Bruce Alan Sullenger

Bruce Alan Sullenger

Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery

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 Distinguished Professor of Experimental Surgery
  • Professor in Surgery
  • Director of the Duke Center for Translational Research
  • Professor of Cell Biology
  • Professor of Neurosurgery
  • Professor of Pharmacology and Cancer Biology
  • Member of the Duke Cancer Institute

Contact Information

  • Office Location: DUMC 103035, Durham, NC 27710
  • Office Phone: +1 919 684 6375
  • Email Address: bruce.sullenger@duke.edu

Education

  • Ph.D. Cornell University, 1990

Awards, Honors, and Distinctions

  • Fellow (NAI). National Academy of Inventors. 2018
  • AAAS Fellow. American Association for the Advancement of Science. 2014

Courses Taught

  • PHARM 494: Research Independent Study

In the News

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., J Biol Chem, 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., Nat Chem Biol, 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., Nat Med, 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, 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., Chem Biol, 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., Proc Natl Acad Sci U S A, 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, 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., Mol Ther, 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., Nat Biotechnol, 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., Mol Ther, 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., Annu Rev Med, 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., Nat Biotechnol, 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, vol 10 no. 5 (2004), pp. 766-771 [10.1261/rna.5239604] [abs].
  • Byun, J; Lan, N; Long, M; Sullenger, BA, Efficient and specific repair of sickle beta-globin RNA by trans-splicing ribozymes., RNA, vol 9 no. 10 (2003), pp. 1254-1263 [10.1261/rna.5450203] [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., Proc Natl Acad Sci U S A, 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., J Clin Invest, 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., Mol Ther, vol 6 no. 1 (2002), pp. 30-34 [10.1006/mthe.2002.0624] [abs].
  • Watanabe, T; Sullenger, BA, RNA repair: a novel approach to gene therapy., Adv Drug Deliv Rev, vol 44 no. 2-3 (2000), pp. 109-118 [10.1016/s0169-409x(00)00089-2] [abs].
  • Rusconi, CP; Yeh, A; Lyerly, HK; Lawson, JH; Sullenger, BA, Blocking the initiation of coagulation by RNA aptamers to factor VIIa., Thromb Haemost, vol 84 no. 5 (2000), pp. 841-848 [abs].
  • Sullenger, BA, Series introduction: emerging clinical applications of nucleic acids., J Clin Invest, vol 106 no. 8 (2000), pp. 921-922 [10.1172/JCI11343] [abs].
  • White, RR; Sullenger, BA; Rusconi, CP, Developing aptamers into therapeutics., J Clin Invest, 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., Mol Ther, 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., Proc Natl Acad Sci U S A, 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., Mol Cell Biol, vol 19 no. 10 (1999), pp. 6479-6487 [10.1128/MCB.19.10.6479] [abs].
  • Sullenger, BA, RNA repair as a novel approach to genetic therapy., Gene Ther, 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 [10.1021/bi982193x] [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 [10.1126/science.280.5369.1593] [abs].
  • Jones, JT; Sullenger, BA, Evaluating and enhancing ribozyme reaction efficiency in mammalian cells., Nat Biotechnol, vol 15 no. 9 (1997), pp. 902-905 [10.1038/nbt0997-902] [abs].
  • Jones, JT; Lee, SW; Sullenger, BA, Trans-splicing reactions by ribozymes., Methods Mol Biol, vol 74 (1997), pp. 341-348 [10.1385/0-89603-389-9:341] [abs].
  • Lee, SW; Sullenger, BA, Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine receptors from myasthenic antibodies., Nat Biotechnol, vol 15 no. 1 (1997), pp. 41-45 [10.1038/nbt0197-41] [abs].
  • Ishizaki, J; Nevins, JR; Sullenger, BA, Inhibition of cell proliferation by an RNA ligand that selectively blocks E2F function., Nat Med, vol 2 no. 12 (1996), pp. 1386-1389 [10.1038/nm1296-1386] [abs].
  • Sullenger, BA, Ribozyme-mediated repair of RNAs encoding mutant tumor suppressors., Cytokines Mol Ther, 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., J Exp Med, vol 184 no. 2 (1996), pp. 315-324 [10.1084/jem.184.2.315] [abs].
  • Jones, JT; Lee, SW; Sullenger, BA, Tagging ribozyme reaction sites to follow trans-splicing in mammalian cells., Nat Med, vol 2 no. 6 (1996), pp. 643-648 [10.1038/nm0696-643] [abs].
  • Sullenger, BA, Revising messages traveling along the cellular information superhighway., Chem Biol, vol 2 no. 5 (1995), pp. 249-253 [10.1016/1074-5521(95)90043-8] [abs].
  • Doudna, JA; Cech, TR; Sullenger, BA, Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor., Proc Natl Acad Sci U S A, vol 92 no. 6 (1995), pp. 2355-2359 [10.1073/pnas.92.6.2355] [abs].
  • Smith, C; Sullenger, BA, AIDS and HIV infection., Mol Cell Biol Hum Dis Ser, vol 5 (1995), pp. 195-236 [10.1007/978-94-011-0547-7_11] [abs].
  • Sullenger, BA, Colocalizing ribozymes with substrate RNAs to increase their efficacy as gene inhibitors., Appl Biochem Biotechnol, vol 54 no. 1-3 (1995), pp. 57-61 [10.1007/BF02787911] [abs].
  • Campbell, TB; Sullenger, BA, Alternative approaches for the application of ribozymes as gene therapies for retroviral infections., Adv Pharmacol, vol 33 (1995), pp. 143-178 [10.1016/s1054-3589(08)60668-7] [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 [10.1126/science.8248806] [abs].
  • Lee, TC; Sullenger, BA; Gallardo, HF; Ungers, GE; Gilboa, E, Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells., New Biol, 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., J Virol, vol 65 no. 12 (1991), pp. 6811-6816 [10.1128/JVI.65.12.6811-6816.1991] [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., Mol Cell Biol, vol 10 no. 12 (1990), pp. 6512-6523 [10.1128/mcb.10.12.6512-6523.1990] [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 [10.1016/0092-8674(90)90455-n] [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., Proc Natl Acad Sci U S A, vol 86 no. 10 (1989), pp. 3519-3523 [10.1073/pnas.86.10.3519] [abs].