Department of Medicinal Chemistry and Molecular Pharmacology Personnel - V. Jo Davisson
Specialization: Molecular Design and Synthesis; Chemical and Systems Biology
EducationB.A. - 1978 - Wittenberg University
M.S. - 1983 - Indiana University School of Medicine
Ph.D. - 1988 - University of Utah
Postdoc - 1988-89 - University of California, San Francisco
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 can be stated in 3 broad 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) 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.
2) To harness chemical scaffolds and mechanisms of action for natural product drugs. 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. The current efforts use ligand-based drug design approaches to discover new and improved modulators for isoforms of the vacuolar-ATPase (v-ATPase). In particular, we are developing drugs for a variety of applications as antivirals or anti-metastatic activities.
3) 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.
Lab Members:Matthew David (Matt) Bartolowits (Post-Doctoral Research Assistant)
Jonathon Gast (Graduate Student)
Aaron Raymond Lindstrom (Graduate Student)
Dino P. Petrov (Graduate Student)
Andres Felipe Salazar (Visiting Scholar)
Drug discovery and design technologies
Diseases: breast cancers, HPV-associated cancers, pancreatic cancer, ebola virus, dengue virus
Undergraduates in research
MCMP 570 Basic Principles of Chemical Action on Biological Systems
MCMP 690 Systems Biology in Drug Discovery and Pharmacology
PHRM 460 Drug Discovery and Development I
MCMP 618 Molecular Targets: Cancer
Honors and Credentials
1978 American Institute of Chemists Undergraduate Award
1986 University of Utah Graduate Student Research Prize
1989 Damon Runyon-Walter Winchell Fellowship
1999 Purdue University Scholar
2004 Walther Cancer Institute Research Prize
2007 Purdue Cancer Center Lions Club Award
2012 Fellow of American Association for Advancement of Science
2014 Chaney Research Scholar Award
Administration and Committee Work
Current: BS Pharmaceutical Sciences Committee
Jeffrey D. Altenburg, Andrew A. Bieberich, Colin Terry, Kevin A. Harvey, Justin F. VanHorn, Zhidong Xu, V Jo Davisson and Rafat A. Siddiqui (2011) “A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone” BMC Cancer 11, 149.
Qingshou Chen, Dirk Schweitzer, John Kane, V. Jo Davisson, and Paul Helquist (2011) “Total synthesis of iejimalide B” J. Org. Chem., 76, 5157–5169.
Mout, R., Xu, Z-D., Wolf, A., Davisson, V.J., Jarori, G.K. (2012) “Anti-malarial activity of geldanamycin derivatives in mice infected with Plasmodium yoelii” Malaria Journal 11: 54
Robinson, J.P., Rajwa, B., Patsekin, V., Davisson, V. J. (2012) “Computational analysis of high-throughput flow cytometry data” Exp Opin Drug Discovery 7 (8) 679-693.
Tsiper, M. V., Sturgis, J., Avramova, L. V., Parakh, S., Fatig, R., Juan-García, A., Li, N., Rajwa, B., Narayanan, P., Qualls, Jr., C. W., Robinson, J. P., Davisson, V. J. (2012) “Differential Mitochondrial Toxicity Screening and Multi-parametric Data Analysis” PlosOne 7 (10) e45226
D'Ordine RL, Linger RS, Thai CJ, Davisson V. J. “Catalytic zinc site and mechanism of the metalloenzyme PR-AMP cyclohydrolase.” (2012) Biochemistry 51(29):5791-803.
Han, B., Wright, R., Kirchhoff, A. M., Chester, J. A., Cooper, B. R., Davisson, V. J., Barker, E. (2013) "Quantitative LC-MS/MS analysis of arachidonoyl amino acids in mouse brain with treatment of FAAH inhibitor" Anal. Biochem. 432 (2):74-81.
Robinson, J. P., Holdman, C., Ragheb, K., Sturgis, J., Fatig, R., Avaramova, L. V., Rajwa, B., Davisson, V. J., Lewis, N., Narayanan, P., Li, N., Qualls Jr., C. W. (2013) “High-Throughput Secondary Screening at the Single-Cell Level” J. Lab Automation (1):85-98.
Oliver, J. S., Linger, R. S., Chittur, S. V., Davisson, V. J. “Substrate Activation and Conformational Dynamics of Guanosine 5′-Monophosphate Synthetase” (2013) Biochemistry, 52, 5225−5235
Siddiqui R. A., Harvey K. A., Xu Z., Natarajan S. K., Davisson V. J. (2014) “Characterization of lovastatin-docosahexaenoate anticancer properties against breast cancer cells” Bioorg Med Chem. 22(6):1899-908. doi: 10.1016/j.bmc.2014.01.051 PMID: 24556504
Oliver J. C., Gudihal R., Burgner J. W., Pedley A. M., Zwierko A. T., Davisson V. J., Linger R. S. (2014) “Conformational changes involving ammonia tunnel formation and allosteric control in GMP synthetase” Arch Biochem Biophys. 545:22-32. doi: 10.1016/j.abb.2014.01.004. PMID: 24434004
Pedley, A. M., Lill, M. A., Davisson, V. J. (2014) “Flexibility of PCNA-Protein Interface Accommodates Differential Binding Partners” PlosOne e102481. doi: 10.1371/journal.pone.0102481 PMID:25036435.
Bartolowits M, Davisson V. J. (2015) “Considerations of Protein Subpockets in Fragment-Based Drug Design” Chem Biol Drug Des. Jan;87(1):5-20. doi: 10.1111/cbdd.12631. Epub 2015 Aug 31. PMID: 26307335
Rietz A., Petrov D. P., Bartolowits M., DeSmet M., Davisson V. J., Androphy E. J. (2016) Molecular Probing of the HPV-16 E6 Protein Alpha Helix Binding Groove with Small Molecule Inhibitors. PLoS One :e0149845. doi: 10.1371/journal.pone.0149845. PMID: 26915086
All publications for V. Jo Davisson (an Adobe Acrobat file)
This record was last updated on Feb 26, 2016 at 12:44 PM