Bruce Alan Sullenger

Image of Bruce Alan Sullenger

Joseph W. and Dorothy W. Beard Professor of Experimental Surgery, in the School of Medicine

The main focus of my translational research laboratory is to develop RNA based therapeutic agents for the potential treatment of a range of diseases. To this end, we have and will continue to take advantage of the fact that RNA is not just a passive carrier of genetic instructions inside of cells during the conversion of information from DNA to RNA to protein. Rather, RNA is an extremely versatile biological macromolecule. Certian RNAs can bind to specific protiens with high affinities, while others can for catalytic centers and perform enzymatic reactions. These facets of RNA coupled with the ease with which RNA can be manipulated in vitro make it a very powerful and unique therapeutic agent whose potential is largely untapped. Durring our endeavors, we plan to work closely with the members of the Molecular Therapeutics program as well as other faculty at the Duke University Medical Center to expedite the development and testing of these therapeutics.

The specific aims of my laboratory are:

1. To isolate and characterize RNA and DNA aptamers which block therapeutically relavent proteins such as those involved in cardiovascular diseases and immune modulation.

2. To develop RNA-based tumor targeting strategies for delivering siRNAs and miRNAs to tumor cells.

3. To reprogram cells using mRNA delivery.

4. To explore novel methods to control inflammation.

Appointments and Affiliations

  • Joseph W. and Dorothy W. Beard Professor of Experimental Surgery, in the School of Medicine
  • Professor of Surgery
  • Director of the Duke Center for Translational Research
  • Professor of Pharmacology and Cancer Biology
  • Associate Professor in Molecular Genetics and Microbiology
  • Member of the Duke Cancer Institute

Contact Information:

  • Office Location: 1079 MSRB II, Box 103035, Durham, NC 27710
  • Office Phone: (919) 684-6413
  • Email Address: bruce.sullenger@duke.edu

Education:

  • Ph.D. Cornell University, 1990

Representative Publications:

