Department of Medicinal Chemistry and Molecular Pharmacology Personnel - V. Jo Davisson

V. Jo Davisson, Ph.D. Professor of Medicinal Chemistry and Molecular Pharmacology Phone: (765) 494-5238 Fax: (765) 494-1414 E-mail: davisson@purdue.edu Full directory listing

Education

Research: Molecular Design and Synthesis; Chemical and Systems Biology

Our primary interests are at the intersection of chemical and systems biology to enhance the drug discovery and development process. The research group uses both hypothesis-driven and technology-focused discovery approaches to address therapeutic strategies for unmet needs in treating several cancer diseases, emerging viral infections, and neurodegenerative diseases. We engage a number of collaborative efforts to enhance the overall approaches to addressing these objectives. Our active core research program has two overall aims:

1)           To discover and develop selective antagonists/agonists of protein assemblies. The current target systems under investigation are involved in a variety of cellular roles including DNA replication-repair, cellular vesicle transport and pH control, and viral mediated oncogenesis. The specific target systems currently under investigation include cell proliferating nuclear antigen (PCNA), the vacuolar-ATPase (v-ATPase), and the human papillomavirus virus E6 protein (HPV-E6); all are implicated in different diseases.

While our earlier research focused primarily on enzymes, all of the molecular systems under current investigation are considered non-classical or “undruggable” targets. Our efforts aim to discover and develop small molecule probes of these target systems to address their specific roles in disease contexts and serve as leads for drug discovery. A significant effort is devoted to exploring new approaches to design and discover useful chemotypes and drug leads for each of these target systems. In the process, we develop probes to test hypotheses regarding protein network interactions and define new target binding sites. Currently, biomolecular screening methods are being integrated with computational approaches and novel synthetic chemical libraries to enhance the successes of the discovery process.

A long standing interest has been to further develop understanding of molecular mechanisms of drug actions. Part of the inspiration comes from the rich biological activities of natural products and their synthetic analogs which have potential to be developed into new drug therapies. These molecular tools continue to provide rich sources for drug target discovery and/or serve as candidates for new therapeutics. We continue to pursue biochemical/proteomic and biophysical/structural biology approaches to understand and exploit the cellular pharmacology of natural products in future drug design.

2)           To develop novel high-content, quantitative, phenotypic cell-based screens for molecular discovery and evaluation which are predictive for modulation of cellular pathways and organelle functions. These collaborative efforts in platform development bridge chemical biology to bioengineering and computational sciences.

The variation of biological response to chemical effects as a function of genetic content in a biological system is a problem for integration of high content systems. Using an integrated approach of genomics, proteomics, with flow and imaging cytometry, our collaborative efforts incorporate genetic variations in disease models into cell-based screening platforms. Our efforts integrate chemical, biochemical tools with automated cytometry, spectral imaging and bioinformatics to provide innovative biological screens for pharmacodynamic-monitoring. Insights from these efforts offer understanding of how best to target susceptibilities and stage drug therapies from discovery through development.

The integration of these molecular analysis tools offer new technological interfaces that can also be applied toward clinical samples. These approaches using cell-based diagnostics when combined with molecular analysis are leading to the advancement of molecule cytomic platforms that can enhance the translation of discoveries into translational research and clinical practice. A prototype project to establish a prototype moleuclar cytomics screen for cervical cancer detection and prognosis is currently under development.

Representative Publications

Anadu, N. O., Hollingshead, M., Davisson, V. J., Cushman, M. (2006) "Synthesis and anticancer activity of brefeldin A ester derivatives" Journal of Medicinal Chemistry 49, 3897-3905.
 
Amaro, R. E., Myers, R. S., Davisson, V. J., Luthey-Schulten, Z. A. (2007) "A network of conserved interactions regulates the allosteric signal in a glutamine amidotransferase" Biochemistry 46, 2156 - 2173.
 
Schweitzer, D., Zhu, J., Jarori, G. Kane, J. J., Tanaka, J., Higa, T., Davisson, V. J. Helquist, P. (2007) "Synthesis of carbamate derivatives of iejimalides. Retention of normal antiproliferative activity and localization of binding in cancer cells" Bioorganic and Medicinal Chemistry 15, 3208-3216.
 
Loethen, Y. L., Knudsen, G. M., Davis, B., Gudihal, R., Davisson, V. J., Ben-Amotz, D. (2008) "Protein Quantitation in 2-D Gels using Fluorescence with Water Raman as an Internal Standard" Journal of Proteome Research 7, 1341-1345.
 
Rozhkov, R., Davisson, V. J., Bergstrom, D. E. (2008) "Fluorogenic Transformations Based on Formation of C-C Bonds Catalyzed by Palladium: An Efficient Approach for High Throughput Optimizations and Kinetic Studies" Advanced Synthesis and Catalysis 350, 71-75.
 
Deb, S. K., Davis, B., Knudsen, G. M., Gudihal, R., Ben-Amotz, D. Davisson, V. J. (2008) "Detection and Relative Quantification of Proteins by Surface Enhanced Raman Using Isotopic Labels" Journal of the American Chemical Society 30 9624-9625.
 
Liu, F., Hindupur, J., Nguyen, J. L., Ruf, K. J., Zhu, J., Schieler, J. L., Bonham, C. C., Wood, K. V., Davisson, V. J., Rochet, J.-L. (2008) "Methionine sulfoxide reductase A protects dopaminergic cells from Parkinson's disease-related insults" Free Radical Biology & Medicine 45 242-255.
 
Deb, S. K., Davis, B., Ben-Amotz, D., Davisson, V. J. (2008) "Accurate Concentration Measurements Using Surface-Enhanced Raman and Deuterium Exchanged Dye Pairs" Applied Spectroscopy 62, 1001-1007.
 
Knudsen, Gi., Davis, B., Deb, S., Loethen, Y., Gudihal, R., Perera, P., Ben Amotz, D., Davisson, V. J. (2008) "Quantification of Isotope Encoded Proteins in 2-D Gels Using Surface Enhanced Resonance Raman" Bioconjugate Chemistry 19, 2212-2220.