Information

Related Research Units

Genetics and Genomics Research
PCMM Research

Research Overview

The main focus of his research is the investigation of genomic caretakers, the molecular entities that play a crucial role in preserving the integrity of the genome and in averting severe risks to human health, such as cancer. A new era of targeted therapies is revolutionizing cancer treatment by targeting the underlying molecular mechanism of the disease, and it is now a feasible objective to drastically reduce mortality from cancer, making it a manageable condition. He explores the fundamental mechanisms of the proteins that are indispensable in preventing the onset of cancer by integrating cutting-edge single-molecule techniques and state-of-the-art biology.

Many biological reactions are too intricate to fully comprehend using conventional ensemble techniques. At the most basic level, all biological reactions take place via the action of single enzymes, DNA or RNA molecules. His single-molecule techniques offer unprecedented data on elementary biological processes, enhancing our understanding and providing new paradigms. Most recently, he applied the mechanistic knowledge obtained through in vitro single-molecule measurements to develop innovative biotechnologies suitable for mammalian cells and employed next generation sequencing to develop high throughput biophysical assays.

Research Background

Dr. Taekjip Ha is a Senior Investigator of Program in Cellular and Molecular Medicine at Boston Children's Hospital and Professor of Pediatrics at Harvard Medical School. He is also an investigator with the Howard Hughes Medical Institute. He develops and uses single molecule and single cell measurement tools to study life at high resolution, with genome maintenance as research focus.

Dr. Ha received a bachelor in Physics from Seoul National University in 1990 and Physics Ph.D from University of California at Berkeley in 1996. After postdoctoral training at Stanford, he was a Physics professor at University of Illinois at Urbana-Champaign until 2015, Bloomberg Distinguished Professor of Biophysics and Biomedical Engineering at Johns Hopkins University until 2023.
Dr. Ha serves on Editorial Boards for Science. He is a member of the National Academy of Science and the National Academy of Medicine, and a fellow of the American Academy of Arts and Sciences. He received the 2011 HoAm Prize in Science and was elected as President of the Biophysical Society in 2021.

