Zoran Radic

Title(s)Associate Adjunct Professor, School of Pharmacy And Pharmaceutical Science
SchoolHealth Sciences
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    Collapse Biography 
    Collapse Awards and Honors
    Croatian Society of Natural Sciences2016  - 2017Spiridion Brusina Medal
    New York Academy of Science2016  - 2020Professional Member

    Collapse Overview 
    Collapse Overview
    Dr. Radic is a graduate of the University of Zagreb in Croatia where he started his research in acetylcholinesterase (AChE) reaction kinetics under mentorship of late Dr. Elsa Reiner, one of founding contributors in the field of cholinesterases. His interests in the AChE molecular structure brought him to the laboratory of Dr. Palmer Taylor at UCSD where he provided key contributions to functional mapping of the AChE molecule using site directed mutagenesis and defined structural domains and amino acid residues critical for catalytic activity and ligand interaction. He was the first to propose common, simplified kinetic scheme and equation to describe acetylcholine (ACh) turnover by both AChE and its structurally and functionally close relative butyrylcholinesterase (BChE) that included both substrate inhibition of AChE and substrate activation of BChE, two prominent forms of deviation from Michaelis-Menten kinetcs. Later this scheme and mechanism proved useful for the description of oxime reactivation kinetics of nerve agent organophosphate (OP) and OP pesticide conjugated AChE and BChE including positive allosteric modulation in reactivation of OP-BChE and negative allosteric modulation of OP-AChE conjugates. Dr. Radic developed intrinsic tryptophane fluorescence based assays as a highly valuable tool for in vitro monitoring of time resolved and equilibrium interactions of cholinergic ligands with native nicotinic acetylcholine receptor ligand binding domain surrogates, ACh binding proteins (AChBPs), as well as with AChE and BChE. This assay proved essential in functional characterization of one of tightest known, high affinity binding small molecule femtomolar AChE inhibitors developed in collaboration with Dr. Barry Sharpless of The Scripps Research Institute in La Jolla (TSRI). Dr. Radic leads, as a PI, NIH funded international collaborative project with researchers from TSRI (Dr. Barry K. Sharpless and Dr. Valery Fokin) and Institute for Medical Research and Occupational Health in Zagreb, Croatia (Dr. Zrinka Kovarik) towards development of novel, improved oxime reactivators of OP-AChE and OP-BChE conjugates, both in vitro and in vivo.

    Collapse Research 
    Collapse Research Activities and Funding
    Overlay independent X-ray data analysis for enhanced oxime OP-ChE reactivation
    NIH/NINDS R21NS098998Sep 30, 2016 - Aug 31, 2018
    Role: Principal Investigator
    Accelerated AChE Reactivator Design by Mechanistic Neutron Scattering Studies
    NIH/NINDS U01NS083451Jul 15, 2014 - Jun 30, 2019
    Role: Principal Investigator
    BChE reactivators for nerve agent and pesticide OP detoxification in human tissue
    NIH/NINDS R21NS084904Sep 30, 2013 - Aug 31, 2015
    Role: Principal Investigator
    Optimization of nonpyridinium oximes for BChE hydrolysis of OPs in plasma
    NIH/NINDS R21NS072086Sep 30, 2010 - Aug 31, 2013
    Role: Principal Investigator

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