Dr. Richard C. Willson
Professor of Chemical and Biomolecular Engineering
Professor of Biochemical & Biophysical Sciences

Dept. of Chemical and Biomolecular Engineering
University of Houston
4800 Calhoun Ave.
Houston, TX 77204-4004
Office Location: S229
Telephone: (713) 743-4308
Fax: (713) 743-4323
E-mail: My email address is my last name, at uh dot edu

EDUCATION

—B.S. Chemical Engineering, California Institute of Technology (1981; honors)
—M.S. Chemical Engineering, California Institute of Technology (1982)
—Ph.D. Chemical Engineering, Massachusetts Institute of Technology (1988)

Professional Activites

—2004-present: President, International Society for Molecular Recognition
                       (Program of 2005 and 2007 meetings)
—1999: Chair, American Chemical Society; Division of Biochemical Technology
—1999: Member/Past Chair, UH Intellectual Property Committee
—1998-present: Council on Chemical Research (CCR) Vision 2020 Roadmap committee on
                        Bioprocessing
—1995-present: Advisory, International Society for Molecular Recognition
—1988-present: Institute for Molecular Design

Editorial Boards:

— Journal of Molecular Recognition
— Journal of Biological Physics and Chemistry
— Journal of Biophysics
— Biotechnology and Applied Biochemistry
— Biotechnology Progress
— Faculty of 1000 (Structural Biology)

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HONORS

—2005 Senior Faculty Research Excellence Award, UH College of Engineering
—2001 van Lanen Award, ACS
—1999-present Fellow, American Institute of Medical and Biological Engineering
—1997-2002 Shell/UH Interdisciplinary Scholar
—1993 3M Young Faculty Award (Life Sciences Division)
—1990-1995 NSF Presidential Young Investigator
—1984-present Sigma Xi
—1983-1984 Pfizer Predoctoral Fellowship in Biochemical Engineering
—1982-1983 Shell Predoctoral Fellowship
—1981 Robert Noland Leadership Award
—1977-1981 Adolph Coors Foundation Frontiers of Science Scholarship

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RESEARCH INTERESTS

Richard Willson's laboratory works on biomolecular recognition, and its applications in separations and molecular diagnostics.

› Biomolecular recognition

We’re interested in the structural determinants of molecular recognition in complexes of proteins with recognition agents such as monoclonal antibodies and aptamers. Our primary techniques are expression, mutagenesis, fluorescence anisotropy (kinetics) and titration calorimetry. Topics of current interest include the recognition of hen egg lysozyme by a “homologous series” of antibodies differing in combining site rigidity and cross-reactivity (with S. Smith-Gill of NIH), and the biophysical chemistry of aptamer/protein recognition (with A. Ellington of UT-Austin).

› Biomolecular separations

• New chemistries for DNA/RNA purification

One example is metal-chelate affinity, also known as Immobilized Metal Affinity Chromatography, IMAC. IMAC is famous for its use in the purification of hexa-histidine tagged recombinant proteins, as well as large-scale purification of pharmaceutical proteins. We have found that the same chemistry binds purines in single-stranded RNA and DNA (which is quite useful for capturing RNA, polyA mRNA, primers, etc). We have combined the ideas of condensation conformational control and DNA metal affinity into a selective renaturation scheme in which genomic DNA is endowed with kinetically-trapped single-stranded "purification handles" that allow it to be captured by metal chelates while plasmid DNA renatures completely and does not bind. This method allows remarkable (million-fold) selectivity between plasmid (e.g., a DNA vaccine) and contaminating genomic DNA despite their chemical similarity.

• Nanostructured adsorbents

Conventional bioseparations adsorbents (e.g., ion exchangers) are derivitized with functional groups (e.g., charges), randomly distributed over their surface area. This produces a functional polyclonality or heterogeneity, in that there are some places where several charges are close together, and many where a smaller number are clustered. So the binding properties are heterogeneous, and the selectivity for purification (e.g., of protein pharmaceuticals) or analysis (e.g., proteomics) is inherently limited. We are controlling the distribution of charges on a nanometer scale by immobilizing groups of charges all at once. This reduces the heterogeneity of adsorption, and confers interesting new specificity for proteins displaying clusters of charges on their surfaces. We are now also exploring nanoclustered metal-chelates for DNA/RNA separations.

