We are interested in using physical concepts and experimental techniques to study fundamental questions in molecular biology. The biological systems under study include helicases that unzip DNA, DNA recombination intermediate called Holliday junction and its associated enzymes, folding and catalysis of hairpin and VS ribozymes, DNA replication machinery, and chromatin remodeling complexes. Our main experimental tool is single-molecule fluorescence spectroscopy and microscopy, supported by nano-mechanical tools such as magnetic and optical tweezers.

We use modern molecular biology techniques to engineer the molecules with fluorescence tags and tether them to a bio-friendly surface. Then, we shine laser light on each molecule to watch it do its thing. A clever design of such experiments can yield new insights to fundamental biological problems . We also use computational tools extensively, not only to acquire and analyze data, but also to model the problems mathematically, to exploit the genomic databases, and to simulate the molecular motions and reactions.

Recent Publications or search pubmed for group publications
(reprints available upon request)

  • Pandey, M., S. Syed, I. Donmez, G. Patel, T. Ha and S. S. Patel, "Coordinating DNA replication by means of priming loop and differential synthesis rate", Nature , (2009)
  • Roy, R., A. G. Kozlov, T. M. Lohman and T. Ha, "SSB protein diffusion on single-stranded DNA stimulates RecA filament formation", Nature 461(7267), 1092-1097 (2009)
  • Okumus, B., S. Arslan, S. Fengler, S. Myong and T. Ha, "Single Molecule Nanocontainers Made Porous Using a Bacterial Toxin", J. Am. Chem. Soc. 131, 14844–14849 (2009)
  • Honda M, J. Park, R. A. Pugh, T. Ha and M. Spies, "Single-molecule analysis reveals differential effect of ssDNA-binding proteins on DNA translocation by XPD helicase", Molecular Cell 35, 694-703 (2009)
  • Jena P., P Shirude, B. Okumus, K. Laxmi-Reddy, F. Godde, I. Huc, S. Balasubramanian and Taekjip Ha, "G-Quadruplex DNA Bound by a Synthetic Ligand is Highly Dynamic", J. Am. Chem. Soc. 131, 12522–12523 (2009) ( pdf )
  • Diao J., T.Y. Yoon, Z. Su, Y. K. Shin and T. Ha, "C2AB: A Molecular Glue for Lipid Vesicles with a Negatively Charged Surface", Langmuir 25(13), 7177-7180 (2009) ( pdf )
  • Sorokina M., H. R. Koh, S. S. Patel and T. Ha, "Fluoresecent Lifetime Trajectories of a Single Fluorophore Reveal Reaction Intermediates During Transcription Initiation", J Am Chem Soc 131, 9630–9631 (2009) ( pdf )
  • Ha, T., "Photonics: How nanocrystals lost their blink", Nature 459 (7247), 649-650 (2009) ( pdf )
  • Yodh, J.G., B.C. Stevens, K. Radhakrishnan, P. Janscak and T. Ha, "BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation", EMBO 28(4), 405-416 (2009) ( pdf )
  • Cornish, P.V., D. N. Ermolenko, D.W. Staple, L. Hoang, R.P. Hickerson, H.F. Noller and T. Ha, "Following movement of the L1 stalk between three functional states in single ribosomes", PNAS 106(8), 2571-2576 (2009)
  • Myong, S., S. Cui, P. V. Cornish, A. Kirchhofer, M. U. Gack, J. U. Jung, K. P. Hopfner and T. Ha, "Cytosolic viral sensor RIG-I is a 5\' - triphosphate-dependent translocase on double-stranded RNA", Science 323(5917), 1070-1074 (2009)
  • Heller, D., H. Jin, B. Martinez, D. Patel, B. Miller, T.-K. Yeung, P. Jena, C. Hobartner, T. Ha, S. Silverman, M. Strano, "Multimodal optical sensing and analyte specificity using single-walled carbon nanotubes", Nature Nanotechnology 4(2), 114-120 (2009) ( pdf )
  • Ishitsuka, Y. and T. Ha, "DNA nanotechnology: a nanomachine goes live", Nat Nanotechnol. 4 (5), 281-282 (2009)