Publications

  1. A tubulin-binding protein that preferentially binds to GDP-tubulin and promotes GTP exchange. bioRxiv. 2024 Jul 15. View Abstract
  2. Single-Macromolecule Studies of Eukaryotic Genomic Maintenance. Annu Rev Phys Chem. 2024 Jun; 75(1):209-230. View Abstract
  3. GAGA zinc finger transcription factor searches chromatin by 1D-3D facilitated diffusion. bioRxiv. 2024 May 25. View Abstract
  4. Rapid Long-distance Migration of RPA on Single Stranded DNA Occurs Through Intersegmental Transfer Utilizing Multivalent Interactions. J Mol Biol. 2024 03 15; 436(6):168491. View Abstract
  5. Dynamic 1D Search and Processive Nucleosome Translocations by RSC and ISW2 Chromatin Remodelers. bioRxiv. 2024 Jan 15. View Abstract
  6. SIKs Regulate HDAC7 Stabilization and Cytokine Recall in Late-Stage T Cell Effector Differentiation. J Immunol. 2023 12 15; 211(12):1767-1782. View Abstract
  7. Single molecule studies of the native hair cell mechanosensory transduction complex. bioRxiv. 2023 Dec 12. View Abstract
  8. Electrostatic encoding of genome organization principles within single native nucleosomes. bioRxiv. 2023 Dec 09. View Abstract
  9. Enhanced mTORC1 signaling and protein synthesis in pathologic a-synuclein cellular and animal models of Parkinson's disease. Sci Transl Med. 2023 11 29; 15(724):eadd0499. View Abstract
  10. Bi-directional nucleosome sliding by the Chd1 chromatin remodeler integrates intrinsic sequence-dependent and ATP-dependent nucleosome positioning. Nucleic Acids Res. 2023 10 27; 51(19):10326-10343. View Abstract
  11. Mind your tag in single-molecule measurements. Cell Rep Methods. 2023 10 23; 3(10):100623. View Abstract
  12. Directing Uphill Strand Displacement with an Engineered Superhelicase. ACS Synth Biol. 2023 11 17; 12(11):3424-3432. View Abstract
  13. Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis. bioRxiv. 2023 Sep 24. View Abstract
  14. Helicase Activity Modulation with On-Demand Light-Based Conformational Control. J Am Chem Soc. 2023 10 04; 145(39):21253-21262. View Abstract
  15. Linking folding dynamics and function of SAM/SAH riboswitches at the single molecule level. Nucleic Acids Res. 2023 09 22; 51(17):8957-8969. View Abstract
  16. Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice. Nat Commun. 2023 09 16; 14(1):5759. View Abstract
  17. Bursting translation on single mRNAs in live cells. Mol Cell. 2023 Jul 06; 83(13):2276-2289.e11. View Abstract
  18. The START domain potentiates HD-ZIPIII transcriptional activity. Plant Cell. 2023 05 29; 35(6):2332-2348. View Abstract
  19. Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis. Nat Commun. 2023 05 20; 14(1):2888. View Abstract
  20. DNA Damage-Induced, S-Phase Specific Phosphorylation of Orc6 is Critical for the Maintenance of Genome Stability. Mol Cell Biol. 2023; 43(4):143-156. View Abstract
  21. Improving the sensitivity of in vivo CRISPR off-target detection with DISCOVER-Seq. Nat Methods. 2023 05; 20(5):706-713. View Abstract
  22. Reliability and accuracy of single-molecule FRET studies for characterization of structural dynamics and distances in proteins. Nat Methods. 2023 04; 20(4):523-535. View Abstract
  23. Mapping cellular responses to DNA double-strand breaks using CRISPR technologies. Trends Genet. 2023 07; 39(7):560-574. View Abstract
  24. Sniper2L is a high-fidelity Cas9 variant with high activity. Nat Chem Biol. 2023 08; 19(8):972-980. View Abstract
  25. Dimensional Reduction for Single-Molecule Imaging of DNA and Nucleosome Condensation by Polyamines, HP1a and Ki-67. J Phys Chem B. 2023 03 09; 127(9):1922-1931. View Abstract
  26. Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly. Am J Hum Genet. 2023 03 02; 110(3):499-515. View Abstract
  27. Single Molecule FRET Analysis of CRISPR Cas9 Single Guide RNA Folding Dynamics. J Phys Chem B. 2023 01 12; 127(1):45-51. View Abstract
  28. Achieving single nucleotide sensitivity in direct hybridization genome imaging. Nat Commun. 2022 12 15; 13(1):7776. View Abstract
  29. Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension. PNAS Nexus. 2023 Jan; 2(1):pgac270. View Abstract
  30. Deciphering the mechanical code of the genome and epigenome. Nat Struct Mol Biol. 2022 12; 29(12):1178-1187. View Abstract
  31. Single-molecule characterization of subtype-specific ß1 integrin mechanics. Nat Commun. 2022 12 03; 13(1):7471. View Abstract
  32. Engineered helicase replaces thermocycler in DNA amplification while retaining desired PCR characteristics. Nat Commun. 2022 10 23; 13(1):6312. View Abstract
  33. ß2-Integrin Adhesive Bond Tension under Shear Stress Modulates Cytosolic Calcium Flux and Neutrophil Inflammatory Response. Cells. 2022 09 09; 11(18). View Abstract
  34. Massively parallel genomic perturbations with multi-target CRISPR interrogates Cas9 activity and DNA repair at endogenous sites. Nat Cell Biol. 2022 Sep; 24(9):1433-1444. View Abstract