› Molecular diagnostics and sensors

• Ribosomal RNA-based identification of bacteria and viruses

One project, with UH's George Fox (co-discoverer of the Archae), is funded by NASA's National Space Biomedical Research Institute.  This project centers on the development of molecular labels and computationally-derived probes for organisms of interest to crew health in long-duration space flight. Other applications include terrestrial infectious disease diagnosis, and biodefense. The Fox lab identifies signature sequences associated with different regions of the phylogenetic tree, and we believe an array of probes to these can allow approximate classification of nearly any organism even if it has not been seen before. This last part is a substantial advance, and the work has been written up in The Scientist, Lancet Infectious Diseases, etc.

• Genome-based identification of microorganisms

As hundreds of microbial, viral, and metazoan genome sequences become available, it is increasingly possible to use this base of knowledge to design DNA probe/primer sets for organisms of interest known not to interact with background sequences (e.g., environmental background, human sequences, etc.).  This HSARPA-funded project, with George Fox and Yuriy Fofanov of UH Computer Science, relies on the remarkable computational prowess of the Fofanov group in identifying sequences of interest by exhaustive calculation. We use these results in several ways: 1. Custom DNA arrays for identification of pathogens; 2. Developing custom cocktails of RT-PCR primers rigorously known not to interact with each other, or with any human sequence or known SNP, with at least two mismatches and designed to amplify e.g., viral sequences against an overwhelming background of human DNA; 3. Engineering of hybridization-responsive fluorescent probes for these sequences. These resemble molecular beacons, but we directly incorporate environment-sensitive fluorescent nucleotide analogs such as 2-aminopurine during synthesis, etc.

• Nano- and micro-scale molecular labels

Many methods in diagnostics, genomic technology, and proteomics rely upon the sensitive detection of labels added to target or reporter molecules, to facilitate the detection of an analyte or a binding event. With Paul Ruchhoeft of UH, we are making 1-micron cubic retroreflectors (small-scale analogs of the lunar retroreflectors which are possibly the most detectable objects ever produced by mankind) for use as labels and in one-step assays based on self-assembly. With Dmitri Litvinov of UH (formerly Seagate) we are seeking to adapt the GMR technology which has radically improved data-storage hard disk drive performance, to produce a biosensor array of extremely high feature density and number (millions), capable of single-molecule detection (using 50 nm magnetic particle labels) and magnetic pull-off “melting curves” for each spot to ensure high data quality.

