Keywords
Last Name

Thomas D. Tullius, PhD

TitleProfessor
InstitutionBoston University College of Arts and Sciences
DepartmentChemistry
Address24 Cummington Mall
Boston MA 02215
Phone(617) 353-2482
ORCID ORCID Icon0000-0003-4425-796X
Other Positions
TitleProfessor
InstitutionBoston University School of Medicine
DepartmentPharmacology & Experimental Therapeutics

TitleDirector
InstitutionBoston University
DepartmentBioinformatics Graduate Program

 Research Expertise & Professional Interests
Tom Tullius conducts research in genomics, structural biology, and biophysical chemistry. In addition to Chemistry, he is Professor of Pharmacology and Professor of Experimental Therapeutics in the Boston University School of Medicine. He is an elected Fellow of the American Association for the Advancement of Science and he is on the Editorial Advisory Board of the Chemistry Central Journal. Professor Tullius is a faculty affiliate and Director of the Boston University Bioinformatics Program.

The Tullius Group introduced hydroxyl radical footprinting, which is widely used for the structural study of DNA, DNA-protein complexes, and RNA. They investigate the connection between structural properties of DNA and genomics, including evolutionary selection for DNA structure in the human genome. Their human genome studies were initiated with funding from the ENCODE (Encyclopedia of DNA Elements) Pilot Project, which was organized by the National Human Genome Research Institute of the NIH to discover functional elements in the human genome.

Measurement of the Deuterium Kinetic Isotope Effect on Hydroxyl Radical Cleavage of RNA aims to synthesize a complete set of nucleoside and deoxynucleoside triphosphates specifically deuterated at each sugar carbon atom. The deuterated nucleoside triphosphates are used in kinetic isotope effect experiments on hydroxyl radical cleavage of RNA, to provide more detailed information on the structural features of RNA to which the hydroxyl radical is sensitive. The goal of this work is the development of a chemical probe of RNA structure of unprecedented resolution.

Genome damage and aging: whole-genome maps of oxidative DNA lesions at single-nucleotide resolution investigates a new way to map, at single nucleotide resolution for an entire genome, the sites of oxidative damage that are induced in the DNA backbone by the hydroxyl radical. The study uses an advanced sequencing platform to comprehensively identify sites of DNA strand breaks. With these experiments it is possible to visualize, at single-nucleotide resolution, what parts of a genome are sensitive to attack by the hydroxyl radical and what parts are resistant. This work will provide unique new information on how oxidative damage affects the genome and so contributes to aging.

Techniques & Resources:

ORChID (OH Radical Cleavage Intensity Database) – Database of experimentally determined hydroxyl radical cleavage patterns of naked DNA molecules. Algorithm to predict the cleavage pattern of any DNA sequence.

ORChID in the UCSC Genome Browser – ORChID values predicted for the human genome. The data is viewable and available for download from the UCSC genome browser.

Chai regions in the UCSC Genome Browser – Chai is a structure-informed evolutionary sequence constraint detection algorithm. Chai-identified regions are available from the UCSC genome browser.