  35. Rtt105 regulates RPA function by configurationally stapling the flexible domains. Nat Commun. 2022 09 02; 13(1):5152. View Abstract
  36. Sequence-dependent mechanochemical coupling of helicase translocation and unwinding at single-nucleotide resolution. Proc Natl Acad Sci U S A. 2022 09 06; 119(36):e2202489119. View Abstract
  37. AAA?+?ATPase Thorase inhibits mTOR signaling through the disassembly of the mTOR complex 1. Nat Commun. 2022 08 17; 13(1):4836. View Abstract
  38. Pseudomonas-tailed lytic phages: genome mechanical analysis and putative correlation with virion morphogenesis yield. Future Microbiol. 2022 Sep; 17:1009-1026. View Abstract
  39. ATP binding facilitates target search of SWR1 chromatin remodeler by promoting one-dimensional diffusion on DNA. Elife. 2022 07 25; 11. View Abstract
  40. Membrane Ruffling is a Mechanosensor of Extracellular Fluid Viscosity. Nat Phys. 2022 Sep; 18(9):1112-1121. View Abstract
  41. Dynamin is primed at endocytic sites for ultrafast endocytosis. Neuron. 2022 09 07; 110(17):2815-2835.e13. View Abstract
  42. Vectorial folding of telomere overhang promotes higher accessibility. Nucleic Acids Res. 2022 06 24; 50(11):6271-6283. View Abstract
  43. Orc6 is a component of the replication fork and enables efficient mismatch repair. Proc Natl Acad Sci U S A. 2022 05 31; 119(22):e2121406119. View Abstract
  44. Engineering Functional Membrane-Membrane Interfaces by InterSpy. Small. 2023 03; 19(13):e2202104. View Abstract
  45. Catalytic DNA Polymerization Can Be Expedited by Active Product Release. Angew Chem Int Ed Engl. 2022 06 13; 61(24):e202114581. View Abstract
  46. Improving the specificity of nucleic acid detection with endonuclease-actuated degradation. Commun Biol. 2022 03 31; 5(1):290. View Abstract
  47. Coordinated DNA and histone dynamics drive accurate histone H2A.Z exchange. Sci Adv. 2022 03 11; 8(10):eabj5509. View Abstract
  48. Next generation single-molecule techniques: Imaging, labeling, and manipulation in vitro and in cellulo. Mol Cell. 2022 01 20; 82(2):304-314. View Abstract
  49. Characterization and in vitro testing of newly isolated lytic bacteriophages for the biocontrol of Pseudomonas aeruginosa. Future Microbiol. 2022 01; 17:111-141. View Abstract
  50. DNA sequence and methylation prescribe the inside-out conformational dynamics and bending energetics of DNA minicircles. Nucleic Acids Res. 2021 11 18; 49(20):11459-11475. View Abstract
  51. A viral genome packaging ring-ATPase is a flexibly coordinated pentamer. Nat Commun. 2021 11 12; 12(1):6548. View Abstract
  52. Single molecule methods for studying CRISPR Cas9-induced DNA unwinding. Methods. 2022 Aug; 204:319-326. View Abstract
  53. CRISPR deactivation in mammalian cells using photocleavable guide RNAs. STAR Protoc. 2021 Dec 17; 2(4):100909. View Abstract
  54. Light activation and deactivation of Cas9 for DNA repair studies. Methods Enzymol. 2021; 661:219-249. View Abstract
  55. In vitro Cleavage and Electrophoretic Mobility Shift Assays for Very Fast CRISPR. Bio Protoc. 2021 Sep 05; 11(17):e4138. View Abstract
  56. Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins. Nat Commun. 2021 07 15; 12(1):4339. View Abstract
  57. Molecular Nanomechanical Mapping of Histamine-Induced Smooth Muscle Cell Contraction and Shortening. ACS Nano. 2021 Jul 27; 15(7):11585-11596. View Abstract
  58. Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition. Nature. 2021 06; 594(7863):448-453. View Abstract
  59. Multicolor single-molecule FRET for DNA and RNA processes. Curr Opin Struct Biol. 2021 10; 70:26-33. View Abstract
  60. FRET-based dynamic structural biology: Challenges, perspectives and an appeal for open-science practices. Elife. 2021 03 29; 10. View Abstract
  61. Mechanical stress determines the configuration of TGFß activation in articular cartilage. Nat Commun. 2021 03 17; 12(1):1706. View Abstract
  62. Regeneration of PEG slide for multiple rounds of single-molecule measurements. Biophys J. 2021 05 04; 120(9):1788-1799. View Abstract
  63. Cas9 deactivation with photocleavable guide RNAs. Mol Cell. 2021 Apr 01; 81(7):1553-1565.e8. View Abstract
  64. Genome oligopaint via local denaturation fluorescence in situ hybridization. Mol Cell. 2021 Apr 01; 81(7):1566-1577.e8. View Abstract
  65. Effects of individual base-pairs on in vivo target search and destruction kinetics of bacterial small RNA. Nat Commun. 2021 02 08; 12(1):874. View Abstract
  66. DNA mechanics and its biological impact. J Mol Biol. 2021 03 19; 433(6):166861. View Abstract
  67. Stochastic Analysis Demonstrates the Dual Role of Hfq in Chaperoning E. coli Sugar Shock Response. Front Mol Biosci. 2020; 7:593826. View Abstract
  68. Real-time observation of Cas9 postcatalytic domain motions. Proc Natl Acad Sci U S A. 2021 Jan 12; 118(2). View Abstract
