725 N. Wolfe St.
Baltimore, MD 21205
My research is focused on pushing the limits of single-molecule detection methods to study complex biological systems. His group develops state-of-the-art biophysical techniques (e.g., multicolor fluorescence, super-resolution imaging, combined force and fluorescence spectroscopy, vesicular encapsulation, single-molecule pull-down) and applies them to study diverse protein–nucleic acid and protein-protein complexes, and mechanical perturbation and response of these systems both in vitro and in vivo.
T. Ha, Th. Enderle, D.F. Ogletree, D.S. Chemla, P. Selvin, and S. Weiss, “Probing the interaction between two single molecules: Fluorescence resonance energy transfer between a single donor and a single acceptor ,” Proc. Natl. Acad. Sci. U.S.A. 93, 6264 (1996).
S. Myong, M. M. Bruno, A. M. Pyle and T. Ha, “Spring-loaded mechanism of DNA unwinding by HCV NS3 helicase,” Science 317, 513-516 (2007).
S. Hohng, 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).
R. Roy, A. Kozlov, T. M. Lohman and T. Ha, “SSB protein diffusion on single stranded DNA stimulates RecA filament formation,” Nature 461(7267), 1092-1097 (2009).
A. Jain, R. Liu, B. Ramani, E. Arauz, Y. Ishitsuka, K. Ragunathan, J. Park, J. Chen, Y. K. Xiang and T. Ha, “Probing cellular protein complexes using single-molecule pull-down”, Nature 473, 484-488 (2011).
R. Vafabakhsh and T. Ha, “Extreme bendability of DNA less than 100 base pairs long revealed by single molecule cyclization”, Science, 337, 1097-1101 (2012).
X. Wang and T. Ha, “Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling”, Science 340, 991-994 (2013).
T. Ngo, Q. Zhang, R. Zhou, J. G. Yodh and T. Ha, “Asymmetric unwrapping of nucleosomes under tension directed by DNA local flexibility”, Cell 160, 1135-1144 (2015).
J. Fei, D. Singh, Q. Zhang, S. Park, D. Balasubramanian, I. Golding, C. K. Vanderpool and T. Ha, “Determination of in vivo target search kinetics of regulatory noncoding RNA”, Science 347, 1371-1374 (2015).
S. Arslan, R. Khafizov, C. D. Thomas, Y. R. Chemla and T. Ha, “Engineering of a superhelicase through conformational control”, Science 348, 344-347 (2015).
V. C. Luca, B.C. Kim, C. Ge, S. Kakuda, D. Wu, M. Roein-Peikar, R. S. Haltiwanger, C. Zhu, T. Ha and K. C. Garcia, “Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity”, Science 355, 1320-1324 (2017).
D. Singh, Y. Wang, J. Mallon, O. Yang, J. Fei, A. Poddar, D. Ceylan, S. Bailey and T. Ha, “Mechanisms of improved specificity of engineered Cas9s revealed by single molecule analysis”, Nature Structural & Molecular Biology 25, 347-354 (2018).
Y. Liu, R. S. Zou, S. He, Y. Nihongaki, X. Li, S. Razavi, B. Wu and T. Ha, “Very fast CRISPR on demand”, Science 368, 1265–1269 (2020).
A. Basu, D.G. Bobrovnikov, Z. Qureshi, T. Kayikcioglu, T.T.M. Ngo, A. Ranjan, S. Eustermann, B. Cieza, M.T. Morgan, M. Hejna, H.T. Rube, K.P. Hopfner, C. Wolberger, J.S. Song and T. Ha, “Measuring DNA mechanics on the genome scale” Nature 589, 462-467 (2021).
R. S. Zou, Y. Liu, B. Wu and T. Ha, “Cas9 deactivation with photocleavable guide RNAs”, Molecular Cell 81:1553-1565 (2021).
Y. Wang, W.T. Cottle, H. Wang, X.A. Feng, J. Mallon, M. Gavrilov, S. Bailey and T. Ha, “Genome Oligopaint via Local Denaturing Fluorescence In situ Hybridization”, Molecular Cell 81:1566-1577 (2021).