Study of PI3K/AKT signaling pathways in acute myeloid leukemia using selective ion monitoring (SRM).

• Grant number: 13/07675-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2013
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Vitor Marcel Faça
• Grantee: Carolina Hassibe Thomé
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

Acute myeloid leukemia (AML) is a group of diseases with unfavorable prognosis. During leukemogenesis several changes occur in genome, transcriptome, proteome and interactome which allow the development of leukemic cell. The leukemic cell results from deregulation in different signaling pathways, leading cells to increase proliferation, impaired cell differentiation and higher resistance to apoptosis. Among several of these altered signaling pathways, the focus of the current proposal will be the mechanisms related to the PI3K/AKT pathway, which will be studied as a model for early progression, increased proliferation and apoptosis evasion in leukemic cells. Changes described in PI3K/AKT signaling pathway may lead to a constitutive activation of downstream targets, such as AKT kinase. Our research will be based on: the role of the transmembrane adaptor protein LAT2 and the induction of apoptosis or the use of inhibitors, which alter the AKT signaling pathway in hematopoietic cells. To evaluate the regulation of this pathway, we will use targeted proteomics, and develop a panel of proteotypic peptides corresponding to tryptic fragments of relevant proteins related to PI3K/AKT pathway. This panel will be used for large scale monitoring of different samples (treated or not with kinase inhibitors and / or antineoplastic drugs, or even for specific gene knockout) using liquid chromatography coupled to mass spectrometry, referred to as SRM or MRM (selected reaction monitoring, or multiple). With this approach, we intend to obtain important functional, temporal and quantitative information about proteins in PI3K/AKT pathway using AML lineages. The identification of novel protein targets and deeper understanding of cellular signaling pathways are fundamental to the development of new drugs.

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GRASSI, MARIANA LOPES; PALMA, CAMILA DE SOUZA; THOME, CAROLINA HASSIBE; LANFREDI, GUILHERME PAUPERIO; POERSCH, ALINE; FACA, VITOR MARCEL. Proteomic analysis of ovarian cancer cells during epithelial-mesenchymal transition (EMT) induced by epidermal growth factor (EGF) reveals mechanisms of cell cycle control. JOURNAL OF PROTEOMICS, v. 151, n. SI, p. 2-11, JAN 16 2017. (12/09682-4, 13/08755-0, 13/07675-3, 13/08135-2)

THOME, CAROLINA HASSIBE; FERREIRA, GERMANO AGUIAR; PEREIRA-MARTINS, DIEGO ANTONIO; DOS SANTOS, GUILHERME AUGUSTO; ALMEIDA-SILVEIRA, DOUGLAS R.; WEINHAUSER, ISABEL; DE SOUZA, GUSTAVO ANTONIO; HOUTSMA, ROOS; SCHURINGA, JAN JACOB; REGO, EDUARDO M.; et al. The Expression of NTAL and Its Protein Interactors Is Associated With Clinical Outcomes in Acute Myeloid Leukemia. MOLECULAR & CELLULAR PROTEOMICS, v. 20, 2021. (17/23117-1, 13/07675-3, 15/09228-0)

GRASSI, MARIANA LOPES; PALMA, CAMILA DE SOUZA; THOME, CAROLINA HASSIBE; LANFREDI, GUILHERME PAUPERIO; POERSCH, ALINE; FACA, VITOR MARCEL. Proteomic analysis of ovarian cancer cells during epithelial-mesenchymal transition (EMT) induced by epidermal growth factor (EGF) reveals mechanisms of cell cycle control. JOURNAL OF PROTEOMICS, v. 151, p. 10-pg., 2017-01-16. (13/07675-3, 13/08135-2, 12/09682-4, 13/08755-0)

FERREIRA, GERMANO AGUIAR; THOME, CAROLINA HASSIBE; SPER SIMAO, ANA MARIA; SCHEUCHER, PRISCILA SANTOS; ARAUJO SILVA, CLEIDE LUCIA; CHAHUD, FERNANDO; CIANCAGLINI, PIETRO; LEOPOLDINO, ANDREIA MACHADO; REGO, EDUARDO MAGALHAES; FACA, VITOR MARCEL; et al. The lipid raft protein NTAL participates in AKT signaling in mantle cell lymphoma. Leukemia & Lymphoma, v. 60, n. 11, MAY 2019. (13/07675-3)

LANFREDI, GUILHERME P.; THOME, CAROLINA H.; FERREIRA, GERMANO A.; SILVESTRINI, VIRGINIA C.; MASSON, ANA P.; VARGAS, ALESSANDRA P.; GRASSI, MARIANA L.; POERSCH, ALINE; CANDIDO DOS REIS, FRANCISCO J.; FACA, VITOR M.. Analysis of ovarian cancer cell secretome during epithelial to mesenchymal transition reveals a protein signature associated with advanced stages of ovarian tumors. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1869, n. 6, JUN 2021. (13/07675-3, 16/03809-3, 13/08135-2)

THOME, CAROLINA HASSIBE; FERREIRA, GERMANO AGUIAR; PEREIRA-MARTINS, DIEGO ANTONIO; DOS SANTOS, GUILHERME AUGUSTO; ORTIZ, CESAR ALEXANDER; BOTELHO DE SOUZA, LUCAS EDUARDO; SOBRAL, LAYS MARTINS; ARAUJO SILVA, CLEIDE LUCIA; SCHEUCHER, PRISCILA SANTOS; GIL, CRISTIANE DAMAS; et al. NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia. SCIENTIFIC REPORTS, v. 10, n. 1, JUN 25 2020. (13/07675-3, 13/08135-2, 16/03809-3, 17/23117-1)