    • Buddai, SK; Layzer, JM; Lu, G; Rusconi, CP; Sullenger, BA; Monroe, DM; Krishnaswamy, S, An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase., The Journal of biological chemistry, vol 285 no. 8 (2010), pp. 5212-5223 [10.1074/jbc.M109.049833] [abs].
    • Wang, J; Wakeman, TP; Lathia, JD; Hjelmeland, AB; Wang, X-F; White, RR; Rich, JN; Sullenger, BA, Notch promotes radioresistance of glioma stem cells., Stem Cells, vol 28 no. 1 (2010), pp. 17-28 [10.1002/stem.261] [abs].
    • Mi, J; Liu, Y; Rabbani, ZN; Yang, Z; Urban, JH; Sullenger, BA; Clary, BM, In vivo selection of tumor-targeting RNA motifs., Nature Chemical Biology, vol 6 no. 1 (2010), pp. 22-24 [10.1038/nchembio.277] [abs].
    • Oney, S; Lam, RTS; Bompiani, KM; Blake, CM; Quick, G; Heidel, JD; Liu, JY-C; Mack, BC; Davis, ME; Leong, KW; Sullenger, BA, Development of universal antidotes to control aptamer activity., Nature Medicine, vol 15 no. 10 (2009), pp. 1224-1228 [10.1038/nm.1990] [abs].
    • Blake, CM; Sullenger, BA; Lawrence, DA; Fortenberry, YM, Antimetastatic potential of PAI-1-specific RNA aptamers., Oligonucleotides, vol 19 no. 2 (2009), pp. 117-128 [10.1089/oli.2008.0177] [abs].
    • Long, SB; Long, MB; White, RR; Sullenger, BA, Crystal structure of an RNA aptamer bound to thrombin., RNA (New York, N.Y.), vol 14 no. 12 (2008), pp. 2504-2512 [10.1261/rna.1239308] [abs].
    • Dollins, CM; Nair, S; Boczkowski, D; Lee, J; Layzer, JM; Gilboa, E; Sullenger, BA, Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer., Chemistry & Biology, vol 15 no. 7 (2008), pp. 675-682 [10.1016/j.chembiol.2008.05.016] [abs].
    • Giangrande, PH; Zhang, J; Tanner, A; Eckhart, AD; Rempel, RE; Andrechek, ER; Layzer, JM; Keys, JR; Hagen, P-O; Nevins, JR; Koch, WJ; Sullenger, BA, Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia., Proceedings of the National Academy of Sciences of USA, vol 104 no. 32 (2007), pp. 12988-12993 [10.1073/pnas.0704754104] [abs].
    • Kierlin-Duncan, MN; Sullenger, BA, Using 5'-PTMs to repair mutant beta-globin transcripts., RNA (New York, N.Y.), vol 13 no. 8 (2007), pp. 1317-1327 [10.1261/rna.525607] [abs].
    • Nimjee, SM; Keys, JR; Pitoc, GA; Quick, G; Rusconi, CP; Sullenger, BA, A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery., Molecular Therapy, vol 14 no. 3 (2006), pp. 408-415 [10.1016/j.ymthe.2006.04.006] [abs].
    • McNamara, JO; Andrechek, ER; Wang, Y; Viles, KD; Rempel, RE; Gilboa, E; Sullenger, BA; Giangrande, PH, Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras., Nature Biotechnology, vol 24 no. 8 (2006), pp. 1005-1015 [10.1038/nbt1223] [abs].
    • Jones, JP; Kierlin, MN; Coon, RG; Perutka, J; Lambowitz, AM; Sullenger, BA, Retargeting mobile group II introns to repair mutant genes., Molecular Therapy, vol 11 no. 5 (2005), pp. 687-694 [10.1016/j.ymthe.2005.01.014] [abs].
    • Nimjee, SM; Rusconi, CP; Sullenger, BA, Aptamers: an emerging class of therapeutics., Annual Review of Medicine, vol 56 (2005), pp. 555-583 [10.1146/annurev.med.56.062904.144915] [abs].
    • Rusconi, CP; Roberts, JD; Pitoc, GA; Nimjee, SM; White, RR; Quick, G; Scardino, E; Fay, WP; Sullenger, BA, Antidote-mediated control of an anticoagulant aptamer in vivo., Nature Biotechnology, vol 22 no. 11 (2004), pp. 1423-1428 [10.1038/nbt1023] [abs].
    • Layzer, JM; McCaffrey, AP; Tanner, AK; Huang, Z; Kay, MA; Sullenger, BA, In vivo activity of nuclease-resistant siRNAs., RNA (New York, N.Y.), vol 10 no. 5 (2004), pp. 766-771 [abs].
    • Byun, J; Lan, N; Long, M; Sullenger, BA, Efficient and specific repair of sickle beta-globin RNA by trans-splicing ribozymes., RNA (New York, N.Y.), vol 9 no. 10 (2003), pp. 1254-1263 [abs].
    • White, RR; Shan, S; Rusconi, CP; Shetty, G; Dewhirst, MW; Kontos, CD; Sullenger, BA, Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2., Proceedings of the National Academy of Sciences of USA, vol 100 no. 9 (2003), pp. 5028-5033 [10.1073/pnas.0831159100] [abs].
    • Rogers, CS; Vanoye, CG; Sullenger, BA; George, AL, Functional repair of a mutant chloride channel using a trans-splicing ribozyme., Journal of Clinical Investigation, vol 110 no. 12 (2002), pp. 1783-1789 [10.1172/JCI16481] [abs].
    • Rusconi, CP; Scardino, E; Layzer, J; Pitoc, GA; Ortel, TL; Monroe, D; Sullenger, BA, RNA aptamers as reversible antagonists of coagulation factor IXa., Nature, vol 419 no. 6902 (2002), pp. 90-94 [10.1038/nature00963] [abs].
    • Sullenger, BA; Gilboa, E, Emerging clinical applications of RNA., Nature, vol 418 no. 6894 (2002), pp. 252-258 [10.1038/418252a] [abs].
    • Martell, RE; Nevins, JR; Sullenger, BA, Optimizing aptamer activity for gene therapy applications using expression cassette SELEX., Molecular Therapy, vol 6 no. 1 (2002), pp. 30-34 [abs].
    • Watanabe, T; Sullenger, BA, RNA repair: a novel approach to gene therapy., Advanced Drug Delivery Reviews, vol 44 no. 2-3 (2000), pp. 109-118 [abs].
    • Rusconi, CP; Yeh, A; Lyerly, HK; Lawson, JH; Sullenger, BA, Blocking the initiation of coagulation by RNA aptamers to factor VIIa., Thrombosis and haemostasis, vol 84 no. 5 (2000), pp. 841-848 [abs].
    • Sullenger, BA, Series introduction: emerging clinical applications of nucleic acids, Journal of Clinical Investigation, vol 106 no. 8 (2000), pp. 921-922 [10.1172/JCI11343] [abs].
