Josef Vagner, PhD

Associate Research Professor
Director, Ligand Discovery Laboratory
Research Associate Professor, Pharmacology
Email Address: 
Phone Number: 
(520) 626-4179

UACC Information

UACC Organizational Unit(s): 
Professional Bio: 

Dr. Vagner's research expertise is in the area of design and development of compounds for in vivo pharmacologic applications and drug discovery. He has a background in organic and medicinal chemistry, with specific training in solid phase synthesis and small molecule drug discovery.  This 25+ years of expertise also includes structural analysis and design of de novo ligands for various biological targets including a recent focus on multivalent ligand sand drug-ligand conjugates. Dr. Vagner's research career began in the pharmaceutical industry (Sanofi, Novo Nordisk, and SIDCCO) where he specialized in combinatorial chemistry and solid phase synthesis of small molecule libraries. During his time in the industry, he supervised teams of workers who successfully accomplished the synthesis of more than ten large libraries (with 10,000+ compounds each). During the last decade, as a director of the Ligand Discovery Laboratory at the University of Arizona BIO5 Institute, Dr. Vagner was responsible for design, synthesis, purification, characterization of compound libraries for multiple biological targets and their primary screening. Their center is based on collaboration attitude rather than as a core synthetic facility. His role in projects fluctuates from consultant to PI commitment that depends on a structure of assignment.

Research Information

Research Program: 
Cancer Imaging
Research Focus: 

Currently, I am leading the Ligand Discovery Lab (LDL) at Bio5, University of Arizona. The current research projects deal with the development of ligands, inhibitors, and diagnostic probes in collaboration with the UACC, UNMCC, TGen, Department of Radiology and Department of Biochemistry.

The Ligand Discovery Laboratory (LDL) is a complex chemistry center supporting investigators with libraries of chemical compounds and provides their screening.
The primary objective of the LDL is the design, synthesis, purification, characterization and screening of arrays of unique compounds for drug discovery. The LDL uses the following technologies:
  • Solid-phase synthesis (small organic compounds, biopolymers)
  • High throughput synthesis (96-well plates)
  • One-bead-one-compound (OBOC) library synthesis
  • Rational design of small molecule ligands, multimeric ligands, peptidomimetics
  • Lanthanide-based time-resolved fluorometry in vivo binding assay
  • In vivo cell-adhesion-to-bead assay for OBOC library
  • HT synthesis of labeled probes (fluorescent, DOTA-Eu)
  • Logistics and QC
Lead structures can undergo multiple development cycles. At each cycle, we will look for improvement in binding affinity, selectivity, physico-chemical properties (solubility, stability), and suitability for imaging, which is the most important parameter. Structural, analytical and storage data are entered into a database (ChemOffice, CambridgeSoft) which is compliant with the Molecular Libraries and Imaging Initiative (MLII) database.
Selected Publications: 

Dr. Vagner's NCBI bibliography

  1. Vagner, J., Barany, G., Lam, K.S., Krchnak, V., Sepetov, N.F., Ostrem, J.A., Strop, P., and Lebl, M., Enzyme-mediated spatial segregation on individual polymeric support beads: application to generation and screening of encoded combinatorial libraries. Proceedings of the National Acadademy of Science of the U.S.A., 93, 8194-8199 (1996).
  2. Cowell, S.M.; Gu, X.; Vagner, J.; Hruby, V.J. Intelligent design in combinatorial chemistry: use of designed peptide libraries to explore secondary and tertiary structures in peptides and proteins. Methods in Enzymology, 369 (Combinatorial Chemistry, Part B), 288-297 (2003).
  3. Handl, H.L.; Vagner, J.; Han, H.; Mash, E.; Hruby, V.J.; Gillies, R.J.  Hitting multiple targets with multimeric ligands. Expert Opinion on Therapeutic Targets, 8, 565-586 (2004).
  4. Vagner, J., Handl, H., Gillies, R.J., Hruby, V.J. Novel strategy based on multimeric ligands for drug delivery and imaging: homooligomers of a-MSH. Bioorganic & Medicinal Chemistry Lett. ,14, 211-215 (2004).
  5. Handl, H.L., Vagner, J., Yamamura H.I., Hruby, V.J., Gillies, R.J. Lanthanide-based time-resolved fluorescence of in cyto ligand-receptor interactions. Analytical Biochemistry, 330, 242-250 (2004).
  6. Vagner, J., Handl, H.L., Monguchi, Y., Jana, U., Begay, L., Mash, E. A., Hruby, V.J., Gillies, R.J. Rigid linkers for bioactive peptides. Bioconjugate Chemistry, 17,1545-1550 (2006).
  7. Mayorov, A.V. Cai, M. Palmer, E.S., Dedek, M.M., Cain, J.P., Van Scoy, A.P., Tan, B. Vagner, J., Trivedi, D., Hruby, V.J., Structure-Activity Relationships of Cyclic Lactam Analogues of a-MSH. Targeting the Human Melanocortin-3 Receptor.Journal of Medicinal Chemistry 51, 187-195 (2008).
  8. Vagner J., Xu L., Handl H.L., Josan J.S., Morse D.L., Mash E.A., Gillies R.J., and Hruby V.J., Heterobivalent Ligands Crosslink Multiple Cell-Surface Receptors: The Human Melanocortin-4 and d-Opioid Receptors. Angewandte Chemie Intl. Ed. 47, 1685-1688 (2008).
  9. Black, K.C., Kirkpatrick, N.D., Troutman, T.S., Xu, L., Vagner, J., Gillies, R.J., Barton, J.K., Utzinger, U., Romanowski, M. Gold nanorods targeted to delta opioid receptor: plasmon-resonant contrast and photothermal agents. Molecular Imaging 7, 50-57 (2008).
  10. Vagner, J., Qu, H., Hruby, V.J.  Peptidomimetics, a synthetic tool of drug discovery. Current Opinion in Chemical Biology 12(3), 292-296 (2008).
Collaborative Research: 