 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Chiu TP, Yang L, Zhou T, Main BJ, Parker SC, Nuzhdin SV, Tullius TD, Rohs R. 28 GBshape: a genome browser database for DNA shape annotations. J Biomol Struct Dyn. 2015; 33 Suppl 1:16. PMID: 26103240.
    View in: PubMed
  2. Chiu TP, Yang L, Zhou T, Main BJ, Parker SC, Nuzhdin SV, Tullius TD, Rohs R. GBshape: a genome browser database for DNA shape annotations. Nucleic Acids Res. 2015 Jan; 43(Database issue):D103-9. PMID: 25326329.
    View in: PubMed
  3. Ingle S, Azad RN, Jain SS, Tullius TD. Chemical probing of RNA with the hydroxyl radical at single-atom resolution. Nucleic Acids Res. 2014 Nov 10; 42(20):12758-67. PMID: 25313156.
    View in: PubMed
  4. Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A, Tolstorukov MY, Appert A, Parker SC, Gu T, Kundaje A, Riddle NC, Bishop E, Egelhofer TA, Hu SS, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RA, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM, Strome S, Elgin SC, Liu XS, Lieb JD, Ahringer J, Karpen GH, Park PJ. Comparative analysis of metazoan chromatin organization. Nature. 2014 Aug 28; 512(7515):449-52. PMID: 25164756.
    View in: PubMed
  5. Bishop EP, Rohs R, Parker SC, West SM, Liu P, Mann RS, Honig B, Tullius TD. A map of minor groove shape and electrostatic potential from hydroxyl radical cleavage patterns of DNA. ACS Chem Biol. 2011 Dec 16; 6(12):1314-20. PMID: 21967305.
    View in: PubMed
  6. Parker SC, Tullius TD. DNA shape, genetic codes, and evolution. Curr Opin Struct Biol. 2011 Jun; 21(3):342-7. PMID: 21439813.
    View in: PubMed
  7. Parker SC, Harlap A, Tullius TD. A computational method to search for DNA structural motifs in functional genomic elements. Methods Mol Biol. 2011; 759:367-79. PMID: 21863498.
    View in: PubMed
  8. Parker SC, Hansen L, Abaan HO, Tullius TD, Margulies EH. Local DNA topography correlates with functional noncoding regions of the human genome. Science. 2009 Apr 17; 324(5925):389-92. PMID: 19286520.
    View in: PubMed
  9. Parker SC, Margulies EH, Tullius TD. The relationship between fine scale DNA structure, GC content, and functional elements in 1% of the human genome. Genome Inform. 2008; 20:199-211. PMID: 19425134.
    View in: PubMed
  10. Jain SS, Tullius TD. Footprinting protein-DNA complexes using the hydroxyl radical. Nat Protoc. 2008; 3(6):1092-1100. PMID: 18546600.
    View in: PubMed
  11. Wang Q, Tullius TD, Levin JR. Effects of discontinuities in the DNA template on abortive initiation and promoter escape by Escherichia coli RNA polymerase. J Biol Chem. 2007 Sep 14; 282(37):26917-27. PMID: 17650506.
    View in: PubMed
  12. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007 Jun 14; 447(7146):799-816. PMID: 17571346.
    View in: PubMed
  13. Greenbaum JA, Parker SC, Tullius TD. Detection of DNA structural motifs in functional genomic elements. Genome Res. 2007 Jun; 17(6):940-6. PMID: 17568009.
    View in: PubMed
  14. Greenbaum JA, Pang B, Tullius TD. Construction of a genome-scale structural map at single-nucleotide resolution. Genome Res. 2007 Jun; 17(6):947-53. PMID: 17568010.
    View in: PubMed
  15. Danford AJ, Wang D, Wang Q, Tullius TD, Lippard SJ. Platinum anticancer drug damage enforces a particular rotational setting of DNA in nucleosomes. Proc Natl Acad Sci U S A. 2005 Aug 30; 102(35):12311-6. PMID: 16116097.
    View in: PubMed
  16. Tullius TD, Greenbaum JA. Mapping nucleic acid structure by hydroxyl radical cleavage. Curr Opin Chem Biol. 2005 Apr; 9(2):127-34. PMID: 15811796.
    View in: PubMed
  17. Deardorff D, Dorhout P, Haegel N, Iverson BL, Morrison M, Pladziewicz J, Selen M, Tullius TD, Zwier TS. Research Corporation and John Schaefer. Science. 2004 Nov 12; 306(5699):1133. PMID: 15539585.
