V. Jo Davisson

Photo
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 general interests are at the intersection of chemical and 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.

Historically, Dr. Davisson's research has covered a broad range of experimental approaches ranging from mechansim-based drug design to analytical instrument testing and development. He has formal graduate education and training in organic chemistry and biochemistry and has been called a pioneer in the now maturing arena of chemical biology. His interdisciplinary efforts continue to guide and motivate the current research program. His continued efforts to develop interdisciplinary education and training environments is represented by his long standing commitments to the mission of the academic unit. 

The current research themes in general terms can be stated as:

  • Chemical probes & medicinal chemistry for antivirals, anticancer, neurodegeneration
  • Drugging non-conventional protein targets
  • New modalities for drug development-beyond the rule of 5 molecules

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

Lia I. (Cori) Boese (Graduate Student)
Naoaki Fujii (Principal Research Scholar)
Jonathon Gast (Graduate Student)
Nivedita S Mahajani (Post-Doctoral Research Associate)
Vallabh Suresh (Post-Doctoral Research Associate)
Chinnarajesh Ummadisetti (Post-Doctoral Research Associate)

Interests

Drug discovery and design technologies 

  • Chemical probes & medicinal chemistry for antivirals, anticancer, neurodegeneration
  • Drugging non-conventional protein targets
  • New modalities for drug development-beyond the rule of 5 molecules

Diseases:

  • Cancers: breast cancers, pancreatic cancer, HPV-associated cancers 
  • Emerging infectious agents: coronavirus, ebola virus, dengue virus.
  • Degenerative diseases: ALS, Parkinsons, Alzheimer's, chronic kidney disease

Technology commercialization

  • new chemcial agents for molecular detection in clinical diagnostics
  • new molecular entities as antiviral therapeutics
  • molecularly targeted adjuvant agents for cancer therapies 

Promoting entrepreneurship

Undergraduates in academic research

Service and Engagement

ACS Medicinal Chemistry Division Long Range Planning 2017-2019

NIH Review panels

Founder and Chief Scientific Officer of Amplified Sciences

Teaching

MCMP 570 Basic Principles of Chemical Action on Biological Systems

PHRM 460 Drug Discovery and Development I

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

2018                            Teacher of the Year Award for BS Pharmaceutical Sciences

Administration and Committee Work

2019-2020

B.S. Pharmaceutical Sciences Oversight Committee: Chair

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

Sips PY, Shi X, Musso G, Nath AK, Zhao Y, Nielson J, Morningstar J, Kelly AE, Mikell B, Buys E, Bebarta V, Rutter J, Davisson VJ, Mahon S, Brenner M, Boss GR, Peterson RT, Gerszten RE, MacRae CA. (2018) “Identification of specific metabolic pathways as druggable targets regulating the sensitivity to cyanide poisoning.” Plos One 13 (6):e0193889. doi: 10.1371/journal.pone.0193889. PMID:29879736

Ali R, Brown W, Purdy SC, Davisson VJ, Wendt MK. (2018) “Biased Signaling Downstream of Epidermal Growth Factor Receptor Regulates Proliferative versus Apoptotic Response to Ligand” Cell Death Dis. 9 (10):976. doi: 10.1038/s41419-018-1034-7. PMID:30250119

Lindstrom A, Anantpadma M, Baker L, Raghavendra NM, Davey R, Davisson VJ. (2018) “Phenotypic Prioritization of Diphyllin Derivatives That Block Filoviral Cell Entry by Vacuolar (H+)-ATPase Inhibition.” ChemMedChem. 13 (24):2664-2676. doi: 10.1002/cmdc.201800587. PMID:30335906

Bartolowits, M. D., Xin, M., Petrov, D., Tague, T., Davisson, V. J. (2019) “Multimeric Rhodamine Dye-Induced Aggregation of Silver Nanoparticles for Surface-Enhanced Raman Scattering” ACS Omega 4 (1) 140-145. doi:10.1021/acsomega.8b02970. PMID: 30729221

Morningstar J, Lee J, Hendry-Hofer T, Witeof A, Lyle LT, Knipp G, MacRae CA, Boss GR, Peterson RT, Davisson VJ, Gerszten RE, Bebarta VS, Mahon S, Brenner M, Nath AK. (2019) “Intramuscular administration of hexachloroplatinate reverses cyanide-induced metabolic derangements and counteracts severe cyanide poisoning.” FASEB Bioadv. 2019 Feb;1(2):81-92. doi: 10.1096/fba.1024. Epub 2018 Oct 8. PMID: 31355359

Bartolowits M. D., Gast J. M., Hasler A. J., Cirrincione A. M., O'Connor R. J., Mahmoud A. H., Lill M. A., Davisson V. J. (2019) “Discovery of Inhibitors for Proliferating Cell Nuclear Antigen Using a Computational-Based Linked-Multiple-Fragment Screen.” ACS Omega Sep 6;4(12):15181-15196. doi: 10.1021/acsomega.9b02079. eCollection 2019 Sep 17 PMID: 31552364

 


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