  69. ALS/FTLD-Linked Mutations in FUS Glycine Residues Cause Accelerated Gelation and Reduced Interactions with Wild-Type FUS. Mol Cell. 2020 Dec 17; 80(6):1139. View Abstract
  70. Measuring DNA mechanics on the genome scale. Nature. 2021 01; 589(7842):462-467. View Abstract
  71. ALS/FTLD-Linked Mutations in FUS Glycine Residues Cause Accelerated Gelation and Reduced Interactions with Wild-Type FUS. Mol Cell. 2020 11 19; 80(4):666-681.e8. View Abstract
  72. Increasing kinase domain proximity promotes MST2 autophosphorylation during Hippo signaling. J Biol Chem. 2020 11 20; 295(47):16166-16179. View Abstract
  73. COL2A1 Is a Novel Biomarker of Melanoma Tumor Repopulating Cells. Biomedicines. 2020 Sep 18; 8(9). View Abstract
  74. Real-time monitoring of single ZTP riboswitches reveals a complex and kinetically controlled decision landscape. Nat Commun. 2020 09 10; 11(1):4531. View Abstract
  75. Crystal structure and ligand-induced folding of the SAM/SAH riboswitch. Nucleic Acids Res. 2020 07 27; 48(13):7545-7556. View Abstract
  76. E. coli Rep helicase and RecA recombinase unwind G4 DNA and are important for resistance to G4-stabilizing ligands. Nucleic Acids Res. 2020 07 09; 48(12):6640-6653. View Abstract
  77. Force-dependent trans-endocytosis by breast cancer cells depletes costimulatory receptor CD80 and attenuates T cell activation. Biosens Bioelectron. 2020 Oct 01; 165:112389. View Abstract
  78. Very fast CRISPR on demand. Science. 2020 06 12; 368(6496):1265-1269. View Abstract
  79. Light-controlled twister ribozyme with single-molecule detection resolves RNA function in time and space. Proc Natl Acad Sci U S A. 2020 06 02; 117(22):12080-12086. View Abstract
  80. ORCA/LRWD1 Regulates Homologous Recombination at ALT-Telomeres by Modulating Heterochromatin Organization. iScience. 2020 May 22; 23(5):101038. View Abstract
  81. Just Took a DNA Test, Turns Out 100% Not That Phase. Mol Cell. 2020 04 16; 78(2):193-194. View Abstract
  82. Single molecule analysis of effects of non-canonical guide RNAs and specificity-enhancing mutations on Cas9-induced DNA unwinding. Nucleic Acids Res. 2019 12 16; 47(22):11880-11888. View Abstract
  83. Streamlining effects of extra telomeric repeat on telomeric DNA folding revealed by fluorescence-force spectroscopy. Nucleic Acids Res. 2019 12 02; 47(21):11044-11056. View Abstract
  84. Structural basis for DNA unwinding at forked dsDNA by two coordinating Pif1 helicases. Nat Commun. 2019 11 26; 10(1):5375. View Abstract
  85. Single-Molecule Analysis and Engineering of DNA Motors. Chem Rev. 2020 01 08; 120(1):36-78. View Abstract
  86. Nanomechanics and co-transcriptional folding of Spinach and Mango. Nat Commun. 2019 09 20; 10(1):4318. View Abstract
  87. Determinants of target prioritization and regulatory hierarchy for the bacterial small RNA SgrS. Mol Microbiol. 2019 10; 112(4):1199-1218. View Abstract
  88. Strategy for Compositional Analysis of the Hair Cell Mechanotransduction Complex Using TIRF Microscopy. Microsc Microanal. 2019 08; 25(Suppl 2):1266-1267. View Abstract
  89. Fight against background noise in stimulated emission depletion nanoscopy. Phys Biol. 2019 07 05; 16(5):051002. View Abstract
  90. Nuclear speckle fusion via long-range directional motion regulates speckle morphology after transcriptional inhibition. J Cell Sci. 2019 04 17; 132(8). View Abstract
  91. Extreme mechanical diversity of human telomeric DNA revealed by fluorescence-force spectroscopy. Proc Natl Acad Sci U S A. 2019 04 23; 116(17):8350-8359. View Abstract
  92. Functional instability allows access to DNA in longer transcription Activator-Like effector (TALE) arrays. Elife. 2019 02 27; 8. View Abstract
  93. Hexameric helicase G40P unwinds DNA in single base pair steps. Elife. 2019 01 28; 8. View Abstract
  94. Junction resolving enzymes use multivalency to keep the Holliday junction dynamic. Nat Chem Biol. 2019 03; 15(3):269-275. View Abstract
  95. Contractility kits promote assembly of the mechanoresponsive cytoskeletal network. J Cell Sci. 2019 01 16; 132(2). View Abstract
  96. Real-Time Measurement of Molecular Tension during Cell Adhesion and Migration Using Multiplexed Differential Analysis of Tension Gauge Tethers. ACS Biomater Sci Eng. 2019 Aug 12; 5(8):3856-3863. View Abstract
  97. Structural Mechanisms of Cooperative DNA Binding by Bacterial Single-Stranded DNA-Binding Proteins. J Mol Biol. 2019 01 18; 431(2):178-195. View Abstract
  98. Publisher Correction: Precision and accuracy of single-molecule FRET measurements-a multi-laboratory benchmark study. Nat Methods. 2018 Nov; 15(11):984. View Abstract
  99. Precision and accuracy of single-molecule FRET measurements-a multi-laboratory benchmark study. Nat Methods. 2018 09; 15(9):669-676. View Abstract
  100. Mimicking Co-Transcriptional RNA Folding Using a Superhelicase. J Am Chem Soc. 2018 08 15; 140(32):10067-10070. View Abstract

Contact Taekjip Ha

Print Profile