Department of Pharmacology & Chemical Biology at the University of Pittsburgh
Rafael Radi, MD
Adjunct Professor
Departamento de Bioquímica. Facultad de Medicina, Universidad de la República.
General Flores 2125, Montevideo, 11800, PA Uruguay

Email:
rradi@ fmed.edu.uy
Phone: 598 2 924 9561

Fax: 598 2 924 9563


Education
MD - Universidad de la República, Facultad de Medicina, 1988.
PhD - Universidad de la República, Facultad de Medicina, 1991.
Photo of Rafael Radi, MD

Dr. Radi´s research activities focus on the production, chemical biology, cell signaling actions and pathological effects of oxidants and free radicals (transient reactive species produced biologically and which participate in disease processes). He has made seminal observations regarding the mechanisms of the pathogenic actions of nitric oxide. In the early nineties his discoveries revealed the mechanisms underlying the cytotoxic actions of nitric oxide and peroxynitrite. Since then, Radi´s findings related to the chemical biology, physical biochemistry, mitochondriology, cell biology and pharmacology of nitric oxide and peroxynitrite have revealed fundamental insight into the actions of reactive oxygen species, nitric oxide and peroxynitrite in cell metabolic dysfunction, apoptotic signaling, lipid oxidation/nitration and post-translational protein modification. These events in turn have relevance to disease processes where inflammation plays a critical role, including atherogenesis, hypertension and neurodegeneration.


Dr. Radi's lab has pioneered the concept that oxygen radicals serve to “shift” the physiological signaling actions of nitric oxide towards the pathophysiological. In response to this new insight, he has participated in the development, testing and chemical characterization of synthetic antioxidant molecules that serve as peroxynitrite decomposition catalysts to attenuate peroxynitrite-dependent toxicity (e.g. manganese porphyrins; mitochondrial-targeted antioxidants). In addition, Dr. Radi has shown that peroxynitrite and L-arginine metabolism play central roles during the cellular immune response to pathogens and in particular to the causative agent of Chagas disease, Trypanosoma cruzi. Novel anti-parasitic drug developments from these studies are now in progress. Overall, Dr. Radi´s research activities are directed toward defining the pharmacology and chemical biology of cell and tissue redox reactions and their role in disease states.





Important Publications
Szabó C, H Ischiropoulos and R Radi. Peroxynitrite:  Biochemistry, pathophysiology and development of therapeutics.  Nature Reviews Drug Discovery 6(8):662-680, 2007.
Piacenza  L, G Peluffo and R Radi.  L-arginine-dependent suppression of apoptosis in trypanosoma cruzi:  Contribution of the nitric oxide and the polyamine pathways.  Proc Natl Acad Sci USA 98:7301-7306, 2001.
Radi R, A Denicola, B Alvarez, G Ferrer-Sueta and Rubbo H.  The biological chemistry of peroxynitrite. In: Nitric Oxide, L Ignarro, editor. Academic Press, 57-89, 2000.
Cassina A, R Hodara, J Souza, L Thomson, L Castro, H Ischiropoulos, BA Freeman and R Radi.  Cytochrome c nitration by peroxynitrite. J Biol Chem 275: 21409-21425, 2000.
Radi R, JS Beckman, KM Bush and BA Freeman.  Peroxynitrite oxidation of sulfhydryls: the cytotoxic  potential of superoxide and nitric oxide. J Biol Chem 266:4244-4250, 1991.




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