  • Rothenberg, E., J. M. Grimme, M. Spies and T. Ha, "Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes", PNAS 205 (51), 20274-20279 (2008) ( pdf )
  • Lin, Y., L.-J. Lin, P. Sriratana, K. Coleman, T.Ha, M. Spies and I. K. O. Cann, "Engineering of functional replication protein A homologs based on insights in evolution of oligonucleotide/oligosaccharide binding (OB) folds", J. Bacteriology 190(17), 5766-5780 (2008) ( pdf )
  • Iqbal, A., S. Arslan, B. Okumus, T. J. Wilson, G. Giraud, D. G. Norman, T. Ha and D. M.J. Lilley, "Orientation dependence in fluorescent energy transfer between Cy3 and Cy5 terminally attached to double-stranded nucleic acids", PNAS 105(32), 11176-11181 (2008) ( pdf )
  • Su, Z., Y. Ishitsuka, T. Ha and Y.K. Shin, "The SNARE complex from yeast is partially unstructured on the membrane", Structure 16, 1138-1146 (2008) ( pdf )
  • Yoon, T.Y., X. Lu, J. Diao, S. M. Lee, T. Ha and Y. K. Shin, "Complexin and Calcium stimulate SNARE-mediated membrane fusion", Nature Structural & Molecular Biology 15, 707-713 (2008) ( pdf )
  • Gack, M. U., A. Kirchhofer, Y. C. Shin, K. S. Inn, C. Liang, S. Cui, S. Myong, T. Ha, K. P. Hopfner and J. U. Jung, "Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated anti-viral signal transduction", Proc Natl Acad Sci, USA 105(43), 16743-16748 (2008) ( pdf )
  • Cornish, P. V., D. N. Ermolenko, H. F. Noller and T. Ha, "Spontaneous Intersubunit Rotation in Single Ribosomes", Molecular Cell 30, 578-588 (2008) ( pdf )
  • Tang, G. Q., R. Roy, T. Ha and S. S. Patel, "Transcription Initiation in a Single-Subunit RNA Polymerase Proceeds through DNA Scrunching and Rotation of the N-Terminal Subdomains", Molecular Cell 30, 567-577 (2008) ( pdf )
  • Rasnik, I., Y. J. Yeong, S. A. McKinney, V. Rajagopal, S. S. Patel and T. Ha., "Branch migration enzyme as a Brownian ratchet.", EMBO J. 27, 1727–1735 (2008) ( pdf )
  • Roy, R., S. Hohng and T. Ha., "A practical guide to single-molecule FRET.", Nat. Methods 5, 507-516 (2008) ( pdf )
  • Joo, C., H. Balci, Y. Ishitsuka, C. Buranachai, and T. Ha , "Advances in Single-Molecule Fluorescence Methods for Molecular Biology", Ann. Rev. of Biochemistry 77, 51-76 (2008) ( pdf )
  • Selvin, P.R. and T. Ha, Editors, "Single Molecule Techniques: A Laboratory Manual", Cold Spring Harbor Laboratory Press ISBN 978-087969775-4, 507 pp (2008)



  • Rothenberg, E., M.A. Trakselis, S.D. Bell and T. Ha, "MCM fork substrate specificity involves dynamic interaction with the 5' tail", J. Biol. Chem. 282, 34229-34234 (2007)

  • Kim, H.K., I. Rasnik, J. Liu, T. Ha and Y. Lu, "Dissecting metal ion-dependent folding and catalysis of a single DNAzyme", Nature Chemical Biology 3, 763-768 (2007)

