walter JM, Kasper R, Huang B, Lim WA

TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and regulates pain processing.

Nature neuroscience

Huang F, Wang X, Ostertag EM, Nuwal T, Huang B, Jan YN, Basbaum AI, Jan LY

Conformational biosensors reveal GPCR signalling from endosomes.

Nature

Irannejad R, Tomshine JC, Tomshine JR, Chevalier M, Mahoney JP, Steyaert J, Rasmussen SG, Sunahara RK, El-Samad H, Huang B, von Zastrow M

Single cell optical imaging and spectroscopy.

Chemical reviews

Stender AS, Marchuk K, Liu C, Sander S, Meyer MW, Smith EA, Neupane B, Wang G, Li J, Cheng JX, Huang B, Fang N

Development in the STORM.

Developmental cell

Kamiyama D, Huang B

Subdiffraction-resolution fluorescence microscopy reveals a domain of the centrosome critical for pericentriolar material organization.

Nature cell biology

Mennella V, Keszthelyi B, McDonald KL, Chhun B, Kan F, Rogers GC, Huang B, Agard DA

Super-resolution fluorescence imaging of organelles in live cells with photoswitchable membrane probes.

Proceedings of the National Academy of Sciences of the United States of America

Shim SH, Xia C, Zhong G, Babcock HP, Vaughan JC, Huang B, Wang X, Xu C, Bi GQ, Zhuang X

Faster STORM using compressed sensing.

Nature methods

Zhu L, Zhang W, Elnatan D, Huang B

Afadin, a Ras/Rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Beaudoin GM, Schofield CM, Nuwal T, Zang K, Ullian EM, Huang B, Reichardt LF

SnapShot: Light microscopy.

Cell

Kasper R, Huang B

An in-depth view.

Nature methods

Huang B

Superresolution imaging of chemical synapses in the brain.

Neuron

Dani A, Huang B, Bergan J, Dulac C, Zhuang X

Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system.

Nature cell biology

Wu M, Huang B, Graham M, Raimondi A, Heuser JE, Zhuang X, De Camilli P

New resolving power for light microscopy: applications to neurobiology.

Current opinion in neurobiology

Dani A, Huang B

Super-resolution optical microscopy: multiple choices.

Current opinion in chemical biology

Huang B

Super-resolution fluorescence microscopy.

Annual review of biochemistry

Huang B, Bates M, Zhuang X

Super-resolution microscopy by nanoscale localization of photo-switchable fluorescent probes.

Current opinion in chemical biology

Bates M, Huang B, Zhuang X

Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy.

Science (New York, N.Y.)

Huang B, Wang W, Bates M, Zhuang X

Multicolor super-resolution imaging with photo-switchable fluorescent probes.

Science (New York, N.Y.)

Bates M, Huang B, Dempsey GT, Zhuang X

A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein.

Proceedings of the National Academy of Sciences of the United States of America

Whorton MR, Bokoch MP, Rasmussen SG, Huang B, Zare RN, Kobilka B, Sunahara RK

Counting low-copy number proteins in a single cell.

Science (New York, N.Y.)

Huang B, Wu H, Bhaya D, Grossman A, Granier S, Kobilka BK, Zare RN

Generation of complex, static solution gradients in microfluidic channels.

Journal of the American Chemical Society

Wu H, Huang B, Zare RN

Phospholipid biotinylation of polydimethylsiloxane (PDMS) for protein immobilization.

Lab on a chip

Huang B, Wu H, Kim S, Kobilka BK, Zare RN

Effect of bin time on the photon counting histogram for one-photon excitation.

Chemphyschem : a European journal of chemical physics and physical chemistry

Perroud TD, Huang B, Zare RN

Photon counting histogram: one-photon excitation.

Chemphyschem : a European journal of chemical physics and physical chemistry

Huang B, Perroud TD, Zare RN

Photon counting histogram for one-photon excitation.

Chemphyschem : a European journal of chemical physics and physical chemistry

Perroud TD, Huang B, Wallace MI, Zare RN

Analysis of biomolecular interactions using a miniaturized surface plasmon resonance sensor.

Analytical chemistry

Whelan RJ, Wohland T, Neumann L, Huang B, Kobilka BK, Zare RN

Fluorescence emission and absorption spectra of single Anabaena sp. strain PCC7120 cells.

Photochemistry and photobiology

Ying L, Huang X, Huang B, Xie J, Zhao J, Zhao XS