Mapping signaling pathways related to chemoresistance in leukemic cells: a computational approach

• Grant number: 09/18424-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2010
• End date: February 28, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carmen Veríssima Ferreira
• Grantee: Renato Milani
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Chronic myeloid leukemia, characterized by the BCR-ABL fusion gene, still presents deficiencies in patient treatment, as in other kinds of cancer. Chemoresistance is one of the many challenges that need to be addressed in order for a therapy to succeed against this disease. The identification of all molecular mechanisms responsible for promoting and keeping of a multiple drug resistant phenotype is utmostly important for therapeutic protocol evolution. Notwithstanding, little is known about related signaling pathways. Thus, mapping resistant cells signaling events may shed light on chemoresistance mechanisms, as well as pointing to pharmacological intervention targets. Recently, our group defined gene expression, kinome, proteome and phosphoproteome profiles on K562 and Lucena cell lines, besides having developed a computational methodology for large-scale microarray analysis. Proteins involved in several cellular processes are significantly more expressed and/or phosphorylated in Lucena cells (resistant lineage). However, these data are largely volumous and therefore need validation for more specific techniques. In this context, we aim to investigate these networks of proteins through western blotting, RNAi, co-immunoprecipitation etc., in order to determine signaling pathways related to chemoresistance, after a systems biology computational approach to select the most promising targets in silico for validation in vitro. Afterwards, we expect to silence some of the targets to determine their role in the resistance process.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MILANI, Renato. Mapping signaling pathways related to chemoresistance in leukemic cells: a computational approach. 2014. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.