  • Yu, J., T. Ha and K. Schulten, "How Directional Translocation is Regulated in a DNA Helicase Motor", Biophys. J. 23, 11-23 (2007)
  • Hohng, S., R. Zhou, M. K. Nahas, J. Yu, K. Schulten, D. M. J. Lilley and T. Ha, "Fluorescence-force spectroscopy maps two-dimensional reaction landscape of the Holliday junction", Science 318, 279-283 (2007) ( pdf )
  • Myong, S., M. M. Bruno, A. M. Pyle and T. Ha,, "Spring-loaded Mechanism of DNA Unwinding by HCV NS3 Helicase", Science 317, 513-516 (2007) ( pdf )
  • Wilson, T. J., M. Nahas, L. Araki, S. Harusawa, T. Ha, D. M. Lilley, "RNA Folding and the Origins of Catalytic Activity in the Hairpin Ribozyme", Blood Cells Mol. Dis. 38(1), 8-14 (2007) ( pdf )
  • Ha, T., "Need for Speed: Mechanical Regulation of a Replicative Helicase", Cell 129(7), 1249-1250 (2007) ( pdf )
  • Shirude, P.S., B. Okumus, L. Ying, T. Ha and S. Balasubramanian, "Single Molecule Conformational Analysis of G-Quadruplex Formation in the Promoter DNA Duplex of the Proto-Oncogene C-kit", JACS 129(2), 7484-7485 (2007) ( pdf )
  • Cisse, I., B. Okumus, C. Joo, T. Ha, "Fueling Protein-DNA Interactions Inside Porous Nanocontainers", PNAS 104, 12646-12650 (2007) ( pdf )
  • Roy, R. A. G. Kozlov, T. M. Lohman and T. Ha, "Dynamic Structural Rearrangments between DNA Binding Modes of E. coli SSB protein", J. of Mol. Biology 369(5), 1244-1257 (2007) ( pdf )
  • Arluison, V., S. Hohng, R. Roy, O. Pellegrini, P. Regnier and T. Ha, "Spectroscopic Observation of RNA Chaperone Activities of Hfq in Post-transcriptional Regulation by a Small Non-coding RNA", Nuc. Acids Res. 35, 999-1006 (2007) ( pdf )
  • Cornish P. and T. Ha, "A Survey of Single Molecule Techniques in Chemical Biology", ACS Chemical Biology 2, 53-61 (2007) ( pdf )



  • Yoon, T., B. Okumus, F. Zhang, Y.K. Shin and T. Ha, "Multiple Intermediates in SNARE-induced Membrane Fusion", PNAS 103, 19731-19736 (2006) ( pdf )
  • Rasnik, I., S. A. McKinney, and T. Ha, "Nonblinking and Long-lasting Single Molecule Fluorescence Imaging", Nature Methods 3(11), 891-893 (2006) ( pdf )
  • Joo, C., S. A McKinney, M. Nakamura, I. Rasnik, S. Myong, and T. Ha, "Real Time Observation of RecA Filament Dynamics with Single Monomer Resolution", Cell 126, 515-527 (2006) ( pdf )
  • McKinney, S. A., C. Joo, and T. Ha, "Analysis of Single Molecule FRET Trajectories using Hidden Markov Modeling", Biophys. J. 91, 1941-1951 (2006) ( pdf )
  • Rasnik, I., S. Myong, and T. Ha, "Unraveling Helicase Mechanisms One Molecule at a Time", Nucl. Acids Res. 34, 4225-4231 (2006) ( pdf )
  • Lin, Y., C. E. Guzman, M. C. McKinney, S. K. Nair, T. Ha, and I. K. O. Cann, "Methanosarcina Acetivorans Flap Endonuclease 1 Activity is Inhibited by a Cognate Single-stranded-DNA-binding Protein", J. Bacteriology 188, 6153-6167 (2006) ( pdf )
  • Yu, J., T. Ha, and K. Schulten, "Structure-based Model of the Stepping Motor of PcrA Helicase", Biophys. J. 19, 2091-2114 (2006) ( pdf )
  • Toprak, E., J. Enderlein, Sh. Syed, S. McKinney, R. G. Perschek, T. Ha, Y. E. Goldman, and P. R. Selvin, "Defocused Orientation and Position Imaging (DOPI) of Myosin V", Proc. Nat. Acad. Sci. U.S.A. 103, 6495-6499 (2006) ( pdf )
  • Myong, S., B. Stevens, and T. Ha, "Bridging Conformational Dynamics and Function using Single-Molecule Spectroscopy", Structure 14, 633-643 (2006) ( pdf )
  • Buranachai, C., S. A. McKinney, and T. Ha, "Single Molecule Nanometronome", Nano Letters 102, 18938-18943 (2006) ( pdf )