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SELECTED PUBLICATIONS

1. Vu, Binh; Litvinov, Dmitri; Willson, Richard; "Gold Nanoparticle Effects in PCR: Polymerase Adsorption Favors Smaller Products", Analytical Chemistry, in press.
2. Peterson, K.J., Sadowsky, J.D., Scheef, E.A., Pal, S., Kourentzi, K.D., Willson, R.C.,Bresnick, E.H., Sheibani. N. and Gellman, S., "A Fluorescence Polarization Assay for Identifying Ligands that Bind to Vascular Endothelial Growth Factor", Analytical Biochemistry, in press.
3. Jackson GW, McNichols RJ, Fox GE, Willson RC., "Toward Universal Flavivirus Identification by Mass Cataloging", J Mol Diagn. 10(2):135-141 (2008).
4. Añez M, Putonti C, Fox GE, Fofanov Y, Willson RC., "Exhaustive computational identification of pathogen sequences far-distant from background genomes: Identification and experimental verification of human-blind dengue PCR primers", J Biotechnol. 133(3):267-76 (2008).
5. Ortego BC, Whittenton JJ, Li H, Tu SC, Willson RC., "In vivo translational inaccuracy in Escherichia coli: missense reporting using extremely low activity mutants of Vibrio harveyi luciferase", Biochemistry 46(48):13864-73 (2007).
6. Fu JY, Balan S, Potty A, Nguyen V, Willson RC., "Enhanced protein affinity and selectivity of clustered-charge anion-exchange adsorbents", Anal Chem. 79(23):9060-5 (2007).
7. Larios-Sanz M, Kourentzi KD, Warmflash D, Jones J, Pierson DL, Willson RC, Fox GE., "16S rRNA beacons for bacterial monitoring during human space missions", Aviat Space Environ Med. 78(4 Suppl):A43-7 (2007).
8. Jackson GW, McNichols RJ, Fox GE, and Willson RC., "Universal bacterial identification by mass spectrometry of 16S ribosomal RNA cleavage products", International Journal of Mass Spectrometry. 2007 Mar 15; 261(2-3):218-226.
9. Tucker DL, Ott CM, Huff S, Fofanov Y, Pierson DL, Willson RC, Fox GE., "Characterization of Escherichia coli MG1655 grown in a low-shear modeled microgravity environment" BMC Microbiol. 2007 Mar 7;7(1):15.
10. Cano T, Offringa N, Willson RC., "The effectiveness of three multi-component binding models in describing the binary competitive equilibrium adsorption of two cytochrome b(5) mutants", J Chromatogr A. 2007 Mar 16;1144(2):197-202.
11. Svitel J, Boukari H, Van Ryk D, Willson RC, Schuck P., "Probing the functional heterogeneity of surface binding sites by analysis of experimental binding traces and the effect of mass transport limitation", Biophys J. 2007 Mar 1;92(5):1742-58.
12. Jackson GW, McNichols RJ, Fox GE, Willson RC., "Bacterial genotyping by 16S rRNA mass cataloging.", BMC Bioinformatics. 2006 Jun 23;7:321.
13. Fu JY, Potty AS, Fox GE, Willson RC., "Water-elutability of nucleic acids from metal-chelate affinity adsorbents: enhancement by control of surface charge density.", J Mol Recognit. 2006 Jul-Aug;19(4):348-53
14. Potty AS, Fu JY, Balan S, Haymore BL, Hill DJ, Fox GE, Willson RC., "Neutral additives enhance the metal-chelate affinity adsorption of nucleic acids: role of water activity.", J Chromatogr A. 2006 May 19;1115(1-2):88-92.
15. Murphy JC, Cano T, Fox GE, Willson RC., "Compaction agent protection of nucleic acids during mechanical lysis.", Biotechnol Prog. 2006 Mar-Apr;22(2):519-22.
16. Zhang Z, Jackson GW, Fox GE, Willson RC., "Microbial identification by mass cataloging.", BMC Bioinformatics. 2006 Mar 8;7:117.
17. Putonti C, Chumakov S, Mitra R, Fox GE, Willson RC, and Fofanov Y., "Human-blind probes and primers for dengue virus identification",  FEBS J. 273(2):398-408 (2006).
18. Cano T, Murphy JC, Fox GE, & Willson R.C., "Separation of Genomic DNA from Plasmid DNA by selective renaturation with IMAC capture", Biotechnology Progress 21: 1472-1477 (2005).
19. Jackson GW, and Willson R, "Preparative electrophoresis with on-column optical fiber monitoring and direct elution into a minimized volume", Biotechnol Lett. 27(22):1739-43 (2005).
20. Cano T, Offringa ND, and Willson RC, "Competitive ion-exchange adsorption of proteins: isotherms with controlled competitor concentration", J Chromatogr A. 24;1079(1-2):116-26 (2005).
