个人简介

Robert Parry Teaching Award (2005) Camille Dreyfus Teacher Scholar (2000) NIH Postdoctoral Associate, Harvard University (1994-1996) Ph.D. Caltech (1994) Phi Beta Kappa (1989) B.S. University of North Dakota (1989)

研究领域

Chemical Biology/Organic Chemistry

The Beal laboratory of chemical biology uses synthetic chemistry and synthetic biology to study and control ribonucleic acids (RNAs). RNAs are structurally complex biopolymers whose proper function is central to all life including bacteria, viruses and humans. Our work is advancing the understanding of essential basic science principles of RNA structure and recognition and is providing a platform for the development of new medicines targeting RNA or RNA-binding proteins. We create new RNA molecules by chemical synthesis with nucleoside analogs, introducing novel and desirable features. In addition, new small molecules are synthesized that are capable of perturbing natural RNA function or the function of RNA-modifying enzymes. Finally, directed evolution carried out in our lab generates new RNA structures and new RNA-modifying enzymes with valuable properties. We have applied these approaches to the study of RNA-editing adenosine deaminases, RNA interference by short interfering RNAs (siRNAs), the RNA-dependent protein kinase (PKR), and RNA-targeted threading intercalators.

近期论文

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Kelly J. Phelps, Kiet Tran, Tristan Eifler, Anna L. Ericson, Andrew J. Fisher, and Peter A. Beal*, "Recognition of duplex RNA by the deaminase domain of the RNA editing enzyme ADAR2", Nucl. Acids. Res., 2015,(43)(1), 1123-1132. Kiet Tran, Michelle R. Arkin, and Peter A. Beal, "Tethering in RNA: An RNA-Binding Fragment Discovery Tool", Molecules, 2015,20, 4148-4161. ""Click Modification of RNA at Adenosine: Structure and Reactivity of 7-Ethynyl and 7-triazolyl-8aza-7-deazaadenosine in RNA" Kelly J Phelps, José M. Ibarra-Soza, Kiet Tran, Andrew J. Fisher, and Peter A. Beal, ACS Chem. Bio., 2014, 9(8), 1780-1787. Valenzuela, R. A. P., Suter, S. R., Ball-Jones, A. A., Ibarra-Soza, J. M., Zheng, Y. and Beal, P. A. (2014), Base Modification Strategies to Modulate Immune Stimulation by an siRNA. ChemBioChem. doi: 10.1002/cbic.201402551 "Potent and Selective Inhibition of A to I RNA Editing with 2’-O-Methyl/Locked Nucleic Acid-containing Antisense Oligoribonucleotides" Rena A. Mizrahi, Nicole T. Schirle and Peter A. Beal ACS Chem.Biol. 2013, 8, 4, 832-839. "Computational approaches to predicting the impact of novel bases on RNA structure and stability" Jason G. Harrison, Yvonne B. Zheng, Peter A. Beal and Dean J. Tantillo ACS Chem.Biol. 2013 , 8, 2354-2359. "RNA-Seq Analysis Identifies A Novel Set of Editing Substrates for Human ADAR2 Present in Saccharomyces cerevisiae" Tristan Eifler, Subhash Pokharel and Peter A. Beal Biochemistry, 2013, 52, 7857-7869. "Short Interfering RNA Guide Strand Modifiers from Computational Screening" Kazumitsu Onizuka, Jason G. Harrison, Alexi A. Ball-Jones, José M. Ibarra-Soza, Yuxuan Zheng, Diana Ly, Walter Lam, Stephanie Mac, Dean J. Tantillo and Peter A. Beal J. Am. Chem. Soc. 2013 135, 17069-17077. "A Screening Protocol for Identification of Functional Mutants of RNA Editing Adenosine Deaminases" Tristan Eifler, Dalen Chan and Peter A. Beal, Curr. Protoc. Chem. Biol., 2012, 357–369 "Promiscuous 8-Alkoxyadenosines in the Guide Strand of an siRNA: Modulation of Silencing Efficacy and Off-Pathway Protein Binding" Uday Ghanty, Erik Fostvedt, Rachel Valenzuela, Peter A. Beal and Cynthia J. Burrows, J. Am. Chem. Soc., 2012, 134 (42), 17643–17652 "7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove" José M. Ibarra-Soza, Alexi A. Morris, Prasanna Jayalath, Hayden Peacock, Wayne E. Conrad, Michael B. Donald, Mark J. Kurth and Peter A. Beal, Org. Biomol. Chem, 2012, 10, 6491-6497 "Nucleoside analog studies indicate mechanistic differences between RNA-editing adenosine deaminases" Rena A. Mizrahi, Kelly J. Phelps, Andrea Y. Ching and Peter A. Beal, Nucleic Acids Res, 2012, In Press "NEIL1 binding to DNA containing 2'-fluorothymidine glycol stereoisomers and the effect of editing" Kazumitsu Onizuka, Jongchan Yeo, Sheila S. David, and Peter A. Beal, ChemBioChem, 2012, 13, 1338-1348 "Novel Modifications in RNA" Kelly Phelps, Alexi Morris, and Peter A. Beal, ACS Chem. Biol., 2012, 7 (1), pp 100–109 "ADAR Proteins: Structure and Catalytic Mechanism" Rena A. Goodman, Mark R. Macbeth and Peter A. Beal, Curr Top Microbiol Immunol., 2012, 353; 1-33, "Chemical Modification of siRNA Bases To Probe and Enhance RNA Interference" Hayden Peacock, Arunkumar Kannan, Peter A. Beal, and Cynthia J. Burrows, J. Org. Chem., 2011, 76 (18), pp 7295-7300, "Covalent stabilization of a small molecule-RNA complex" Hayden Peacock, Radhika Bachu, and Peter A. Beal, Bioorg. Med. Chem. Lett., 2011, (21), 5002-5005, "Nucleobase and Ribose Modifications Control Immunostimulation by a MicroRNA-122-mimetic RNA" Hayden Peacock, Raymond V. Fucini, Prasanna Jayalath, Jose M. Ibarra-Soza, Henry J. Haringsma, W. Michael Flanagan, Aarron Willingham, and Peter A. Beal, J. Am. Chem. Soc., 2011, 133 (24), 9200-9203 "8-Oxoguanosine Switches Modulate the Activity of Alkylated siRNAs by Controlling Steric Effects in the Major versus Minor Grooves" Arunkumar Kannan, Erik Fostvedt, Peter A. Beal, and Cynthia J. Burrows, J. Am. Chem. Soc., 2011, 133 (16), pp 6343-6351.