Bruce Alan Sullenger, PhD

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Professor of Surgery
Professor of Pharmacology and Cancer Biology
Associate Professor in Molecular Genetics and Microbiology
Director of the Duke Center for Translational Research
Department / Division:
Surgery / Surgical Sciences
Address:
1087 Msrb Ii
Box 103035
Durham, NC 27710
Office Telephone:
(919) 684-6413
Training:
  • PhD, Cornell University, 1990
Research Interests:
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.
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. Journal of Biological Chemistry. 2010;285:5212-5223.  Abstract
  • 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. 2010;6:22-24.  Abstract
  • Wang, J; Wakeman, TP; Lathia, JD; Hjelmeland, AB; Wang, XF; White, RR; Rich, JN; Sullenger, BA. Notch promotes radioresistance of glioma stem cells. Stem Cells. 2010;28:17-28.  Abstract
  • Blake, CM; Sullenger, BA; Lawrence, DA; Fortenberry, YM. Antimetastatic potential of PAI-1-specific RNA aptamers. Oligonucleotides. 2009;19:117-128.  Abstract
  • Oney, S; Lam, RT; Bompiani, KM; Blake, CM; Quick, G; Heidel, JD; Liu, JY; Mack, BC; Davis, ME; Leong, KW; Sullenger, BA. Development of universal antidotes to control aptamer activity. Nature Medicine. 2009;15:1224-1228.  Abstract
  • 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 and Biology. 2008;15:675-682.  Abstract
  • Long, SB; Long, MB; White, RR; Sullenger, BA. Crystal structure of an RNA aptamer bound to thrombin. RNA. 2008;14:2504-2512.  Abstract
  • Giangrande, PH; Zhang, J; Tanner, A; Eckhart, AD; Rempel, RE; Andrechek, ER; Layzer, JM; Keys, JR; Hagen, PO; 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. 2007;104:12988-12993.  Abstract
  • Kierlin-Duncan, MN; Sullenger, BA. Using 5'-PTMs to repair mutant beta-globin transcripts. RNA. 2007;13:1317-1327.  Abstract
  • 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. 2006;24:1005-1015.  Abstract
  • 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. 2006;14:408-415.  Abstract
  • Jones, JP; Kierlin, MN; Coon, RG; Perutka, J; Lambowitz, AM; Sullenger, BA. Retargeting mobile group II introns to repair mutant genes. Molecular Therapy. 2005;11:687-694.  Abstract
  • Nimjee, SM; Rusconi, CP; Sullenger, BA. Aptamers: an emerging class of therapeutics. Annual Review of Medicine. 2005;56:555-583.  Abstract
  • Layzer, JM; McCaffrey, AP; Tanner, AK; Huang, Z; Kay, MA; Sullenger, BA. In vivo activity of nuclease-resistant siRNAs. RNA. 2004;10:766-771.  Abstract
  • 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. 2004;22:1423-1428.  Abstract
  • Byun, J; Lan, N; Long, M; Sullenger, BA. Efficient and specific repair of sickle beta-globin RNA by trans-splicing ribozymes. RNA. 2003;9:1254-1263.  Abstract
  • 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. 2003;100:5028-5033.  Abstract
  • Martell, RE; Nevins, JR; Sullenger, BA. Optimizing aptamer activity for gene therapy applications using expression cassette SELEX. Molecular Therapy. 2002;6:30-34.  Abstract
  • Rogers, CS; Vanoye, CG; Sullenger, BA; George, AL. Functional repair of a mutant chloride channel using a trans-splicing ribozyme. Journal of Clinical Investigation. 2002;110:1783-1789.  Abstract
  • Rusconi, CP; Scardino, E; Layzer, J; Pitoc, GA; Ortel, TL; Monroe, D; Sullenger, BA. RNA aptamers as reversible antagonists of coagulation factor IXa. Nature. 2002;419:90-94.  Abstract
  • Sullenger, BA; Gilboa, E. Emerging clinical applications of RNA. Nature. 2002;418:252-258.  Abstract
  • 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. 2000;2:245-255.  Abstract
  • Rusconi, CP; Yeh, A; Lyerly, HK; Lawson, JH; Sullenger, BA. Blocking the initiation of coagulation by RNA aptamers to factor VIIa. Thrombosis and Haemostasis. 2000;84:841-848.  Abstract
