Identification of alternative membrane protein isoforms as potential biomarkers for tumors with poor prognosis and scarce therapeutic options

• Grant number: 20/14158-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2021
• End date: May 23, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Pedro Alexandre Favoretto Galante
• Grantee: Filipe Ferreira dos Santos
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
• Associated scholarship(s): 23/07144-0 - Comprehensive landscape of the human cellular membrane proteins' transcriptome over neurodevelopmental stages of brain organoid models, BE.EP.DR

Abstract

Splicing is an essential step of gene expression in eukaryotes. Many loci of the human genome, after being transcribed, are processed in an alternative way (alternative splicing), generating different isoforms of mRNAs for the same gene (locus). It is known that changes in the splicing pattern are related to the development of approximately 15% of genetic diseases and, of course, to several types of malignant tumors in humans. Cancer cells, in general, have a high rate of alternative splicing, including tumor-specific isoforms. In this project, we will seek for alternative splicing events in genes encoding cell membrane proteins that occur specifically or preferentially in tumor samples. To do so, we will use gene expression data from a set of ~11,000 samples of 33 Cancer types and a wide repertoire of computational tools (bioinformatics) to process, integrate and analyze this data. As we will select only isoforms that are either specific or preferentially found in tumors from events in genes encoding cell membrane proteins, we expect, at the end of this project, to have a promising set of biomarkers for the deliberate development of new targeted therapies for tumor treatment. In our analyses, we will pay special attention to Cancer types whose treatment options remain scarce, such as Diffuse Intrinsic Pontine Glioma, Glioblastoma, and Pancreatic Adenocarcinoma, for which we already have promising preliminary results. All results generated here will be organized in a database with free access and disseminated to the scientific community. In conclusion, we hope that our findings will help in the development of new targeted therapies for Cancer, especially for those tumors with a high mortality rate and that do not yet have good target drugs or highly effective treatments. (AU)

Scientific publications

(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)

DE SOUZA, ANACLETO SILVA; AMORIM, VITOR MARTINS DE FREITAS; GUARDIA, GABRIELA D. A.; DOS SANTOS, FELIPE R. C.; DOS SANTOS, FILIPE F.; DE SOUZA, ROBSON FRANCISCO; JUVENAL, GUILHERME DE ARAUJO; HUANG, YIHUA; GE, PINGJU; JIANG, YINAN; et al. Molecular Dynamics Analysis of Fast-Spreading Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Their Effects on the Interaction with Human Angiotensin-Converting Enzyme 2. ACS OMEGA, v. 7, n. 35, p. 10-pg., 2022-08-24. (20/06091-1, 17/18246-7, 17/19541-2, 20/04680-0, 19/00195-2, 16/09047-8, 18/15579-8, 18/07366-4, 20/14158-9)

DE SOUZA, ANACLETO SILVA; DE FREITAS AMORIM, VITOR MARTINS; GUARDIA, GABRIELA D. A.; DOS SANTOS, FILIPE F.; ULRICH, HENNING; GALANTE, PEDRO A. F.; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern: A Perspective for Emerging More Transmissible and Vaccine-Resistant Strains. Viruses-Basel, v. 14, n. 4, p. 21-pg., 2022-04-01. (18/07366-4, 20/06091-1, 19/00195-2, 16/09047-8, 20/14158-9, 20/04680-0, 17/18246-7, 17/19541-2, 18/15579-8)