  • Lee, J. Y., B. Okumus, D. S. Kim, and T. Ha, "Extreme Conformational Diversity in Human Telomeric DNA", Proc. Nat. Acad. Sci. U.S.A. 102, 18938-18943 (2005) ( pdf )
  • Myong, S., I. Rasnik, C. Joo, T. M. Lohman, and T. Ha, "Repetitive Shuttling of a Motor Protein on DNA", Nature 437, 1321-1325 (2005) ( pdf )
  • Rasnik, I., S. A. McKinney, and T. Ha, "Surfaces and Orientations: Much to FRET about?", Accounts of Chemical Research 38, 542-548 (2005) ( pdf )
  • Balci, H., T. Ha, H. L. Sweeney, and P. R. Selvin, "Interhead Distance Measurements in Myosin VI via SHRImP Support a Simplified Hand-over-hand Model", Biophys. J. 89, 413-417 (2005) ( pdf )
  • McKinney, S. A., A. Freeman, D. M. J. Lilley and T. Ha, "Observing Spontaneous Branch Migration of Holliday Junctions One Step at a Time", Proc. Nat. Acad. Sci. U.S.A. 102, 5715-5720 (2005) ( pdf )
  • Robbins, J.B., M. C. McKinney, C. E. Guzman, B. Sriratana, S. Fitz-Gibbon, T. Ha, and I. K. O. Cann, "The Euryarchaeota: Nature\'s Medium for Engineering of Single-stranded DNA Binding Proteins", J. Biol. Chem. 280, 15325-15339 (2005) ( pdf )
  • Hohng S. and T. Ha, "Single-molecule Quantum Dot Fluorescence Resonance Energy Transfer", ChemPhysChem 6(5), 956-960 (2005) ( pdf )
  • Liu, J., A. C. Declais, S. A. McKinney, T. Ha, D. G. Norman, and D. M. J. Lilley, "Stereospecific Effects Determine the Structure of a Four-way DNA Junction", Chem. Biology 12, 217-218 (2005) ( pdf )



