Education & Training
- B.S., Biological Sciences, Biology, University of Buenos Aires, Argentina-1998
- Ph.D., Biochemistry, University of Buenos Aires, Argentina- 2001
- Post-doctoral fellow, Biochemistry, University of Alabama at Birmingham- 2006
- Masters-Business Administration, University of Pittsburgh, 2011
Research Interest Summary
Research Categories
Research Interests
Nitrated fatty acids: My group demonstrated the beneficial effects of NO2-OA in a wide variety of preclinical animal models (e.g. heart and kidney ischemia-reperfusion, dermal immune responses, restenosis after endoluminal injury, lung injury, atherosclerosis development, diabetes, metabolic syndrome and endotoxemia), motivating its development as a drug and the ongoing clinical trials. Due to structural and mechanistic homology, endogenous nitro-conjugated linoleic acid exerts many of the same physiological responses as exogenously administered NO2-OA. Our current effort in this area is to bridge the pharmacological aspects of NO2-OA with dietary approaches for future clinical trials using dietary conjugated linoleic acid and nitrite.
Furan Fatty acids: Our recent discovery of high levels of furan fatty acids (up to 1 %) upon treatment of human healthy volunteers with an FDA approved omega-3 ethyl ester drug (Lovaza, GlaxoSmithKline) led us to evaluate their metabolic effects as well as test its levels in fish oil and pharmaceutical preparations. Furan fatty acid metabolic responses in mice evoke human fish oil and omega-3 fatty acid pharmacology, underscoring their role as important lipid signaling mediators. Current work includes engineered furan fatty acids for click chemistry and photoreactivity investigations in biological systems. Our long-term goal is to design new pharmacological approaches to treat dyslipidemias based on modified FuFA.
Oxidative stress and thiol chemistry: the main signaling target for dietary electrophilic compounds is activation of Nrf2 signaling. The interplay between electrophiles, Nrf2, thiol homeostasis and their physiological consequences are at the center of our research and guide many of our pharmacological developments. On the biochemistry side, we are currently investigating a non-canonical pathway of GSH/GSSG regulation by electrophiles that involves direct an indirect modulation of glutathione reductase activity. On the physiological end, we are investigating the unexpected role Nrf2 exerts on vascular and renal homeostasis.
Representative Publications
Hicks, K. G., Cluntun, A. A., Schubert, H. L., Hackett, S. R., Berg, J. A., Leonard, P. G., Ajalla Aleixo, M. A., Zhou, Y., Bott, A. J., Salvatore, S. R., Chang, F., Blevins, A., Barta, P., Tilley, S., Leifer, A., Guzman, A., Arok, A., Fogarty, S., Winter, J. M., Ahn, H. C., Allen, K. N., Block, S., Cardoso, I. A., Ding, J., Dreveny, I., Gasper, W. C., Ho, Q., Matsuura, A., Palladino, M. J., Prajapati, S., Sun, P., Tittmann, K., Tolan, D. R., Unterlass, J., VanDemark, A. P., Vander Heiden, M. G., Webb, B. A., Yun, C. H., Zhao, P., Wang, B., Schopfer, F. J., Hill, C. P., Nonato, M. C., Muller, F. L., Cox, J. E., and Rutter, J. (2023) Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase. Science 379, 996-1003
Bago, A., Cayuela, M. L., Gil, A., Calvo, E., Vazquez, J., Queiro, A., Schopfer, F. J., Radi, R., Serrador, J. M., and Iniguez, M. A. (2023) Nitro-oleic acid regulates T cell activation through post-translational modification of calcineurin. Proc Natl Acad Sci U S A 120, e2208924120
Carreno, M., Pires, M. F., Woodcock, S. R., Brzoska, T., Ghosh, S., Salvatore, S. R., Chang, F., Khoo, N. K. H., Dunn, M., Connors, N., Yuan, S., Straub, A. C., Wendell, S. G., Kato, G. J., Freeman, B. A., Ofori-Acquah, S. F., Sundd, P., Schopfer, F. J., and Vitturi, D. A. (2022) Immunomodulatory actions of a kynurenine-derived endogenous electrophile. Sci Adv 8, eabm9138
Fazzari, M., Woodcock, S. R., Rowart, P., Ricart, K., Lancaster, J. R., Jr., Patel, R., Vitturi, D. A., Freeman, B. A., and Schopfer, F. J. (2021) Endogenous generation of nitro-fatty acid hybrids having dual nitrate ester (RONO2) and nitroalkene (RNO2) substituents. Redox Biol 41, 101913
Jobbagy, S., Vitturi, D. A., Salvatore, S. R., Pires, M. F., Rowart, P., Emlet, D. R., Ross, M., Hahn, S., St Croix, C., Wendell, S. G., Subramanya, A. R., Straub, A. C., Tan, R. J., and Schopfer, F. J. (2020) Nrf2 activation protects against lithium-induced nephrogenic diabetes insipidus. JCI Insight 5
Jobbagy, S., Vitturi, D. A., Salvatore, S. R., Turell, L., Pires, M. F., Kansanen, E., Batthyany, C., Lancaster, J. R., Jr., Freeman, B. A., and Schopfer, F. J. (2019) Electrophiles modulate glutathione reductase activity via alkylation and upregulation of glutathione biosynthesis. Redox Biol 21, 101050
Prentice, K. J., Wendell, S. G., Liu, Y., Eversley, J. A., Salvatore, S. R., Mohan, H., Brandt, S. L., Adams, A. C., Serena Wang, X., Wei, D., FitzGerald, G. A., Durham, T. B., Hammond, C. D., Sloop, K. W., Skarke, C., Schopfer, F. J., and Wheeler, M. B. (2018) CMPF, a Metabolite Formed Upon Prescription Omega-3-Acid Ethyl Ester Supplementation, Prevents and Reverses Steatosis. EBioMedicine 27, 200-213
Hansen, A. L., Buchan, G. J., Ruhl, M., Mukai, K., Salvatore, S. R., Ogawa, E., Andersen, S. D., Iversen, M. B., Thielke, A. L., Gunderstofte, C., Motwani, M., Moller, C. T., Jakobsen, A. S., Fitzgerald, K. A., Roos, J., Lin, R., Maier, T. J., Goldbach-Mansky, R., Miner, C. A., Qian, W., Miner, J. J., Rigby, R. E., Rehwinkel, J., Jakobsen, M. R., Arai, H., Taguchi, T., Schopfer, F. J., Olagnier, D., and Holm, C. K. (2018) Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling. Proc Natl Acad Sci U S A 115, E7768-e7775