    • White, RR; Sullenger, BA; Rusconi, CP, Developing aptamers into therapeutics., Journal of Clinical Investigation, vol 106 no. 8 (2000), pp. 929-934 [10.1172/JCI11325] [abs].
    • Lan, N; Rooney, BL; Lee, SW; Howrey, RP; Smith, CA; Sullenger, BA, Enhancing RNA repair efficiency by combining trans-splicing ribozymes that recognize different accessible sites on a target RNA., Molecular Therapy, vol 2 no. 3 (2000), pp. 245-255 [10.1006/mthe.2000.0125] [abs].
    • Watanabe, T; Sullenger, BA, Induction of wild-type p53 activity in human cancer cells by ribozymes that repair mutant p53 transcripts., Proceedings of the National Academy of Sciences of USA, vol 97 no. 15 (2000), pp. 8490-8494 [10.1073/pnas.150104097] [abs].
    • Long, MB; Sullenger, BA, Evaluating group I intron catalytic efficiency in mammalian cells., Molecular and Cellular Biology, vol 19 no. 10 (1999), pp. 6479-6487 [abs].
    • Sullenger, BA, RNA repair as a novel approach to genetic therapy., Gene Therapy, vol 6 no. 4 (1999), pp. 461-462 [10.1038/sj.gt.3300903] [abs].
    • Zarrinkar, PP; Sullenger, BA, Optimizing the substrate specificity of a group I intron ribozyme., Biochemistry, vol 38 no. 11 (1999), pp. 3426-3432 [10.1021/bi982688m] [abs].
    • Zarrinkar, PP; Sullenger, BA, Probing the interplay between the two steps of group I intron splicing: competition of exogenous guanosine with omega G., Biochemistry, vol 37 no. 51 (1998), pp. 18056-18063 [abs].
    • Lan, N; Howrey, RP; Lee, SW; Smith, CA; Sullenger, BA, Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors., Science, vol 280 no. 5369 (1998), pp. 1593-1596 [abs].
    • Jones, JT; Sullenger, BA, Evaluating and enhancing ribozyme reaction efficiency in mammalian cells., Nature Biotechnology, vol 15 no. 9 (1997), pp. 902-905 [10.1038/nbt0997-902] [abs].
    • Lee, SW; Sullenger, BA, Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine receptors from myasthenic antibodies., Nature Biotechnology, vol 15 no. 1 (1997), pp. 41-45 [10.1038/nbt0197-41] [abs].
    • Jones, JT; Lee, SW; Sullenger, BA, Trans-splicing reactions by ribozymes., Methods in molecular biology (Clifton, N.J.), vol 74 (1997), pp. 341-348 [10.1385/0-89603-389-9:341] [abs].
    • Ishizaki, J; Nevins, JR; Sullenger, BA, Inhibition of cell proliferation by an RNA ligand that selectively blocks E2F function., Nature Medicine, vol 2 no. 12 (1996), pp. 1386-1389 [abs].
    • Sullenger, BA, Ribozyme-mediated repair of RNAs encoding mutant tumor suppressors., Cytokines and Molecular Therapy, vol 2 no. 3 (1996), pp. 201-205 [abs].
    • Lee, SW; Sullenger, BA, Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes., The Journal of Experimental Medicine, vol 184 no. 2 (1996), pp. 315-324 [abs].
    • Jones, JT; Lee, SW; Sullenger, BA, Tagging ribozyme reaction sites to follow trans-splicing in mammalian cells., Nature Medicine, vol 2 no. 6 (1996), pp. 643-648 [abs].
    • Sullenger, BA, Colocalizing ribozymes with substrate RNAs to increase their efficacy as gene inhibitors., Applied Biochemistry and Biotechnology, vol 54 no. 1-3 (1995), pp. 57-61 [abs].
    • Sullenger, BA, Revising messages traveling along the cellular information superhighway., Chemistry & Biology, vol 2 no. 5 (1995), pp. 249-253 [abs].
    • Doudna, JA; Cech, TR; Sullenger, BA, Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor., Proceedings of the National Academy of Sciences of USA, vol 92 no. 6 (1995), pp. 2355-2359 [abs].
    • Smith, C; Sullenger, BA, AIDS and HIV infection., Molecular and cell biology of human diseases series, vol 5 (1995), pp. 195-236 [abs].
    • Campbell, TB; Sullenger, BA, Alternative approaches for the application of ribozymes as gene therapies for retroviral infections., Advances in pharmacology (San Diego, Calif.), vol 33 (1995), pp. 143-178 [abs].
    • Sullenger, BA; Cech, TR, Ribozyme-mediated repair of defective mRNA by targeted, trans-splicing., Nature, vol 371 no. 6498 (1994), pp. 619-622 [10.1038/371619a0] [abs].
    • Sullenger, BA; Cech, TR, Tethering ribozymes to a retroviral packaging signal for destruction of viral RNA., Science, vol 262 no. 5139 (1993), pp. 1566-1569 [abs].
    • Lee, TC; Sullenger, BA; Gallardo, HF; Ungers, GE; Gilboa, E, Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells., The New biologist, vol 4 no. 1 (1992), pp. 66-74 [abs].
    • Sullenger, BA; Gallardo, HF; Ungers, GE; Gilboa, E, Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation., Journal of virology, vol 65 no. 12 (1991), pp. 6811-6816 [abs].
    • Sullenger, BA; Lee, TC; Smith, CA; Ungers, GE; Gilboa, E, Expression of chimeric tRNA-driven antisense transcripts renders NIH 3T3 cells highly resistant to Moloney murine leukemia virus replication., Molecular and Cellular Biology, vol 10 no. 12 (1990), pp. 6512-6523 [abs].
    • Sullenger, BA; Gallardo, HF; Ungers, GE; Gilboa, E, Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication., Cell, vol 63 no. 3 (1990), pp. 601-608 [abs].
    • Hantzopoulos, PA; Sullenger, BA; Ungers, G; Gilboa, E, Improved gene expression upon transfer of the adenosine deaminase minigene outside the transcriptional unit of a retroviral vector., Proceedings of the National Academy of Sciences of USA, vol 86 no. 10 (1989), pp. 3519-3523 [abs].