  • Yu, J., T. Ha, and K. Schulten, "Conformational Model of the Holliday Junction Transition Deduced from Molecular Dynamics Simulations", Nuc. Acids Res. 32(22), 6683-6695 (2004) ( pdf )
  • Nahas, M. K., T. J. Wilson, S. Hohng, K. Jarvie, D. M. J. Lilley and T. Ha, "Observation of Internal Cleavage and Ligation Reactions of a Ribozyme", Nature Structural & Molecular Biology 11(11), 1107-1113 (2004) ( pdf )
  • Okumus, B., T. J. Wilson, D. M. J. Lilley, and T. Ha, "Vesicle Encapsulation Studies Reveal that Single Molecule Ribozyme Heterogeneities are Intrinsic", Biophys. J. 87(4), 2798-2806 (2004) ( pdf )
  • Hohng, S., C. Joo, and T. Ha, "Single-Molecule Three-color FRET", Biophys. J. 87(2), 1328-1337 (2004) ( pdf )
  • Gordon, M. P., T. Ha, and P. R. Selvin, "Single Molecule High Resolution Imaging with Photobleaching", Proc. Natl. Acad. Sci. U.S.A. 101(17), 6462-6465 (2004) ( pdf )
  • Ha, T., "Structural Dynamics and Processing of Nucleic Acids Revealed by Single Molecule Spectroscopy", Biochemistry 43(14), 4055-4063 (2004) ( pdf )
  • Joo, C., S. A. McKinney, D. M. J. Lilley and T. Ha, "Exploring Rare Conformational Species and Ionic Effects in DNA Holliday Junctions using Single-molecule Spectroscopy", J. of Molecular Biol. 341(3), 739-751 (2004) ( pdf )
  • Hohng S. and T. Ha, "Near-complete Suppression of Quantum Dot Blinking in Ambient Conditions", J. Am. Chem. Soc. 126(5), 1324-1325 (2004) ( pdf )
  • Stevens, B. C. and T. Ha, "Discrete and Heterogeneous Rotational Dynamics of Single Membrane Probe Dyes in Gel Phase Supported Bilayers", J.of Chem. Physics 120(6), 2020-2029 (2004) ( pdf )
  • Rasnik, I., S. Myong, W. Cheng, T. M. Lohman, and T. Ha, "DNA-binding Orientation and Domain Conformation of the E. Coli Rep Helicase Monomer Bound to a Partial Duplex Junction: Single-molecule Studies of Fluorescently Labeled Enzymes", J. of Mol. Biology 336(2), 395-408 (2004) ( pdf )
  • Hohng, S., E. Tan, T. J. Wilson, R. M. Clegg, D. M. J. Lilley, and T. Ha, "Conformational Flexibility of Four-way Junctions in RNA", J. Mol. Biol. 336(1), 69-79 (2004) ( pdf )
  • McKinney, S. A., E. Tan, T. J. Wilson, M. K. Nahas, A. C. Declias, R. M. Clegg, D. M. J. Lilley, and T. Ha, "Single Molecule Studies of DNA and RNA Four-way Junctions", Biochem. Soc. Transactions 32, 41-45 (2004) ( pdf )
  • Robbins, J. B., M. C. Murphy, B. A. White, R. I. Mackie, T. Ha, and I. K. O. Cann, "Functional Analysis of Multiple Single-stranded DNA-binding Proteins from Methanosarcina Acetivorans and their Effects of DNA Synthesis by DNA Polymerase BI", J. Biol. Chem. 279(8), 6315-6326 (2004) ( pdf )
  • Murphy, M. C., I. Rasnik, W. Cheng, T. M. Lohman, and T. Ha, "Probing Single Stranded DNA Conformational Flexibility using Fluorescence Spectroscopy", Biophys. J. 86(4), 2530-2537 (2004) ( pdf )



  • Tan, E., T. J. Wilson, M. K. Nahas, R. M. Clegg, D. M. J. Lilley, and T. Ha, "A Four-way Junction Accelerates Hairpin Ribozyme Folding via a Discrete Intermediate", Proc. Natl. Acad. Sci. U.S.A. 100(16), 9308 (2003) ( pdf )
  • Yildiz, A., J. Forkey, S. A. McKinney, T. Ha, Y. Goldman, and P. R. Selvin, "Myosin V Walks Hand over Hand: Single Fluorophore Imaging with 1.5 Nanometer Localization", Science 300(5628), 2061-2065 (2003) ( pdf )
  • Ha, T., and J. Xu, "Photodestruction Intermediates Probed by an Adjacent Reporter Molecule", Phys. Rev. Lett. 90(22), 223002 (1-4) (2003) ( pdf )
  • McKinney, S. A., A. C. Declais, D. M. J. Lilley, and T. Ha, "Structural Dynamics of Individual Holiday Junctions", Nature Structural Biology 10(2), 93-97 (2003) ( pdf )



  • Johnson, J. M., T. Ha, S. Chu, S. G. Boxer, "Early Steps of Supported Bilayer Formation Probed by Single Vesicle Fluorescence Assays", Biophys J. 419(6907), 3371-3379 (2002)
  • Ha, T., I. Rasnik, W. Cheng, H. P. Babcock, G. Gauss, T. M. Lohman, and S. Chu, "Initiation and Re-initiation of DNA Unwinding by the Echerichia Coli Rep Helicase", Nature 419(6907), 638-641 (2002) ( pdf )



  • Ha, T. , "Single Molecule Fluorescent Methods for Nucleic Acid Studies", Current Opinion in Structural Biology 11, 287 (2001) ( pdf )

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