Organic and Bioconjugate Chemistry, Radiopharmaceutical Development, Radiotracer synthesis, Structure-Activity Relationships, Medicinal Chemistry, Boron analysis in plants
Ph.D., North Carolina State University, 1981
B.S.H.E., University of Delaware, 1974
Post-Doctoral Fellowship, The Johns Hopkins University, 1981-1982
Research Associate, Department of Environmental Health Sciences,
The Johns Hopkins University School of Hygiene and Public Health, 1982-1985
Assistant Professor, Department of Environmental Health Sciences,
The Johns Hopkins University School of Hygiene and Public Health, 1985-1991
Associate Professor, Department of Environmental Health Sciences,
The Johns Hopkins University School of Hygiene and Public Health, 1991-2000
Director, Functional Imaging Laboratory, Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, 1999-2000
Associate Professor; Department of Chemistry, University of Missouri-Columbia, 2000-present
Scientist; MU Research Reactor, University of Missouri-Columbia, 2000-present
Recent Honors and Awards:
2015 "Lee Henson Mizzou Access Award," awarded by the Chancellors Committee on Persons with Disabilities, a campus award
2013 “Excellence in Education” Awardee, an MU Campus Award
2012 The Molecular Imaging and Contrast Agent Database (of the National Institutes of Health) added one of our diagnostic imaging compounds, [125I](E)-N-1-(3’-iodoallyl)-N’-4-(3’’, 4’’-dimethoxyphenyl)-piperazine “[125I]E-1.” Document created by Liang Shan August 16, 2012
2010 Honorary Coach for the Mizzou Gymnastics program
2010 The Molecular Imaging and Contrast Agent Database (of the National Institutes of Health) added one of our diagnostic imaging compounds, “[111In]Bomproamide.” Document created by Arvind Chopra May 20, 2010
2007 – 2010 Temporary Member, National Institutes of Health - National Cancer Institute: Radiation Therapeutics and Biology Study Section, Oncological Sciences Integrated Review Group
2007 – present NEXUS (a minority science network) Advisory Committee
2007 – 2010 Personnel Committee of the Chemistry Department (elected position)
2006 “Purple Chalk Award” for Excellence in Teaching in the College of Arts and Science
2005 Honorary Coach, MU Women’s Soccer Team
2005 Wakonse Fellow
2005 Who's Who Among America's Teachers ®, 2004-2005 (student nomination)
My research utilizes synthetic organic chemistry, radiochemistry and nuclear chemistry to learn more about the human brain with diagnostic imaging tracers, treating cancer with radiotherapeutic constructs and plants with analytical and tracer techniques. Currently, within the diagnostic imaging arena, we have developed a novel radioiodinated tracer that has good pharmacokinetics and selectivity to bind sigma 1 receptors in vivo. This novel tracer can monitor the binding of cocaine to the sigma 1 receptor in mice at pharmacologically relevant doses. My collaborators and I are interested in the development of anti-cocaine medications using this approach. Furthermore, we synthesize novel compounds that are evaluated for their affinity and selectivity to the sigma receptor subtypes, receptors that are implicated in a number of psychiatric diseases and cancer.
Radioligands for Sigma-2 receptor Studies in the CNS by PET
While sigma-2 (σ2) receptors play a role in anxiety, depression, movement disorders and psychostimulant abuse, these important aspects of their CNS pharmacology remain relatively unexplored. In part, this is a consequence of the lack of radioligands for in vivo studies of σ2 receptors in animal models and for non-invasive brain PET imaging. We are exploring the synthesis novel Fluorine-18 (18F) radioligands that will display high σ2 receptor affinity and selectivity. Because of the longer half-life of 18F (110 minutes), there is great potential for identifying leading candidates to be used in brain PET imaging of σ2 receptors in human beings.
Radiotracers to study the effects of stress and drought on plants
A new avenue of research concerns the translation of the radiopharmaceutical paradigm into plant biology. As part of the recently (August, 2014) NSF-funded Arkansas-Missouri Consortium “Plant Stress Response Through Innovations in Phenomics and Molecular Imaging Technologies,” studies are directed toward the synthesis of Carbon-11 labeled precursors to ascorbic acid. Because Carbon-11 has a short half-life (20 minutes), Carbon-13 and Carbon-14 labeled compounds will also be used to model reactions and analyses.
Boron’s role in plant development
A new avenue of research, to develop a better understanding of the role Boron plays in plant reproduction, is a collaborative effort with Dr. Paula McSteen of Biological Sciences. A critical step in this process is to determine the location and concentration of boron in normal and mutant maize at high spatial resolution. Unfortunately, boron does not have any radioactive isotopes; thus, the radiotracer principle cannot be applied. However, 10B, which comprises about 20% of natural boron, has a very large nuclear cross-section and can participate in a reaction initiated by a neutron beam at the MU Research Reactor (MURR) (10B + n à 7Li + 4He). We are using this approach, termed neutron capture radiography, to provide information at high spatial resolution. We are also using LA-ICP-MS and ICP-MS as complementary techniques.