21. Chumakov, S., Belapurkar, C., Putonti, C., Li, T.-B., Pettitt, B.M., Fox, G.E., Willson, R.C. and Fofanov, Y. Theoretical Basis for Universal Identification Systems for Bacteria and Viruses. Journal of Biological Physics and Chemistry. 5(4); 121-128 (2005).
22. Mulder BA, Anaya S, Yu P, Lee KW, Nguyen A, Murphy J, Willson R, Briggs JM, Gao X, and Hardin SH, "Nucleotide modification at the gamma-phosphate leads to the improved fidelity of HIV-1 reverse transcriptase", Nucleic Acids Res. 33(15):4865-73 (2005).
23. Tucker DL, Karouia F, Wang J, Luo Y, Li TB, Willson RC, Fofanov Y, and Fox GE, "Effect of an artificial RNA marker on gene expression in Escherichia coli", Appl Environ Microbiol. 71(7):4156-9 (2005).
24. Jandhyala DM, Willson RC, Sewell BT, and Benedik MJ.  "Comparison of cyanide-degrading nitrilases", Appl Microbiol Biotechnol. 68(3):327-35 (2005).
25. Cohen, G.H., Silverton, E.W., Padlan, E.A., Dyda, F.,  Wibbenmeyer, J.A., Willson, R.C., and Davies, D.R. (2005).  "Water molecules in the antibody-antigen interface of the structure of the Fab HyHEL-5-lysozyme complex at 1.7  Å resolution: comparison with results from isothermal titration calorimetry", Acta Crystallographica Section D: Biological Crystallography, D61, 628-633.
26. Forsman, Z.H., Lednicky, J.A., Fox, G.E., Willson, R.C., White, Z.S., Halvorson, S.J., Wong, C., Lewis, A.M. Jr, and Butel, J.S., "Phylogenetic analysis of polyomavirus simian virus 40 from monkeys and humans reveals genetic variation.", Journal of Virology, 78(17):9306-16 (2004).
27. Gibbs, P.R., Riddle, R.R., Marchal, M., Benedik, M.J. and Willson, R.C., "Purification and characterization of 2'aminobiphenyl-2,3-diol 1,2-dioxygenase from Pseudomonas sp. LD2" , Protein Expression and Purification 32:35-43 (2003).
28. Jandhyala, D., Berman, M., Meyers, P.R., Sewell, B.T., Willson, R.C., and Benedik, M.J.,  "CynD, the Cyanide Dihydratase from Bacillus pumilus: Gene Cloning and Structural Studies", Applied and Environmental Microbiology, 69:4794-4805 (2003).
29. Kourentzi, K.D., George E. Fox, G.E. and Willson. R.C.,"Hybridization-responsive fluorescent DNA probes containing the adenine analog 2-aminopurine", Analytical Biochemistry, 322(1), 124-126 (2003).
30. Gibbs, P.R., Uehara, C.S., Nguyen, P.T., and Willson, R.C., "Imaging Polarimetry for High Throughput Chiral Screening", Biotechnology Progress, 19(4); 1329-1334 (2003).
31. Murphy, J. C., Jewell, D. L., White, K. I., Fox, G. E., and Willson, R. C., "Nucleic Acid Separations Utilizing Immobilized Metal Affinity Chromatography", Biotechnology Progress, 19: 982-986 (2003).
32. DeWalt, B., Murphy, J. C., Fox, G. E., and Willson, R. C., "Compaction Agent Clarification of Microbial Lysates", Protein Expression and Purification, 28(2) 220 – 223 (2003).
33. Balan, S. E., Murphy, J. C., Galaev, I., Kumar, A., Fox, G. E., Mattiasson, B., and Willson, R. C., "Metal Chelate Affinity Precipitation of Nucleic Acids", Biotechnology Letters 25:1111-1116 (2003).
34. D'Souza, L.M., Larios-Sanz, M.,  Setterquist, R. A., Willson, R. C., and Fox, G. E.  "Small RNA Sequences are readily stabilized by inclusion in a carrier rRNA", Biotechnology Progress, 19: 734-738 (2003).
35. Riddle, R. R., Gibbs, P. R., Willson, R.C., and  Benedik, M. J."Recombinant carbazole-degrading strains for enhanced petroleum processing", J. Ind. Microbiol. Biotechnol. 30: 6-12 (2003).
36. Riddle, R., P.R. Gibbs, R.C. Willson and M.J. Benedik, "Purification and Properties of 2-hydroxy-6-oxo-6-(2'-aminophenyl)hexa-2,4-dienoic acid Hydrolase Involved with Microbial Degradation of Carbazole". Protein Expression and Purification. 28:182-189 (2003).
37. Murphy J.C., Fox G.E., and Willson, R.C. "Enhancement of anion-exchange chromatography of DNA using compaction agents",  J. Chromatogr. A. 984: 215-21 (2003).
38. Shick, K.A., S. Mohan, S.J. Smith-Gill and R.C. Willson, "Calorimetric Study of Monoclonal Antibody HyHEL-10 Association with Hen and Japanese Quail-Egg Lysozymes," Biochimica et Biophysica Acta (in press, 2002).