    View in: PubMed
  18. Guo H, Tullius TD. Gapped DNA is anisotropically bent. Proc Natl Acad Sci U S A. 2003 Apr 1; 100(7):3743-7. PMID: 12644712.
    View in: PubMed
  19. Chen B, Jamieson ER, Tullius TD. A general synthesis of specifically deuterated nucleotides for studies of DNA and RNA. Bioorg Med Chem Lett. 2002 Nov 4; 12(21):3093-6. PMID: 12372509.
    View in: PubMed
  20. Frazee RW, Taylor JA, Tullius TD. Interchange of DNA-binding modes in the deformed and ultrabithorax homeodomains: a structural role for the N-terminal arm. J Mol Biol. 2002 Nov 1; 323(4):665-83. PMID: 12419257.
    View in: PubMed
  21. Tullius TD. Probing DNA structure with hydroxyl radicals. Curr Protoc Nucleic Acid Chem. 2002 Feb; Chapter 6:Unit 6.7. PMID: 18428898.
    View in: PubMed
  22. Levin JR, Blake JJ, Ganunis RA, Tullius TD. The roles of specific template nucleosides in the formation of stable transcription complexes by Escherichia coli RNA polymerase. J Biol Chem. 2000 Mar 10; 275(10):6885-93. PMID: 10702248.
    View in: PubMed
  23. Widlund HR, Kuduvalli PN, Bengtsson M, Cao H, Tullius TD, Kubista M. Nucleosome structural features and intrinsic properties of the TATAAACGCC repeat sequence. J Biol Chem. 1999 Nov 5; 274(45):31847-52. PMID: 10542209.
    View in: PubMed
  24. Jamison McDaniels CP, Jensen LT, Srinivasan C, Winge DR, Tullius TD. The yeast transcription factor Mac1 binds to DNA in a modular fashion. J Biol Chem. 1999 Sep 17; 274(38):26962-7. PMID: 10480908.
    View in: PubMed
  25. Balasubramanian B, Pogozelski WK, Tullius TD. DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone. Proc Natl Acad Sci U S A. 1998 Aug 18; 95(17):9738-43. PMID: 9707545.
    View in: PubMed
  26. Pogozelski WK, Tullius TD. Oxidative Strand Scission of Nucleic Acids: Routes Initiated by Hydrogen Abstraction from the Sugar Moiety. Chem Rev. 1998 May 7; 98(3):1089-1108. PMID: 11848926.
    View in: PubMed
  27. Draganescu A, Tullius TD. The DNA binding specificity of engrailed homeodomain. J Mol Biol. 1998 Feb 27; 276(3):529-36. PMID: 9551094.
    View in: PubMed
  28. Eijkelenboom AP, van den Ent FM, Vos A, Doreleijers JF, Hård K, Tullius TD, Plasterk RH, Kaptein R, Boelens R. The solution structure of the amino-terminal HHCC domain of HIV-2 integrase: a three-helix bundle stabilized by zinc. Curr Biol. 1997 Oct 1; 7(10):739-46. PMID: 9368756.
    View in: PubMed
  29. Shadle SE, Allen DF, Guo H, Pogozelski WK, Bashkin JS, Tullius TD. Quantitative analysis of electrophoresis data: novel curve fitting methodology and its application to the determination of a protein-DNA binding constant. Nucleic Acids Res. 1997 Feb 15; 25(4):850-60. PMID: 9016637.
    View in: PubMed
  30. Ganunis RM, Guo H, Tullius TD. Effect of the crystallizing agent 2-methyl-2,4-pentanediol on the structure of adenine tract DNA in solution. Biochemistry. 1996 Oct 29; 35(43):13729-32. PMID: 8901514.
    View in: PubMed
  31. Draganescu A, Tullius TD. Targeting of nucleic acids by iron complexes. Met Ions Biol Syst. 1996; 33:453-84. PMID: 8742852.
    View in: PubMed
  32. Tullius T. Homeodomains: together again for the first time. Structure. 1995 Nov 15; 3(11):1143-5. PMID: 8591025.
    View in: PubMed
  33. Kimball AS, Kimball ML, Jayaram M, Tullius TD. Chemical probe and missing nucleoside analysis of Flp recombinase bound to the recombination target sequence. Nucleic Acids Res. 1995 Aug 11; 23(15):3009-17. PMID: 7659525.
    View in: PubMed
  34. Draganescu A, Levin JR, Tullius TD. Homeodomain proteins: what governs their ability to recognize specific DNA sequences? J Mol Biol. 1995 Jul 28; 250(5):595-608. PMID: 7623378.
    View in: PubMed
