V. Jo Davisson

Professor of Medicinal Chemistry and Molecular Pharmacology
Phone:
765-494-5238
Fax:
765-494-1414
Specialization: Medicinal Chemistry and Chemical-Systems Biology

Education

B.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

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 and 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 of natural product drugs. A long standing interest has been to further develop an 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 pharmacodynamics and drug target engagement. Insights from these efforts offer an understanding of how best to target susceptibilities and stage drug therapies from discovery through development.

Lab Members

Jonathon Gast (Graduate Student)
Aaron Raymond Lindstrom (Graduate Student)
Dino P. Petrov (Graduate Student)

Interests

Drug discovery and design technologies

Diseases: breast cancers, HPV-associated cancers, pancreatic cancer, ebola virus, dengue virus. autism spectrum disorders, ALS, chronic kidney disease

Undergraduates in research

Technology commercialization

Promoting entrepreneurs

Service and Engagement

ACS Medicinal Chemistry Division Long Range Planning 2017-present

Teaching

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

2017

B.S. Pharmaceutical Sciences Oversight Committee: Chair

Purdue University Graduate Council

Purdue Undergraduate Curriculum Council

MCMP Graduate Advisory Committee 

Representative Publications

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

Thomas F.M., Goode K.M., Rajwa B., Bieberich A.A., Avramova L.V., Hazbun T.R., Davisson V.J. (2017) “A Chemogenomic Screening Platform Used to Identify Chemotypes Perturbing HSP90 Pathway” SLAS Discov. Jul;22(6):706-719. doi: 10.1177/2472555216687525. Epub 2017 Jan 31. PMID:28346089

Goode K.M., Petrov D.P., Vickman R.E., Crist S.A., Pascuzzi P.E., Ratliff T.L., Davisson V.J., Hazbun T.R. (2017) “Targeting the Hsp90 C-terminal domain to induce allosteric inhibition and selective client downregulation” Biochim Biophys Acta. Aug;1861(8):1992-2006. doi: 10.1016/j.bbagen.2017.05.006. Epub 2017 May 8. PMID:2849520

Bartolowits M.D., Brown W., Ali R., Pedley A.M., Chen Q., Harvey K.E., Wendt M.K., Davisson V.J. (2017) “Selective Inhibition of STAT3 Phosphorylation Using a Nuclear-targeted Kinase Inhibitor” ACS Chem Biol. 2017 Aug 8. doi: 10.1021/acschembio.7b00341. [Epub ahead of print] PMID:28787571


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