The LDL proram relies on an existing information flow from TGen, and collaborations with other groups:

Victor J Hruby (UA,pancreatic cancer, melanoma),
Gene Mash (UA,pancreatic cancer, melanoma),
Bob Gillies (Moffitt, pancreatic/breast cancer and melanoma),
Bill Monfort (UA, angiogenesis),
Ron Lynch (UA, diabetes),
Sean Limesand (UA, diabetes),
Anne Cress (UACC, prostate cancer),
Art Gmitro (Dept. of Radiology, esophagus cancer),
Scott Boitano (Bio5, astma),
Marilyn Halonen (UA, astma) ,
Michael Daines (UA, astma),
Jeff Walker (UA, cardiovascular),
Marty Pagel (UA, MRI).
5R01 GM102575-04   (Price/Dussor, MPI)                                                                             04/01/13 -02/28/17
AMPK Activators as a Novel Therapeutic for Post-surgical Pain
The goal of this research project is to gain a preclinical rationale for the further development of AMPK activators as potential therapeutics for the treatment and prevention of chronic post-surgical pain. The work focuses on AMPK and its control of plasticity-induced translation as well as possible interactions between AMPK and voltage gated channels like Nav1.7.
Role: Co-Investigator
5R01 NS073664-05    (Boitano/Vagner, MPI)                                                            09/01/11 – 07/31/16
PAR-2 Targeted Drug Discovery for the Treatment of Pain
The objective of this grant is to develop molecular ligands of PAR-2
Role: PI
5R21 CA185684-02                (Matsunaga, PI)                                                                                  04/01/14-03/30/16
Phase-Change Contrast Agents for Ultrasound Detection of Breast Cancer
The objective of this project is to develop targeted phase-change contrast agents using low boiling perfluorocarbons for delivery into the intracellular matrix of breast tumor cells.
Role: Co-Investigator
ADA 1-13-BS-117        (Lynch, PI)                                                                                                       03/01/13–06/30/16
American Diabetes Association
Multivalent GLP-1 Analogs for Beta-Cell Targeting and Therapy
The objective of this grant is to develop multivalent ligands GLP-1 with various ligands to receptors targeting pancreatic b-cells for imaging and therapeutic purposes.
Role: Co-Investigator

Professional Information

Positions and Honors: 
2008-Present   Comprehensive Member, The Arizona Cancer Center, University of Arizona, AZ
2006-Present   Member, Advanced Research Institute for Biomedical Imaging, University of Arizona, AZ
2005-Present   Associate Research Professor, Bio5, University of Arizona, AZ
2005-Present   Director of The Ligand Discovery Laboratory, Bio5, University of Arizona, AZ
2002-2005      Assistant Research Professor, Bio5, University of Arizona, AZ
1998-2001      Synthetic Organic Chemist/Principal Scientist, SIDDCO, Tucson, AZ
1995-1998      Research Chemist, Novo Nordisk A/S, Copenhagen, Denmark
1992-1995      Postdoctoral Fellow, Department of Chemistry, University of Minnesota, MN and Selectide (now Sanofi), Tucson, AZ
1990-1992      Research Chemist, Institute of Sera and Vaccines, Prague, Czech Republic
1986-1990      Research Chemist, Leciva Pharmaceuticals, Prague, Czech Republic
2006                GI SPORE, Arizona Cancer Center, Carrer Development Award
1993                Selectide (Sanofi), Postdoctoral Fellowship
Other Experience and Professional Memberships/Affiliations: 
The American Chemical Society
The American Peptide Society
The Society of Combinatorial Sciences

Academic Information

Pharm, Chemistry, Institute of Pharmacology & Biochemistry, Prague, Czech Republic
Master's Degree: 
Organic Chemistry, The Institute of Technology, Prague, Czech Republic
Undergraduate School: 
Organic Chemistry, The Institute of Technology, Prague, Czech Republic