Ponzy Lu

Professor of Chemistry
Biological Chemistry

Office: 352N
Lab: 312N
Phone: 215-898-4863
Email: ponzysasupennedu

Jump to: Research Statement | Education and Academic History | Selected Publications

Research Statement
Research in Progress

In a collaboration with A. Gewirtz of the Department of Medicine, we are exploring the use of antisense molecular beacons to follow RNA transport and structure in vivo.

With Don Baldwin of the Department of Pathology and Laboratory Medicine we are developing novel approaches to the use of microarray probe technology.

Research results

Since the lac operon has been the paradigm for gene regulatory systems, our efforts have been focused on obtaining structural information on the repressor operator complex. To this end, a series of DNA binding domain fragments and variants have been cloned and expressed for solution multinuclear multidimensional NMR analysis, both as proteins and protein DNA complexes. In collaboration with M. Lewis of the Department of Biochemistry and Biophysics, the three-dimensional structures of (1) lac repressor alone, (2) lac repressor with inducer, and (3) complexes of intact tetrametic lac repressor, and operator DNA have been solved.

An interesting result from our group is the solution structure of A-tract DNA. This variation from the average B form has been studied for two decades. Several X-ray structures by other groups have been not consistent with the body of solution properties of this family of DNA sequences. Our NMR solution structure shows that the bend In the helix axis is actually 90 degrees away from the bend plane in the crystal structures. The variation of nucleic acid structures as a function of sequence and solvent conditions is an important consideration. In related experiments, we have exploited the use of fluorescence depolarization of bound ethidium bromide to investigate hydrodynamic size and shape of RNA structures, e.g., tetraloops and ribozymes. These issues have also become important as we are finding variations in mRNA accessibility to antisense probes.

Education and Academic History

Selected Publications
Arndt, K.; Nick, H.; Boschelli, F.; Lu, P.; Sadler, J., "Repressor-Operator Interaction in the Lac Operon III: NMR Observations with Altered Terminal DNA Binding Domains," J. Mol. Biol. 1982, 161, 439-457.

Cheung, S.; Arndt, K.; Lu, P., "Correlation of Lac -Operator Imino Proton Exchange Kinetics with Its Function," Proc. Natl. Acad. Sci. USA 1984, 81, 3665-3669 .

Lu, P.; Cheung, S.; Donlan, M., "A Recurrent DNA Sequence at Sites of Protein Interaction", Advances in Biophysics 1985, 20, 153-175.

Leighton, P.; Lu, P., "15N-NMR Observation of Lambda Cro Repressor with DNA", Biochemistry 1987, 26, 7262- 7271.

Metzler, W. J.; Lu, P. "Lambda Cro Repressor Complex with OR3 Operator DNA: 19F-NMR Observations", J. Mol. Biol. 1989, 205, 149- 164.

Pace, H.; Lu, P.; Lewis, M., " Lac Repressor: Crystallization of Intact Tetramer and its Complexes with Inducer and Operator DNA", Proc. Natl. Acad. Sci. 1990, 87, 1870-1873.

Rastinejad, F.; Lu, P., "T7 RNA Polymerase: 19F NMR Observations at 5-Fluorouracil Substituted Promoter DNA and RNA Transcript", J. Mol. Biol. 1993, 232, 105-122.

Rastinejad, F.; Artz,P.; Lu, P., "Origin of the Asymmetrical Contact Between Lac Repressor and Lac Operator DNA" J. Mol. Biol. 1993, 233, 389-399.

Lewis, M.; Chang, G.; Horton, N.; Kercher, M.; Pace, H.; Schumacher, M.; Breman, R.; Lu, P., "Crystal Structure of the Lactose Operon Repressor and Its Complexes with DNA and Inducer", Science 1996, 271, 1247-1254.

Duhamel, J.; Kanyo, J.; Dinter-Gottlieb, G.; Lu, P. "Fluorescene Emission of EB Intercalated in Defined DNA Duplexes: Hydrodynamics Components", Biochemistry 1996, 35, 16687-97.

Duhamel, J.; Liu, D. M.; Evilia, C.; Fleysh, N.; Dinter-Gottlieb, G.; Lu, P. "Secondary Structure of the HDV Ribozyme in 95% Formamide", Nucleic Acids Research 1996, 24, 3911-3917.

Kanyo, J.; Duhamel, J.; Lu, P., "Secondary Structure of the r(CUUCGG) Tetraloop," Nucleic Acids Research 1996, 24, 4015-4022.

Kercher, M.; Lu, P.; Lewis, M.; "Lac Repressor-Operator Complex," Current Opinion in Structural Biology 1996, 7, 76-85

Horton, N.; Lewis, M.; Lu, P.; "E. coli Lac Repressor - Lac Operator Interaction and the Influence of Allosteric Effectors," Journal of Molecular Biology 1997, 265, 1-7

Evilia, C.; Lu, P.; Zhang, X.; "A New Approach to the Synthesis of Oligodeoxynucleotides Containing 5-Fluoro-2'Deoxy-cytidine," Nucleotides and Nucleosides 1997, 16, 1809-1820

Pace, H.; Kercher, M.A.; Lu, P.; Markiewicz, P.; Miller, J.H.; Chang, G.; Lewis, M.; "Lac Repressor Genetic Map in Real Space," Trends in Biochemical Sciences 1997, 22, 334-339

Sokol, D.L.; Zhang, X.; Lu, P.;Gewirtz, A.M.; "Direct, Real Time Detection of DNA/RNA Hybridization In Vivo," Proceedings of the National Academy of Sciences of the United States of America 1998, 95, 11538-11543

MacDonald, D.; Herbert, K.; Zhang, X.; Pologruto, T.; Lu, P.; "Solution Structure of an A-Tract DNA Bend," Journal of Molecular Biology 2001, 306, 1081-1098

Rizzo, J.; Zhang, X.; Gewirtz, A.; Lu, P.; "Chimeric RNA-DNA Molecular Beacon Assay for Ribonuclease H Activity," Molecular Probes 2002, in press

MacDonald, D.; Lu, P.; "Residual Dipolar Couplings in Nucleic Acid Structure Determination," Current Opinion in Structural Biology 2002, in press