Arthur Pardi

Office: JSCBB B223
Lab: JSCBB B250
Lab Phone: 303-492-8085
Fax: 303-492-5894


Ph.D.: University of California at Berkeley, 1980
Postdoctoral Fellow: NATO Fellow, 1982-83

Areas of Expertise

Molecular Biophysics, Nucleic Acids, Structural Biology, Biophysics

Awards and Honors

Henry Rutgers Research Fellow, 1985-1987Searle Scholar, 1985-1988Johnson & Johnson Discovery Research Award 1987NIH Research Career Development Award 1991-1996NIH Career Merit Award 1999 – 2010Faculty Fellowship Award, University of Colorado, 2002-2003College Scholar Award, University of Colorado, 2010

Structure-Function of RNAs and Proteins

Professor Pardi's primary research interests are in the area of biophysical chemistry and NMR spectroscopy. High-resolution multi-dimensional NMR experiments are used to probe the structure and dynamics of biomolecules in solution. The Pardi group also continues to develop improved methods for determining the solution structures of proteins and RNAs. A long-range goal is to understand the relationship between the structures (and dynamics) of these molecules and their biological functions.

Systems currently being studied in the lab include the hammerhead self-cleaving catalytic and a therapeutic RNA aptamer, Macugen, that binds with extremely high affinity to the angiogenic regulatory protein VEGF.  This aptamer is currently used in the treatment of age-related macular degeneration. Structural and biochemical studies are being performed on other RNA and DNA aptamers that bind with high affinity and specificity to the angiogenic regulatory protein VEGF.  The goal here is to better understand the molecular mechanism by which these aptamers recognized their target protein with such high affinity and specificity.  A variety of biophysical methods are used to probe the structure and dynamics of RNAs and proteins.  For example ensemble and single molecule fluorescence resonance energy transfer techniques are being used to follow global folding of the hammerhead ribozyme, to better understand the catalytic mechanism of this ribozyme.

We also have collaborations with several other groups in the Department.  For example, NMR is being used to study the structures of proteins involved in assembly of the outer membranes in gram-negative bacteria with Professor Sousas's group. Studies of protein dynamics are being used to help design brighter and more photostable red fluorescent proteins in collaboration with Professors Palmer and R. Jimenez and in collaboration with Professor Ahn, NMR spectroscopy is being used to understand how protein dynamics affect the catalytic activity of the MAP kinase, ERK2.

Lee, J. H., Canny, M. D., De Erkenez, A., Krilleke, D., Ng, Y. S., Shima, D. T., Pardi, A. & Jucker, F. (2005). A therapeutic aptamer inhibits angiogenesis by specifically targeting the heparin binding domain of VEGF(165). Proc. Natl. Acad. Sci. U. S. A. 102, 18902-18907.

Downey, C. D., Fiore, J. L., Stoddard, C. D., Hodak, J. H., Nesbitt, D. J. & Pardi, A. (2006). Metal Ion Dependence, Thermodynamics, and Kinetics for Intramolecular Docking of a GAAA Tetraloop and Receptor Connected by a Flexible Linker. Biochemistry 45, 3664-73.

Latham, M. P. & Pardi, A. (2009). Measurement of imino H-1-H-1 residual dipolar couplings in RNA. J. Biomol. NMR 43, 121-129.

Latham, M. P., Zimmermann, G. R. & Pardi, A. (2009). NMR Chemical Exchange as a Probe for Ligand-Binding Kinetics in a Theophylline-Binding RNA Aptamer. J. Am. Chem. Soc. 131, 5052-5053.

Warner, L. R., Varga, K., Lange, O. F., Baker, S. L., Baker, D., Sousa, M. C. & Pardi, A. (2011). Structure of the BamC Two-Domain Protein Obtained by Rosetta with a Limited NMR Data Set. J. Mol. Biol. 411, 83-95.