  35. Kuduvalli PN, Townsend CA, Tullius TD. Cleavage by calicheamicin gamma 1I of DNA in a nucleosome formed on the 5S RNA gene of Xenopus borealis. Biochemistry. 1995 Mar 28; 34(12):3899-906. PMID: 7696253.
    View in: PubMed
  36. Mah SC, Townsend CA, Tullius TD. Hydroxyl radical footprinting of calicheamicin. Relationship of DNA binding to cleavage. Biochemistry. 1994 Jan 18; 33(2):614-21. PMID: 8286393.
    View in: PubMed
  37. Kimball AS, Lee J, Jayaram M, Tullius TD. Sequence-specific cleavage of DNA via nucleophilic attack of hydrogen peroxide, assisted by Flp recombinase. Biochemistry. 1993 May 11; 32(18):4698-701. PMID: 8490015.
    View in: PubMed
  38. Bashkin J, Hayes JJ, Tullius TD, Wolffe AP. Structure of DNA in a nucleosome core at high salt concentration and at high temperature. Biochemistry. 1993 Mar 2; 32(8):1895-8. PMID: 8383529.
    View in: PubMed
  39. Price MA, Tullius TD. How the structure of an adenine tract depends on sequence context: a new model for the structure of TnAn DNA sequences. Biochemistry. 1993 Jan 12; 32(1):127-36. PMID: 8380329.
    View in: PubMed
  40. Hayes JJ, Tullius TD. Structure of the TFIIIA-5 S DNA complex. J Mol Biol. 1992 Sep 20; 227(2):407-17. PMID: 1404361.
    View in: PubMed
  41. Price MA, Tullius TD. Using hydroxyl radical to probe DNA structure. Methods Enzymol. 1992; 212:194-219. PMID: 1325598.
    View in: PubMed
  42. Hayes JJ, Bashkin J, Tullius TD, Wolffe AP. The histone core exerts a dominant constraint on the structure of DNA in a nucleosome. Biochemistry. 1991 Aug 27; 30(34):8434-40. PMID: 1653013.
    View in: PubMed
  43. Dixon WJ, Hayes JJ, Levin JR, Weidner MF, Dombroski BA, Tullius TD. Hydroxyl radical footprinting. Methods Enzymol. 1991; 208:380-413. PMID: 1664026.
    View in: PubMed
  44. Tullius TD. Bioinorganic chemistry. J Cell Biochem. 1991 Jan; 45(1):5-6. PMID: 1706345.
    View in: PubMed
  45. Tullius TD. DNA footprinting with the hydroxyl radical. Free Radic Res Commun. 1991; 12-13 Pt 2:521-9. PMID: 1648010.
    View in: PubMed
  46. Guo Q, Lu M, Churchill ME, Tullius TD, Kallenbach NR. Asymmetric structure of a three-arm DNA junction. Biochemistry. 1990 Dec 11; 29(49):10927-34. PMID: 2176888.
    View in: PubMed
  47. Hayes JJ, Tullius TD, Wolffe AP. The structure of DNA in a nucleosome. Proc Natl Acad Sci U S A. 1990 Oct; 87(19):7405-9. PMID: 2170977.
    View in: PubMed
  48. Kimball A, Guo Q, Lu M, Cunningham RP, Kallenbach NR, Seeman NC, Tullius TD. Construction and analysis of parallel and antiparallel Holliday junctions. J Biol Chem. 1990 Sep 05; 265(25):15348. PMID: 2394725.
    View in: PubMed
  49. Buchman C, Skroch P, Dixon W, Tullius TD, Karin M. A single amino acid change in CUP2 alters its mode of DNA binding. Mol Cell Biol. 1990 Sep; 10(9):4778-87. PMID: 2167439.
    View in: PubMed
  50. Churchill ME, Tullius TD, Klug A. Mode of interaction of the zinc finger protein TFIIIA with a 5S RNA gene of Xenopus. Proc Natl Acad Sci U S A. 1990 Jul; 87(14):5528-32. PMID: 2164687.
    View in: PubMed
  51. Churchill ME, Hayes JJ, Tullius TD. Detection of drug binding to DNA by hydroxyl radical footprinting. Relationship of distamycin binding sites to DNA structure and positioned nucleosomes on 5S RNA genes of Xenopus. Biochemistry. 1990 Jun 26; 29(25):6043-50. PMID: 1696501.
    View in: PubMed
  52. Kimball A, Guo Q, Lu M, Cunningham RP, Kallenbach NR, Seeman NC, Tullius TD. Construction and analysis of parallel and antiparallel Holliday junctions. J Biol Chem. 1990 Apr 25; 265(12):6544-7. PMID: 2157702.
    View in: PubMed
  53. Hayes JJ, Kam L, Tullius TD. Footprinting protein-DNA complexes with gamma-rays. Methods Enzymol. 1990; 186:545-9. PMID: 2172714.
    View in: PubMed