Wang X, Brockman JD, Guthrie JM, Lever SZ (2018). Analysis and imaging of boron distribution in maize by quantitative neutron capture radiography. Appl Radiat Isot 2018;140:252-261.
Lever SZ, Fan K-H, Lever JR. Tactics for pre-clinical validation of receptor-binding radiotracers, Nucl Med Biol 2017;44:4-30. (invited).
Lever JR, Miller DK, Lever SZ. Chapter 49: “Cocaine Occupancy of Sigma Receptors” in: “The Neuroscience Of Cocaine: Mechanisms And Treatment,” 1st Ed. Preedy VR, Ed., London, UK: Elsevier, May 2017, p. 491-499. (invited).
Miller DK, Park ES, Lever SZ, Lever JR. N-phenylpropyl-N´-substituted piperazines occupy sigma receptors and alter methamphetamine-induced hyperactivity in mice. Pharmacology, Biochemistry and Behavior, 2016;150-151:198-206.
Lever JR, Fergason-Cantrell EA, Watkinson LD, Carmack TL, Miller DK, Lever SZ. Cocaine occupancy of sigma1 receptors and transporters in mice. Synapse 2016;70:98-111.
Xu R, Lord SA, Peterson RM, Fergason-Cantrell EA, Lever JR, Lever SZ. Ether modifications to 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503): effects on binding affinity and selectivity for sigma receptors and monoamine transporter. Bioorg Med Chem 2015; 23:220-230.
Wang X, Brockman J, Guthrie J, Durback A, Ladd R, Robertson JD, McSteen P, Lever SZ. Neutron Capture Radiography (NCR) of boron distribution in maize. Presented at the 248th American Chemical Society National Meeting, August 10-14, 2014, San Francisco, CA.
Lever JR, Miller DK, Fergason-Cantrell EA, Green CL, Watkinson LD, Carmack TL, Lever SZ. Relationship between cerebral sigma-1 receptor occupancy and attenuation of cocaine’s motor stimulatory effects in mice by PD14418. J. Pharmacol. Exp. Ther. ePub August 6, 2014; doi:10.1124/jpet.114.216671
Brust P, Deuther-Conrad W, Becker G, Patt M, Donat CK, Stittsworth S, Fischer S, Hiller A, Wenzel B, Dukic-Stefanovic S, Hess S, Steinback J, Wünsch B, Lever SZ, Sabri O. Distinctive in vivo kinetics of the new sigma1 receptor ligands (R)-(+)- and (S)-(-)-18F-Fluspidine in porcine brain. J. Nucl. Med. ePub July 28, 2014; doi: 10.2967/jnumed.114.137562
Lever JR, Miller DK, Green CL, Fergason-Cantrell EA, Watkinson LD, Carmack TL, Fan K-H, Lever SZ. A selective sigma-2 receptor ligand antagonizes cocaine-induced hyperlocomotion in mice. Synapse. 2014; 68:73-84.
Sage AS, Oelrichs CE, Davis DC, Fan K-H, Nahas RI, Lever SZ, Lever JR, Miller DK. Effects of N-phenylpropyl-N´-substituted piperazine sigma receptor ligands on cocaine-induced hyperactivity in mice. Pharmacol., Biochem. Behav. 2013; 110:201-207.
Lever SZ, Xu R, Fan K-H, Fergason-Cantrell EA, Carmack TL, Watkinson LD, Lever JR. Synthesis, radioiodination and in vitro and in vivo sigma receptor studies of N-1-allyl-N´-4-phenethylpiperazine analogs. Nucl. Med. Biol. 2012; 39:401 – 414. PMID: 22172395.
Xu R, Watkinson LD, Carmack TL, Lever JR, Lever SZ. Synthesis, Sigma Receptor Binding Studies, and in vivo Evaluation of Radioiodinated (Z)- and (E)-iodoallyl Analogs of SA4503. Med. Chem. 2012; 2:131-136.
Fan K-H, Lever JR, Lever SZ. Effect of structural modification in the amine portion of substituted aminobutyl-benzamides as ligands for binding σ1 and σ2 receptors, Bioorg. Med. Chem. 19: 1852-1859. 2011.
Akgun Z, Engelbrecht H, Fan K-H, Barnes CL, Cutler CS, Jurisson SS, Lever SZ. The complexation of rhodium(III) with acyclic diaminedithioether (DADTE) ligands. Dalton Trans. 39:10169-10178, 2010.
Abd-Elgaliel WR, Gallazzi F, Garrison J, Rold T, Sieckman G, Daibes Figueroa S, Hoffman TJ, Lever SZ. Design, Synthesis and Biological Evaluation of a Radiolabelled Antagonist-Bombesin Analog as Targeting Vector. Bioconjugate Chem. 19:2040-2048, 2008.