39. Murphy, J.C., G.E. Fox and R.C. Willson, "Compaction Agents Enhance Anion-Exchange Adsorption of Nucleic Acids," Journal of Chromatography, (in press, 2002).
40. Kourentzi, K.D., G.E. Fox and R.C. Willson, "Microbial Detection with Low-Molecular-Weight RNA," Current Microbiology, 43(6), 444-447 (2001).
41. Kourentzi, K.D., G.E. Fox and R.C. Willson, "Microbial Identification by Immunohybridization Assay of Artificial RNA Labels," J. Microbiol. Methods, 49(3), 301-306 (2002).
42. Zhang, Z., R.C. Willson and G.E. Fox, "Identification of Characteristic Oligonucleotides in the 16S Ribosomal RNA Sequence Dataset," Bioinformatics, 18, 244-250 (2002).
43. Kourentzi, K.D., G.E. Fox and R.C. Willson, "Rapid Identification of Microorganisms using 5S rRNA Specific Molecular Beacons," Current Microbiology, 43, 444 (2001).
44. Murphy, J.C., G.E. Fox and R.C. Willson, "RNA Isolation and Fractionation using Compaction Agents," Analytical Biochemistry, 295, 143 (2001).
45. D'Souza, L.M., R.C. Willson and G.E. Fox, "Expression of Marker RNAs in Pseudomonas Putida," Current Microbiology, 40, 91-95 (2000).
46. K.A. Xavier, S.M. McDonald, J.A. McCammon, and R.C. Willson. "Association and dissociation kinetics of Bobwhite quail lysozyme with monoclonal antibody HyHEL-5", Protein Engineering, 12(1), 79-83 (1999).
47. Wibbenmeyer, J.A., Xavier, K.A., Smith-Gill, S.J. and Willson, R.C. "Cloning, Expression, and Characterization of the Fab Fragment of the Anti-Lysozyme Antibody HyHEL-5", BBA 1430, 191-202 (1999).
48. Singh, N. and Willson, R.C., "Boronate affinity adsorption of RNA: possible role of conformational changes", Journal of Chromatography, 840, 205-213 (1999).
49. Riddle, R.R., Willson, R.C., and Benedik, M.J., "Temperature- and solvent-tolerant mutants of filamentous bacteriophage helper M13 KO7", Biotechnology Letters, 21 (1):87-90, 1999.
50. Li, H., Ortego, B.C., Maillard, K.I., Willson, R.C., and Tu, S.-C., "Effects of mutations of the alpha His-45 residue of Vibrio harveyi luciferase on the yield and reactivity of flavin peroxide intermediate", Biochemistry, 38(14), 4409-4415 (1999).
51. Murphy, J.C., Wibbenmeyer, J.A., Fox, G.E. and Willson, R.C., "Purification of plasmid DNA using selective precipitation by compaction agents", Nature Biotechnology, 17, 822, 1999.
52. Wibbenmeyer, J.A., P. Schuck, S.J. Smith-Gill, and R.C. Willson, "Salt Links Dominate Affinity of Antibody HyHEL-5 for Lysozyme Through Enthalpic Contributions," Journal of Biological Chemistry, 274(38), 26838-42 (1999).
53. Xavier, K.A., Shick, K.A., and Willson, R.C., "Association and Dissociation kinetics of anti-hen egg lysozyme monoclonal antibodies HyHEL-5 and HyHEL-10", Biophys. J. 74, 2036-2045 (1998).
54. Benedik, M.J., Gibbs, P.R., Riddle, R.R., and Willson, R.C., "Microbial denitrogenation of fossil fuels", Trends Biotechnol. 16, 390-395 (1998).
55. Shick, K.A., Xavier, K.A., Rajpal, A., Smith-Gill, S.J. and Willson, R.C., "Association of the anti-hen egg lysozyme monoclonal antibody HyHEL-5 with avian species variant and mutant lysozymes", Biochim. Biophys. Acta 1340, 205-214 (1997).
56. Xavier, K.A., Shick, K.A., Smith-Gill, S.J. and Willson, R.C., "Involvement of water molecules in the association of monoclonal antibody HyHEL-5 with Bobwhite quail lysozyme", Biophys. J. 73, 2116-2125 (1997).
57. Maillard, K.I., Benedik, M.J. and Willson, R.C., "Rapid detection of mutagens by induction of luciferase-bearing prophages in E. coli", Environmental Science and Technology, 30(8), 2478-2483 (1996).
58. Chacko, S., Silverton, E.W., Smith-Gill, S.J., Davies, D.R., Shick, K.A., Xavier, K.A., Willson, R.C., Jeffrey, P.D., Chang, C.Y.Y., Sieker, L.C., and Sheriff, S., "Refined structures of Bobwhite quail lysozyme uncomplexed and complexed with the HyHEL-5 Fab fragment", Proteins: Structure, Function, and Genetics 26, 55-65 (1996).
59. Moates, F.C., Somani, M., Annamalai, J., Richardson, J.T, Luss, D. and Willson, R.C., "Infrared Thermographic Screening of Combinatorial Libraries of Heterogeneous Catalysts", Industrial and Engineering Chemistry Research, 35(12), 4801-4803 (1996).

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