Andrej LuptakAssociate Professor Associate Professor, Chemistry Member, Chao Family Comprehensive Cancer Center Associate Professor, Molecular Biology and Biochemistry Member, Institute for Genomics and Bioinformatics |
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Research Interests |
RNA biology and chemistry | |
| URL | Luptak Research Group Website | |
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Academic Distinctions |
1992-1996 Benjamin Franklin Scholar 2010 Pew Scholar |
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| Appointments | Research Fellow, Massachusetts General Hospital & Harvard Medical School 2002-2007 | |
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Research Abstract |
RNAs are remarkable as both information carriers and structured functional macromolecules. Beyond their well-known role in the information transfer between DNA and proteins, RNAs act as catalysts (ribozymes) in many cellular processes such as protein synthesis, splicing, and tRNA maturation. In addition, RNA can fold to form small-molecule recognition elements (riboswitches) that regulate gene expression. It is clear that RNA structure and regulation is critical to a wide variety of cellular events, but the complexity of regulatory mechanisms is only now beginning to be appreciated. This duality of function makes RNAs and their chemical analogs ideal for in vitro selection and evolution experiments. In vitro selection is a powerful tool for rapid cell-free identification of specific binders or efficient catalysts from very diverse synthetic or genomic libraries, with complexities of up to about 10E16. Aptamers, RNAs with high binding affinity and specificity, are readily isolated and can be evolved further to improve or alter their function. For example, they have been developed to bind a large variety of small molecule targets, to act as drugs that bind proteins and cells in a tissue-specific manner, and to deliver cargoes to those cells. Similarly, ribozymes have been evolved in vitro to accelerate a wide variety of chemical reactions. We explore the biology and chemistry of RNA by utilizing in vitro selection techniques and structure-based bioinformatics to search for new catalytic RNAs in a variety of genomes. Through these RNAs, we look for novel modes of cell regulation. Another way in which we combine the study of RNA biology and chemistry is to use synthetic libraries to select aptamers and ribozymes with designed characteristics. Of particular interest is the selection of fluorogenic molecules that we will use to study RNA in live cells with hitherto unprecedented spatial and temporal resolution. To facilitate the selection process we are developing novel fluorescence-based methods to display and isolate fluorogenic nucleic acids. Links to Course Web Pages |
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| Publications |
Vu, MMK, Jameson, NE, Masuda, SJ, Lin, D, Larralde-Ridaura, R & Lupták, A. (2012) Convergent evolution of adenosine aptamers spanning bacterial, human, and random sequences revealed by structure-based bioinformatics and genomic SELEX. Chemistry & Biology 19:1247-54. |
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Hammann C, Lupták A, Perreault J, de la Peña M. (2012) The uniquitous hammerhead ribozyme. RNA 18(5): 871-85. |
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| Riccitelli N, Lupták A. HDV Family of Self-Cleaving Ribozymes. Submitted. | ||
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Jimenez RM, Rampášek L, Brejová B, Vina? T, Lupták A. (2012) Discovery of RNA Motifs Using a Computational Pipeline that Allows Insertions in Paired Regions and Filtering of Candidate Sequences. Methods Mol Biol. 848:145-58. |
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Jimenez RM, Lupták A. (2012) Structure-based search and in vitro analysis of self-cleaving ribozymes. Methods Mol Biol. 848:131-43. |
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Xiao Z, Levy-Nissenbaum E, Alexis F, Lupták A, Teply BA, Chan JM, Shi J, Digga E, Cheng J, Langer R, Farokhzad OC. (2012) Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection. ACS Nano 6(1):696-704. |
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Ruminski DJ, Webb C-HT, Riccitelli NJ, Lupták A. (2011) Processing and translation initiation of non-long terminal repeat retrotransposons by hepatitis delta virus (HDV)-like self-cleaving ribozymes. J Biol Chem 286(48):41286-95. |
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Webb C-H T and Lupták A. (2011) RNA Families: HDV-like Self-cleaving Ribozymes. RNA Biology, 8(5):719-727. |
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Trevino S, Zhang N, Elenko M, Lupták A and Szostak JW. (2011) Evolution of functional nucleic acids in the presence of non-heritable backbone heterogeneity. PNAS 108(33):13492-7. |
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Iuliana E. Sendroiu, Lida K. Gifford, Andrej Lupták, and Robert M. Corn. (2011) Ultrasensitive DNA Microarray Biosensing via in Situ RNA Transcription-Based Amplification and Nanoparticle-Enhanced SPR Imaging. J Am Chem Soc, 133 (12), 4271–4273 |
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Jimenez RM, Delwart E, and Lupták A. (2011) Structure-based search reveals hammerhead ribozymes in the human microbiome. J Biol Chem 286(10):7737-43. Paper of the week. Best of JBC 2011. |
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Gifford L, Sendroiu I, Corn R, Lupták A. (2010) Attomole Detection of Mesophilic DNA Polymerase Products by Nanoparticle-Enhanced SPR Imaging on Glassified Gold Surfaces. J Am Chem Soc, 132(27): 9265-9267. |
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Riccitelli NJ, Lupták A. (2010) Computational discovery of folded RNA domains in genomes and in vitro selected libraries. Methods 52:133-140. |
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Webb C-HT, Riccitelli NJ, Ruminski DJ and Lupták A. (2009) Widespread occurrence of self-cleaving ribozymes. Science 326:953 |
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Luptak A, Szostak JW. Mammalian self-cleaving ribozymes. in Ribozymes and RNA Catalysis, eds D. Lilley and F. Eckstein, 2008. Monnard PA, Luptak A, Deamer DW. (2007) Models of primitive cellular life: polymerases and templates in liposomes. Philos Trans R Soc Lond B Biol Sci. 362(1486):1741-50. Salehi-Ashtiani K, Luptak A, Litovchick A, Szostak JW. A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. (2006) Science. 313(5794):1788-92. Luptak A, Doudna JA. Distinct sites of phosphorothioate substitution interfere with folding and splicing of the Anabaena group I intron. (2004) Nucleic Acids Res. 32(7):2272-80. Luptak A, Ferre-D'Amare AR, Zhou K, Zilm KW, Doudna JA. Direct pK(a) measurement of the active-site cytosine in a genomic hepatitis delta virus ribozyme. (2001) J Am Chem Soc. 123(35):8447-52. |
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| Grant | GM094929 Luminescent RNAs | |
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Professional Societies |
RNA Society ASBMB AAAS |
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| Graduate Programs |
Chemical Biology Medicinal Chemistry and Pharmacology Cellular and Molecular Biosciences Chemistry |
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| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=5448 | |
| Last updated | 10/25/2012 | |