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 History and Research Interests

The objectives of the group are to understand the role of lipid oxidation in disease, to develop new diagnostic tools for identifying individuals at risk and assessing the efficacy of therapeutic interventions, and to provide a molecular basis for the design of new drugs and strategies for the prevention or treatment of oxidative injury. 

Dr. Salomon did undergraduate studies at the University of Chicago, graduate and postdoctoral studies at the University of Wisconsin, and further postdoctoral studies at Indiana University.  In 1973 he joined the faculty of Case Western Reserve University where he is the Charles Fredrick Mabery Professor of Research in Chemistry.

The group's research, built on a foundation of physical and synthetic organic chemistry, bridges chemistry, biology, and medicine.   Previous accomplishments and continuing interest focus on the biologically important chemistry of lipids.
  • Discovery of naturally occurring molecules and their biologically important chemistry guided by prior total synthesis of targets identified by mechanistic considerations
    • This unconventional approach was especially effective for the discoveries of levuglandins and isolevuglandins, oxidized lipids that are so extraordinarily reactive that isolating them from biological sources has not been possible.
  • Mechanistic elucidation of lipid oxidative pathways and the reactions of oxidized lipids with biological nucleophiles such as proteins and DNA
    • The reactions of oxidized lipids, such as levuglandins, with proteins and DNA are often toxic events that may contribute to disease processes.
  • Investigation of the influences of biological environments such as membranes and lipoprotein particles, on lipid oxidation and the chemistry of oxidized lipids
    • Compartmentalization and the lipophilic-hydrophilic dichotomy are pervasive characteristics of biological systems.
  • Detection and structural characterization of disease-related lipid-based oxidative modifications of proteins with immunological, mass spectroscopic, and chromatographic tools
    • The exquisite sensitivity and structural selectivity of antibodies are well-suited for detecting posttranslational lipid-based modifications of proteins in biological systems, such as retina.
    • Mass spectroscopic techniques provide an abundance of structural information that allows microscale characterization of the protein targets of lipid-based oxidative modification.
  • Clinical investigation of the involvement of lipid oxidation in disease, such as atherosclerosis
    • Protein adducts of certain lipid oxidation products, e. g., isolevuglandins, provide a dosimeter for oxidative stress that is more closely correlated with cardiovascular disease than are classical risk factors, e. g., total serum cholesterol or LDL cholesterol levels.
    • Protein-bound carboxyethylpyrroles (CEPs) are docosahexaenoate-derived oxidative modifications that are grossly elevated in the retinas of individuals with age-related macular degeneration and in melanoma.
  • Design, synthesis, and evaluation of new medicinal agents
    • Lipophilic histidine-containing nucleophiles that intercept and detoxify electrophilic lipid oxidation products are potentially useful competitive inhibitors of lipid-based oxidative protein modification. Such an antielectrophile defense may complement the well-known antioxidant defenses.
    • Lipophilic analogues are potentially useful inhibitors of receptor-mediated, e.g., CD-36, cellular resopnses to certain oxidized phospholipids.

 Facilities, Resources, and Environment

The Lipid Research Group is based in the Millis Science Center.  The laboratory is named after its distinguished former occupant, George A. Olah, winner of the 1994 Nobel Prize in Chemistry.  An HPLC area has UV, fluorescence, refractive index, and evaporative light scattering detectors.  A hot room for radiochemical experiments has both stand-alone and flow-through (for HPLC) liquid scintillation counters.  Two cell culture rooms, one for bacteria and one for mammalian cells, are equipped with laminar flow hoods, incubators, centrifuges, a thermocycler, microscope, electrophoresis, and cryostorage equipment. The Lipid Research laboratories are well equipped for immunological studies (multiwell plate scanner, incubators), organic synthesis, tissue and cell fractionation (ultracentrifuge), and kinetics (temperature controlled UV-visible).  Shared departmental instrumentation is extensive.

Strong collaborative interactions with biomedical researchers in the CWRU School of Medicine and at the Cleveland Clinic Foundation provide opportunities for students in the group to perform sophisticated mass spectroscopic (LC-MS, MALDI-TOF, Q-TOF), cell culture, and animal studies, and to conduct clinical investigations on human subjects.

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