Andrej Luptak

picture of Andrej  Luptak

Associate Professor
Pharmaceutical Sciences
Associate Professor, Chemistry
School of Physical Sciences
Member, Chao Family Comprehensive Cancer Center

Associate Professor, Molecular Biology and Biochemistry
School of Biological Sciences
Member, Institute for Genomics and Bioinformatics


Ph.D., Yale University, 2002, Biophysical Chemistry


M.S., University of Pennsylvania, 1996, Chemistry


B.A., University of Pennsylvania, 1996, Biochemistry and Biophysics

Phone: (949) 824-9132
Email: aluptak@uci.edu

University of California, Irvine
2141 Natural Sciences 2
Mail Code: 3959
Irvine, CA 92697
Research Interests
RNA biology and chemistry
URL
Academic Distinctions
1992-1996 Benjamin Franklin Scholar
2010 Pew Scholar
Appointments
Research Fellow, Massachusetts General Hospital & Harvard Medical School 2002-2007
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

Chem 230. Classical Mechanics and Electrodynamics

PharmSci/Chem 177. Medicinal Chemistry

Chem/PharmSci 223. Bio Macromolecules

Publications
Webb, CH and Lupták, A. (2018) Kinetic Parameters of Trans-scission by Extended HDV-like Ribozymes and the Prospect for the Discovery of Genomic Trans-cleaving RNAs.
Biochemistry (ASAP)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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.
 
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.
 
 
 
 
 
 
 
 
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.
Grants
NSF 1330606 Aptamers in model organisms
The John Templeton Foundation
Professional Societies
Graduate Programs
Chemical Biology

Medicinal Chemistry and Pharmacology

Cellular and Molecular Biosciences

Chemistry

Last updated
02/11/2018