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:

Physical organization and dynamics of the genome, Architecture of large protein complexes such as the centrosome, and

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:

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 New fluorescent probes based on fluorescent proteins, nanobodies and aptamers so that biological questions can be converted into "imageable" ones.

Y. Wang, J. Schnitzbauer, Z. Hu, X. Li, Y. Cheng, Z.L. Huang, B. Huang, "Localization events-based sample drift correction for localization microscopy with redundant cross-correlation algorithm", Opt. Express, 22, 15982-15991 (2014) R. McGorty, J. Schnitzbauer, W. Zhang, B. Huang, "Correction of depth-dependent aberrations in 3D single molecule localization and super-resolution microscopy", Opt. Lett., 39, 275-278 (2014) B. Chen, L.A. Gilbert, B.A. Cimini, J. Schnitzbauer, W. Zhang, G.W. Li, J. Park. E.H. Blackburn, J.S. Weissman, L.S. Qi, B. Huang, "Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system", Cell, 155, 1479-1491(2013) E.M. Puchner, J.M. Walter, R. Kasper, B. Huang, W.A. Lim, "Counting molecules in single organelles with super-resolution microscopy Allows Tracking of the Endosome Maturation Trajectory", Proc. Nat. Acad. Soc. USA, 110, 16015-16020 (2013) J. Schnitzbauer, R. McGorty, B. Huang, "4Pi fluorescence detection and 3D particle localization with a single objective", Opt. Express 21, 19701-19708 (2013) F. Huang, X. Wang, E.M. Ostertag, T. Nuwal, B. Huang, Y.N. Jan, A.I. Basbaum and L.Y. Jan, "TMEM16C facilitates Na(+)-activated K(+) currents in rat sensory neurons and regulates pain processing", Nat. Neurosci., 16, 1284-1290 (2013) R. McGorty, D. Kamiyama, B. Huang, "Active microscope stabilization in three dimensions using image correlation", Optical Nanoscopy, 2, 3 (2013) R. Irannejad, J.C. Tomshine, J.R. Tomshine, M. Chevalier, J. Steyaert, S.G.F. Rasmussen, H. El-Samad, B. Huang, M. von Zastrow, "Conformational biosensors reveal adrenoceptor signaling from endosomes", Nature, 495, 534-538 (2013) V. Mennella, B. Keszthelyi, K.L. McDonald, B. Chhun, F. Kan, G.C. Rogers, B. Huang, D.A. Agard, "Sub-diffraction-resolution fluorescence microscopy reveals a novel domain of the centrosome critical for pericentriolar material organization", Nat. Cell Biol, 14, 1159-1168 (2012) L. Zhu, W. Zhang, D. Elnatan, B. Huang, "Faster STORM using compressed sensing", Nat Methods, 9, 721-723 (2012) G.M.J. Beaudoin, III, G.M. Schofield, T. Nuwal, K. Zang, E.M. Ullian, B. Huang, L.F. Reichard, "Afadin, a Ras/Rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus", J Neurosci., 32, 99-110 (2012)