Our group investigates the mechanisms of the production of oxidants in inflammatory response and how these oxidants affect cell functions.
The production of oxidants by inflammatory cells is an important response to the invasion of microorganisms and cellular damage becouse oxidants act as microbicides and as flags so the cells can contain the damage.
The effects of oxidants on inflammation are controlled by compartmentalization (phagolysosome) and by the fine-tuning between production/removal of them. The change in any of these events will lead to distinct effects. Therefore, our group investigates which oxidants are produced under certain inflammatory conditions and how these oxidants affect the function of proteins and, consequently, the cellular response. By understanding the basic mechanisms involved in these processes, it will be possible to propose more effective therapeutic and diagnostic interventions to control inflammation and infection.
Stimulation of inflammatory cells through the recognition of a pathogen-associated molecular pattern (PAMP) or damage-associated molecular pattern (DAMP) triggers the production of a gamma of oxygen-derived molecules. This process is called inflammatory oxidative burst and releases the anion radical superoxide, hydrogen peroxide, nitric oxide, peroxynitrite and singlet oxygen. Hydrogen peroxide oxidizes chloride to hypochlorous acid in a reaction catalyzed by myeloperoxidase. This enzyme is abundantly expressed in neutrophil granules and is catalytic versatile and so, capable of oxidizing a gamma of substrates besides chloride. Our group demonstrated that uric acid, the end product of purine metabolism in humans, is a physiological substrate for myeloperoxidase. Oxidation of uric acid by the enzyme generates free radical intermediates and the oxidant urate hydroperoxide. This is particularly relevant in atheroma plaque where there is plenty amount of uric acid and inflammatory oxidative burst. Our group has identified the production of urate hydroperoxide by blood neutrophils and correlated the oxidation of uric acid with subclinical atherosclerosis. We also demonstrated that the oxidation o uric acid by myeloperoxidase disturbs the production of hypochlorous acid and the microbicide activity of neutrophils.
We are currently investigating how urate hydroperoxide and other oxidants affect inflammatory and surrounding cells. We have focused on the targeted thiol reactive proteins and the effect of their oxidation in redox signaling.
We also investigate how the production of different oxidants has different effects upon the microbicide activity of inflammatory cells and how bacteria can subvert the cellular immune response.
Currently, our group is composed by three undergraduate students, four PhD students and two post-docs. We have positions open for enthusiastic PhD students and post-docs, all supported by FAPESP.