  54. Hayes JJ, Tullius TD. The missing nucleoside experiment: a new technique to study recognition of DNA by protein. Biochemistry. 1989 Nov 28; 28(24):9521-7. PMID: 2611245.
    View in: PubMed
  55. Kimball AS, Milman G, Tullius TD. High-resolution footprints of the DNA-binding domain of Epstein-Barr virus nuclear antigen 1. Mol Cell Biol. 1989 Jun; 9(6):2738-42. PMID: 2548088.
    View in: PubMed
  56. Shafer GE, Price MA, Tullius TD. Use of the hydroxyl radical and gel electrophoresis to study DNA structure. Electrophoresis. 1989 May-Jun; 10(5-6):397-404. PMID: 2504579.
    View in: PubMed
  57. Hayes J, Tullius TD, Wolffe AP. A protein-protein interaction is essential for stable complex formation on a 5 S RNA gene. J Biol Chem. 1989 Apr 15; 264(11):6009-12. PMID: 2703476.
    View in: PubMed
  58. Tullius TD. Physical studies of protein-DNA complexes by footprinting. Annu Rev Biophys Biophys Chem. 1989; 18:213-37. PMID: 2660824.
    View in: PubMed
  59. Chen JH, Churchill ME, Tullius TD, Kallenbach NR, Seeman NC. Construction and analysis of monomobile DNA junctions. Biochemistry. 1988 Aug 9; 27(16):6032-8. PMID: 3191106.
    View in: PubMed
  60. Churchill ME, Tullius TD, Kallenbach NR, Seeman NC. A Holliday recombination intermediate is twofold symmetric. Proc Natl Acad Sci U S A. 1988 Jul; 85(13):4653-6. PMID: 3387432.
    View in: PubMed
  61. Tullius TD. DNA footprinting with hydroxyl radical. Nature. 1988 Apr 14; 332(6165):663-4. PMID: 2833707.
    View in: PubMed
  62. Vrana KE, Churchill ME, Tullius TD, Brown DD. Mapping functional regions of transcription factor TFIIIA. Mol Cell Biol. 1988 Apr; 8(4):1684-96. PMID: 2837652.
    View in: PubMed
  63. Burkhoff AM, Tullius TD. Structural details of an adenine tract that does not cause DNA to bend. Nature. 1988 Feb 4; 331(6155):455-7. PMID: 3340190.
    View in: PubMed
  64. Burkhoff AM, Tullius TD. The unusual conformation adopted by the adenine tracts in kinetoplast DNA. Cell. 1987 Mar 27; 48(6):935-43. PMID: 3030560.
    View in: PubMed
  65. Tullius TD, Dombroski BA, Churchill ME, Kam L. Hydroxyl radical footprinting: a high-resolution method for mapping protein-DNA contacts. Methods Enzymol. 1987; 155:537-58. PMID: 2828876.
    View in: PubMed
  66. Tullius TD, Dombroski BA. Hydroxyl radical "footprinting": high-resolution information about DNA-protein contacts and application to lambda repressor and Cro protein. Proc Natl Acad Sci U S A. 1986 Aug; 83(15):5469-73. PMID: 3090544.
    View in: PubMed
  67. Tullius TD, Dombroski BA. Iron(II) EDTA used to measure the helical twist along any DNA molecule. Science. 1985 Nov 8; 230(4726):679-81. PMID: 2996145.
    View in: PubMed
  68. Frank P, Licht A, Tullius TD, Hodgson KO, Pecht I. A selenomethionine-containing azurin from an auxotroph of Pseudomonas aeruginosa. J Biol Chem. 1985 May 10; 260(9):5518-25. PMID: 2985597.
    View in: PubMed
  69. Tullius TD, Lippard SJ. Ethidium bromide changes the nuclease-sensitive DNA binding sites of the antitumor drug cis-diamminedichloroplatinum(II). Proc Natl Acad Sci U S A. 1982 Jun; 79(11):3489-92. PMID: 6954494.
    View in: PubMed
  70. Ushay HM, Tullius TD, Lippard SJ. Inhibition of the BamHI cleavage and unwinding of pBR322 deoxyribonucleic acid by the antitumor drug cis-dichlorodiammineplatinum(II). Biochemistry. 1981 Jun 23; 20(13):3744-8. PMID: 6268142.
    View in: PubMed
  71. Tullius TD, Frank P, Hodgson KO. Characterization of the blue copper site in oxidized azurin by extended x-ray absorption fine structure: Determination of a short Cu-S distance. Proc Natl Acad Sci U S A. 1978 Sep; 75(9):4069-73. PMID: 16592557.
    View in: PubMed
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