  • Sullenger, BA. Series introduction: emerging clinical applications of nucleic acids. Journal of Clinical Investigation. 2000;106:921-922.  Abstract
  • 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. 2000;97:8490-8494.  Abstract
  • Watanabe, T; Sullenger, BA. RNA repair: a novel approach to gene therapy. Advanced Drug Delivery Reviews. 2000;44:109-118.  Abstract
  • White, RR; Sullenger, BA; Rusconi, CP. Developing aptamers into therapeutics. Journal of Clinical Investigation. 2000;106:929-934.  Abstract
  • Long, MB; Sullenger, BA. Evaluating group I intron catalytic efficiency in mammalian cells. Molecular and Cellular Biology. 1999;19:6479-6487.  Abstract
  • Sullenger, BA. RNA repair as a novel approach to genetic therapy. Gene Therapy (Basingstoke). 1999;6:461-462.  Abstract
  • Zarrinkar, PP; Sullenger, BA. Optimizing the substrate specificity of a group I intron ribozyme. Biochemistry. 1999;38:3426-3432.  Abstract
  • Lan, N; Howrey, RP; Lee, SW; Smith, CA; Sullenger, BA. Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors. Science. 1998;280:1593-1596.  Abstract
  • Zarrinkar, PP; Sullenger, BA. Probing the interplay between the two steps of group I intron splicing: competition of exogenous guanosine with omega G. Biochemistry. 1998;37:18056-18063.  Abstract
  • Jones, JT; Lee, SW; Sullenger, BA. Trans-splicing reactions by ribozymes. Methods in Molecular Biology. 1997;74:341-348.  Abstract
  • Jones, JT; Sullenger, BA. Evaluating and enhancing ribozyme reaction efficiency in mammalian cells. Nature Biotechnology. 1997;15:902-905.  Abstract
  • Lee, SW; Sullenger, BA. Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine receptors from myasthenic antibodies. Nature Biotechnology. 1997;15:41-45.  Abstract
  • Ishizaki, J; Nevins, JR; Sullenger, BA. Inhibition of cell proliferation by an RNA ligand that selectively blocks E2F function. Nature Medicine. 1996;2:1386-1389.  Abstract
  • Jones, JT; Lee, SW; Sullenger, BA. Tagging ribozyme reaction sites to follow trans-splicing in mammalian cells. Nature Medicine. 1996;2:643-648.  Abstract
  • Lee, SW; Sullenger, BA. Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes. Journal of Experimental Medicine. 1996;184:315-324.  Abstract
  • Sullenger, BA. Ribozyme-mediated repair of RNAs encoding mutant tumor suppressors. Cytokines and Molecular Therapy. 1996;2:201-205.  Abstract
  • Campbell, TB; Sullenger, BA. Alternative approaches for the application of ribozymes as gene therapies for retroviral infections. Advances in Pharmacology. 1995;33:143-178.  Abstract
  • 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. 1995;92:2355-2359.  Abstract
  • Smith, C; Sullenger, BA. AIDS and HIV infection. Molecular and cell biology of human diseases series. 1995;5:195-236.  Abstract
  • Sullenger, BA. Colocalizing ribozymes with substrate RNAs to increase their efficacy as gene inhibitors. Applied Biochemistry and Biotechnology. 1995;54:57-61.  Abstract
  • Sullenger, BA. Revising messages traveling along the cellular information superhighway. Chemistry and Biology. 1995;2:249-253.  Abstract
  • Sullenger, BA; Cech, TR. Ribozyme-mediated repair of defective mRNA by targeted, trans-splicing. Nature. 1994;371:619-622.  Abstract
  • Sullenger, BA; Cech, TR. Tethering ribozymes to a retroviral packaging signal for destruction of viral RNA. Science. 1993;262:1566-1569.  Abstract
  • 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. 1992;4:66-74.  Abstract
  • 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. 1991;65:6811-6816.  Abstract
  • Sullenger, BA; Gallardo, HF; Ungers, GE; Gilboa, E. Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell. 1990;63:601-608.  Abstract
  • 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. 1990;10:6512-6523.  Abstract
  • 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. 1989;86:3519-3523.  Abstract