Researcher, Group Leader, LNBio-CNPEM
Coordinator Mass Spectrometry Facility, LNBio-CNPEM
Phone: +55 19 3512.1267
My research focuses on development of mass spectrometry-based proteomics to discovery oral cancer targets and to understand the regulation of membrane-associated metalloproteinase (ADAM17) through the identification of large-scale complex proteomes, binding partners and post-translational modifications and analysis of cross-linked complexes to map protein-protein interactions.
Mining therapeutic targets in oral cancer
Many advances in research of oral cancer have lead to the gradual molecular understanding of oral cancer. However, the lack of robust biomarkers precludes the early identification of pre-malignant and malignant lesions in order to stratify risk and prognosis. Our strategy is to use complementary models in culture cells, animal and patient tissues to discovery potential candidates to oral cancer targets using mass spectrometry-based proteomics.
Study the regulation of a membrane-associated metalloproteinase, ADAM17
ADAM17, which is also known as TNFα-converting enzyme (TACE), is the major sheddase for the EGF receptor ligands and is considered to be one of the main proteases responsible for the ectodomain shedding of surface proteins. Although this metalloproteinase has an important physiological role, it has been reported to be involved in many diseases, particularly in cancer development. How a membrane-anchored proteinase with an extracellular catalytic domain can be activated by inside-out regulation is not completely understood. Our strategy is to identify new substrates for catalytic domain and partners for non-catalytic domains using mass spectrometry approaches to understand the regulation of this metalloproteinase.
Kawahara R, Lima RN, Domingues RR, Pauletti BA, Meirelles GV, Assis M, Figueira AC, Leme AF. Deciphering the Role of the ADAM17-Dependent Secretome in Cell Signaling. J. Proteome Res. 2014 Mar 13. [Epub ahead of print]
Simabuco FM, Kawahara R, Yokoo S, Granato DC, Miguel L, Agostini M, Aragão AZ, Domingues RR, Flores IL, Macedo CC, Della Coletta R, Graner E, Paes Leme AF. ADAM17 mediates OSCC development in an orthotopic murine model. Mol Cancer. 2014 Feb 5;13:24. doi: 10.1186/1476-4598-13-24.
Winck FV, Belloni M, Pauletti BA, de Lima Zanella J, Domingues RR, Sherman NE, Paes Leme AF. Phosphoproteome analysis reveals differences in phosphosite profiles between tumorigenic and non-tumorigenic epithelial cells. J Proteomics. 2013 Nov 7. doi:pii: S1874-3919(13)00554-X. 10.1016/j.jprot.2013.10.039
Aragão AZ, Nogueira ML, Granato DC, Simabuco FM, Honorato RV, Hoffman Z, Yokoo S, Laurindo FR, Squina FM, Zeri AC, Oliveira PS, Sherman NE, Paes Leme AF. Identification of Novel Interaction between ADAM17 (a Disintegrin and Metalloprotease 17) and Thioredoxin-1. J Biol Chem. 2012 Dec 14;287(51):43071-82.
Novel processed form of syndecan-1 shed from SCC-9 cells plays a role in cell migration. Aragão AZ, Belloni M, Simabuco FM, Zanetti MR, Yokoo S, Domingues RR, Kawahara R, Pauletti BA, Gonçalves A, Agostini M, Graner E, Coletta RD, Fox JW, Leme AF. PLoS One. 2012;7(8):e43521. doi: 10.1371/journal.pone.0043521.
Paes Leme AF, Sherman NE, Smalley DM, Sizukusa LO, Oliveira AK, Menezes MC, Fox JW, Serrano SM. Hemorrhagic Activity of HF3, a Snake Venom Metalloproteinase: Insights from the Proteomic Analysis of Mouse Skin and Blood Plasma. J Proteome Res, 2012, 11(1):279-291.
Paes Leme AF, Escalente T, Pereira JGC, Oliveira AK, Sanchez EF, Gutiérrez JM, Serrano SMT, Fox JW. High resolution analysis of snake venom metalloproteinase (SVMP) peptide bond cleavage specificity using proteome based peptide libraries and mass spectrometry. J Proteomics, 1;74(4):401-10, 2011.
02/1996 – 12/1999 “Effect of fluoridated dentifrice and acidulated phosphate fluoride application on early artificial carious lesions”, School of Dentistry of Piracicaba (FOP), UNICAMP, tutor: Prof. Dr. Jaime A. Cury, Dep. Physiological Sciences, UNICAMP, Brazil.
01/2000 – 02/2002 Master in Science: “In situ effect of frequent sucrose exposure on enamel demineralization and on plaque composition after APF application and F dentifrice use”, tutor: Prof. Dr. Jaime A. Cury, Dep. Physiological Sciences, FOP, UNICAMP, Brazil.
03/2002 – 09/2005 PhD thesis: “Effects of sucrose on the extracellular matrix of plaque-like biofilm formed in vivo, studied by proteomic analysis”, tutor: Prof. Dr. Jaime A. Cury, Dep. Physiological Sciences, FOP, UNICAMP, Brazil.
02/2006 – 04/2007 Post-doc I: “The effect of PIII snake venom metalloproteinase on cell and plasma targets”, supervisor: Prof. Dr. Solange Serrano, Dep. Biochemistry, Butantan Institute, São Paulo, Brazil.
05/2007- 08/2007 Post-doc II: “Analysis of the subproteomes of proteinases and target substrates of a PIII snake venom metalloproteinase” supervisors: Drs. Jay W. Fox and Nicholas E. Sherman, University of Virginia, Charlottesville, USA.
09/2007 – 02/2009 Post-doc III: “Hemorrhagic effects of HF3, a snake venom metalloproteinase: insights from the proteomic/peptidomic analysis of mouse skin and blood plasma”, supervisor: Prof. Dr. Solange Serrano, Dep. Biochemistry, Butantan Institute, São Paulo, Brazil.
03/2009 – 05/2009 Post-doc IV: “High resolution analysis of snake venom metalloproteinase (SVMP) peptide bond cleavage specificity using proteome based peptide libraries and mass spectrometry”, supervisor: Drs. Jay W. Fox, Nicholas E. Sherman, University of Virginia, Charlottesville, USA.