Research
My research interests focus on the intracellular mechanisms involved in platelet signalling and reactive oxygen species (ROS).
Much of my experience to date has being in the role of platelets in sepsis. I have gained significant experience with in vivo (animal models) and isolation and functional analysis of human platelets. As part of my research, I showed that the treatment of rats with lipopolysaccharide (LPS) affects platelet aggregation through intraplatelet ROS generation. The increased intraplatelet ROS production does not contribute to the inhibitory effect of LPS in vivo on platelet aggregation, however, the maintenance of redox balance in LPS-treated rats is fundamental to restore the normal platelet response in these animals. In addition, we showed that the inhibition of rat platelet aggregation by LPS is mediated by cGMP/PKG-dependent mechanisms. PKC and AKT play a role in the inhibitory effects of LPS on platelet aggregation by acting as upstream modulators of the cGMP/ PKG pathway. In my recent work at the University of Reading with Prof Jon Gibbins, we sought to explore the signalling pathways through which LPS in vitro modulates platelets regulation.
My current research is focused on the relationship between zinc ions and platelets with Dr Nicholas Pugh. Zinc ions are also released from platelets and damaged cells and have been shown to act as a platelet agonist. However, the mechanism of zinc-induced platelet activation is not well understood. The group has showed that zinc enters the platelet cytosol and regulates protein phosphorylation-dependent platelet signalling events, leading to granule release and full PKC-mediated aIIbb3-dependent aggregation.
Publications
Synthesis, antiplatelet and antithrombotic activities of resveratrol derivatives with NO-donor properties. Dutra LA, Guanaes JFO, Johmann N, Lopes Pires ME, Chin CM, Marcondes S, Dos Santos JL. Bioorg Med Chem Lett. 2017 Jun 1;27(11):2450-2453. doi: 10.1016/j.bmcl.2017.04.007.
Cross-talking between lymphocytes and platelets and its regulation by nitric oxide and peroxynitrite in physiological condition and endotoxemia. Nádia J. Almeida Cardelli, M. Elisa Lopes-Pires, Pedro H. L. Bonfitto, Heloisa H. Ferreira, Edson Antunes, Sisi Marcondes Life Sci. 2016 Dec 22. pii: S0024-3205(16)30708-1. doi:10.1016/j.lfs.2016.12.013.
PKC and AKT Modulate cGMP/PKG Signaling Pathway on Platelet Aggregation in Experimental Sepsis. Lopes-Pires ME, Naime AC, Almeida Cardelli NJ, Anjos DJ, Antunes E, Marcondes S.PLoS One. 2015 Sep 16;10(9):e0137901. doi: 10.1371/journal.pone.0137901.
Synthesis and Prliminary Evaluation of N-oxide Derivates for tha prevention of Atherothrombotic Events. Rosseto LA, Pires ME, Melchior AC, Bosquesi PL, Pavan AR, Marcondes S, Chung MC7, Santos JL . Molecules. 2015 Oct 7;20(10):18185-200. doi: 10.3390/molecules201018185..
Pharmacological evaluation and preparation of nonsteroidal anti-inflammatory drugs containingna N-acy hydrazone subunit. de Melo TR , Chelucci RC, Pires ME, Dutra LA, Barbieri KP, Bosquesi PL, Trossini GH, Chung MC, dos Santos JL. Int J Mol Sci. 2014 Apr 4;15(4):5821-37. doi:10.3390/ijms15045821.
Antiplatelet and antithrombotic activities of non-steroidal anti-inflammatory drugs containing an N-acyl hydrazone subunit. Chelucci RC, Dutra LA, Lopes-Pires ME, de Melo TR, Bosquesi PL, Chung MC, Dos Santos JL. Molecules. 2014 Feb 17;19(2):2089-99. doi: 10.3390/molecules19022089
Platelet hyperaggregability in high-fat fed rats: a role for intraplatelet reactive-oxygen species production. Monteiro PF, Morganti RP, Delbin MA, Calixto MC, Lopes-Pires ME, Marcondes S, Zanesco A, Antunes E. Cardiovasc Diabetol. 2012 Jan 16;11:5. doi: 10.1186/1475-2840-11-5.
Lipopolysaccharide treatment reduces rat platelet aggregation independent of intracellular reactive-oxygen species generation. Lopes-Pires ME, Casarin AL, Pereira-Cunha FG, Lorand-Metze I, Antunes E, Marcondes S. Platelets. 2012;23(3):195-201. doi: 10.3109/09537104.2011.603065.
