个人简介

B.S., Truman State University 1995 Ph.D., University of Missouri 2001 Post doctoral fellow, University of Washington, 2001-2007

研究领域

Biochemistry

My group is interested in the atomic structures (interatomic distances, bond angles, and topology) of biomolecules associated with chromatin and chromatin modifying factors. Some of these factors generate heritable epigenetic effects that are important to biological processes such as cellular development, tumorigenesis, and aging. Recently, a number of non-coding ribonucleic acid molecules (RNAs) have been implicated in chromatin modification. We are particularly keen to study the modes of RNA recognition in these ribonucleoprotein (RNP) complexes. These RNPs are particularly exciting for the simple fact that RNA's role in epigenetic programming is still somewhat poorly understood. As a general technique, nuclear magnetic resonance spectroscopy (NMR) is appealing because it permits structure determination under physiologically relevant solution conditions, and also because it is a powerful tool for probing biophysical phenomena at the atomic level. Small molecule drug-like fragment screens and second site equilibrium binding events can be easily observed via NMR and thus nicely complement the obvious structural biology applications. Using both NMR and molecular genetics, we are investigating a number of specific factors: yeast and human telomerase RNA-protein interactions, centromeric histone variants, and RNA-polycomb protein complexes. We believe that a complete understanding of the biochemistry of RNA-protein interactions at atomic detail will be vital to understanding the biology of epigenetic change.

近期论文

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Zampino AP, Masters FM, Bladholm EL, Panzner MJ, Berry SM, Leeper TC, and Ziegler CJ “Mercury metallation of the copper protein azurin and structural insight into possible heavy metal reactivity” Journal of Inorganic Biochemistry, 141C:152-160 (2014). Chanawanno K, Caporoso J, Kondeti V, Paruchuri S, Leeper TC, Herrick RS, Ziegler CJ. “Facile solid phase peptide synthesis with a Re-lysine conjugate generated via a one-pot procedure.” Dalton Trans. 43: 11452-11455 (2014) Geldenhuys WJ, Leeper TC, Carroll RT. “mitoNEET as a novel drug target for mitochondrial dysfunction.” Drug Discovery Today. pii: S1359-6446 (2014) Bilinovich SM, Davis, CM, Morris DL, Ray LA, Prokop JW, Buchan GJ, Leeper TC. “The C-terminal domain of SRA1p has a fold more similar to PRP18 than to an RRM and does not directly bind to the SRA1 RNA STR7 region.” Journal of Molecular Biology 426:1753-1765. (2014). Herrick RS, Ziegler CJ, Leeper TC. “Structure and function in organometallic•protein complexes.” Journal of Organometallic Chemistry, 751, 90-110 (2014). Marhabaie M, Leeper TC, Blackledge TA. “Protein Composition Correlates with the Mechanical Properties of Spider ( Argiope trifasciata ) Dragline Silk.” Biomacromolecules. 15, 20-29 (2014). Wu J, Zhao C, Hu R, Lin W, Wang Q, Zhao J, Bilinovich SM, Leeper TC, Li L, Cheung HM, Chen S, Zheng J. “Probing the weak interaction of proteins with neutral and zwitterionic antifouling polymers.” Acta Biomaterialia 10, 751-760 (2014). Panzner MJ, Bilinovich SM, Parker JA, Bladholm EL, Ziegler CJ, Berry SM, Leeper TC. “Isomorphic deactivation of a Pseudomonas aeruginosa oxidoreductase: The crystal structure of Ag(I) metallated azurin at 1.7 Å.” Journal of Inorganic Biochemistry. 128, 11-16 (2013) Blackledge TA, Kuntner M, Marhabaie M, Leeper TC, Agnarsson I. “Biomaterial evolution parallels behavioral innovation in the origin of orb-like spider webs.” Scientific Reports. 2, 833 (2012). Morris MJ, Wingate KL, Silwal J, Leeper TC, Basu S. “The porphyrin TmPyP4 unfolds the extremely stable G-quadruplex in MT3-MMP mRNA and alleviates its repressive effect to enhance translation in eukaryotic cells.” Nucleic Acids Research 40, 4137–4145 (2012) Prokop JW, Leeper TC, Duan ZH, Milsted A. “Amino acid function and docking site prediction through combining disease variants, structure alignments, sequence alignments, and molecular dynamics: a study of the HMG domain.” BMC Bioinformatics. 13, Suppl 2:S3 (2012) Panzner MJ, Bilinovich SM, Youngs WJ, Leeper TC. “Silver metallation of hen egg white lysozyme: X-ray crystal structure and NMR studies.” Chemical Communications 47, 2479-81 (2011) SL Brinkley, TC Leeper, RS Rowlett, RS Herrick, CZ Ziegler, “Re(CO)3(H2O)3+ binding to lysozyme: structure and reactivity,” Metallomics 3, 909-916 (2011) TC Leeper, S Zhang, W.C Van Voorhis, PJ Myler and G Varani, “Comparative analysis of glutaredoxin domains from bacterial opportunistic pathogens.” Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 67 1141-1147 (2011) SM Bilinovich, MJ Panzner, WJ Youngs, and TC Leeper, “Poly[[{u3-2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonato}silver(I)] trihydrate],” Acta Crystallographica Section E: Structure Reports, E67, (2011) Lunde BM, Reichow SL, Kim M, Suh H, TC Leeper, Yang F, Mutschler H, Buratowski S, Meinhart A, Varani G. “Cooperative interaction of transcription termination factors with the RNA polymerase II C-terminal domain.” Nature Structural and Molecular Biology 17, 1195-1201 (2010) TC Leeper, Qu X, Lu C, Moore C, Varani G. “Novel protein-protein contacts facilitate mRNA 3'-processing signal recognition by Rna15 and Hrp1.” Journal of Molecular Biology 401, 334-349 (2010). A Davidson, TC Leeper, Z Athanassiou, K Patora-Komisarska, J Karn, JA Robinson and G Varani, “Simultaneous recognition of HIV-1 TAR RNA bulge and loop sequences by cyclic peptide mimics of Tat protein.” PNAS, 106, 11931-11936 (2009). TC Leeper, Z Athanassiou, RL Dias, JA Robinson, G Varani, “TAR RNA recognition by a cyclic peptidomimetic of Tat protein.” Biochemistry 44, 12362-12372 (2005). TC Leeper, G Varani, “The structure of an enzyme activating fragment of human telomerase RNA.” RNA 11, 394-403 (2005).