 |
FRISC: The Faculty Research Interests Science Comparator |
|
Associate Professor of Pharmacology and Biochemistry
Molecular Biophysics
Biological Chemistry
Office: (214) 648-5096
Building: Y, Room: 4.206B
Email: corey@chop.swmed.edu
Home Page: Corey Lab Home Page
The goal of our laboratory is to combine methods from both
chemistry and biology to engineer novel function into proteins and nucleic acids. We aim
to use the engineered macromolecules that we create to efficiently and selectively control
biological processes within cells - control that will allow us to directly investigate the
intricacies of cellular signaling and intracellular structure.
One project area explores the ability of oligonucleotides
to be general agents for regulating biological activity. We have developed modified
oligonucleotide chemistries that can hybridize to complementary sequences with greatly
enhanced rates. We have found that peptide nucleic acids (PNAs), an oligonucleotide motif
that possesses nonionic backbone linkages, can inhibit human telomerase and have developed
methods for introducing PNAs into human cells. Anti-telomerase PNAs introduced by this
method cause telomeres to shorten, demonstrating that we can selectively induce phenotypes
within cells. We have also shown that PNAs bind to mRNA and duplex DNA and are
investigating the ability of PNAs to be general agents for controlling gene expression.
A second project area involves investigating protease
specificity, and we have elucidated the specificities of four physiologically important
proteases, t-PA, u-PA, plasmin, and PSA. We are using this information to design
strategies for engineering new protease specificities and to gain further insights into
how protease specificity has evolved. This work has led us to appreciate the importance of
both positive and negative selection in the definition of protease specificity, and has
allowed us to target proteolysis to engineered protein substrates.
Selected Publications:
Corey D. R. (2001) Telomerase inhibition, oligonucleotides, and clinical
trials. Oncogene in Press.
Elayadi, A., Demieville, A., Wancewicz, E. V., Monia, B.P., Corey, D. R.
(2001) Inhibition of telomerase by 2'-O-(2'-methoxyethyl)RNA oligomers: Effect
of length, phosphorothioate substitution, and time inside cells. Nucl. Acids.
Res. 29: 1683-1689.
Doyle, D. F., Braasch, D. A., Boehm, M., Jackson, L., Mangelsdorf, D., and
Corey D. R. (2001) Engineering gene activation using orthogonal ligand receptor
pairs. J. Am. Chem. Soc. in Press.
Braasch, D. A. and Corey, D. R. (2001) Locked Nucleic Acids: Fine-tuning
nucleic acid recognition Chem. Biol. 8: 1-7.
Doyle D. F., Braasch, D. A, Simmons, C. G., Janowski, B. A. and Corey, D. R.
(2001) Intracellular Delivery and Inhibition of Gene Expression by Peptide
Nucleic Acids Biochemistry 40: 53-64.
Bergstrom, R. C., Mayfield, L. D and Corey D. R. (2001) A First Step into a
Protein World: Accelerating Delivery of Chemical Reactivity to DNA Chem. Biol.
8: 199-205.
Zhang, X., Ishihara, T., and Corey D. R. (2000) Strand Invasion by Mixed Base
PNAs and PNA-Peptide Chimera Nucl. Acids. Res. 28: 3332-3338.
Hervio, L., Bergstrom, R. C., Coombs, G. C., Trivedi, K., Corey, D. R. and
Madison, E. L. (2000) Negative selectivity and the evolution of protease
cascades: The specificity of plasmin for peptide and protein substrates Chem.
Biol. 7: 443-453.
Herbert, B-S., Pitts, A. E., Baker, S. I., Hamilton, S. E., Wright, W. E.,
Shay, J. W. and Corey, D. R. (1999) Inhibition of telomerase leads to eroded
telomeres, reduced proliferation, and cell death (1999) Proc. Natl. Acad. Sci.
USA 96: 14726-14781.
Hamilton, S. E., Simmons, C. G., Kathriya, I, and Corey, D. R. Cellular
delivery of peptide nucleic acids and inhibition of human telomerase (1999)
Chem. Biol. 6: 343-351.
Ishihara, T. and Corey, D. R. (1999) Rules for Strand Invasion by Chemically
Modified Oligonucleotides J. Am. Chem. Soc. 121: 2012-2020.
Mayfield, L. D. and Corey, D. R. (1999) Automated Synthesis of Peptide
Nucleic Acids (PNAs) and Peptide Nucleic Acid-Peptide Conjugates Anal.
Biochem 268: 401-404.
Pitts, A. E. and Corey, D. R. (1998) Inhibition of Human Telomerase by
2'-O-Methyl RNA Oligonucleotides Proc. Natl. Acad. Sci. 95: 11549-11554.
Coombs, G. S., Bergstrom, R. C., Pellequer, J-L., Baker, S. I., Navre, M.,
Smith, M. M., Tainer, J. A., Madison, E. L., and Corey, D. R. (1998) Substrate
Specificity of Prostate Specific Antigen (PSA) Chem. Biol., 5: 475-488.
Corey, D. R. (1997) Peptide Nucleic Acids - Expanding the options for nucleic
acid recognition Trends in Biotechnology, 15, 224-229.
Norton, J. C., Piatyszek, M. A., Wright, W. E., Shay, J. W., Corey, D. R.
(1996) Inhibition of Human Telomerase Activity by Peptide Nucleic Acids Nature
Biotech., 14: 615-620.
Corey, D. R. (1995) 48 000-fold Acceleration of Hybridization of Chemically
Modified Oligomers to Duplex DNA J. Am. Chem. Soc. 117: 9373-9374.
Page maintained by Stephanie Robertson
Last updated: 17 Jan 2002
Extraction Method: Expand using Medical Synonyms-
Eliminated words list: MedlinePlus List
-
Similarity Method: Weighted keyword count
-
Database: Medline abstracts (1967 - Present)
-
Publication Type: All
-
Score Calculation Method: Cosine Similarity Method
-
Sort by: Score
-
Show: Top 100 hits
-
Results computed on: 6/9/2006