Scholarship 19/00849-2 - Sequenciamento de nova geração, Transformação celular neoplásica - BV FAPESP
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Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS)

Grant number: 19/00849-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date: March 01, 2019
End date: May 31, 2021
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Margaret de Castro
Grantee:Rui Milton Patrício da Silva Junior
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/03989-6 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS), AP.TEM

Abstract

To elucidate the molecular pathogenesis of endocrine tumors, several studies have investigated the role of specific genes regulating the organ development, genes involved in tumorigenesis of other tissues, such as abnormalities in genes that lead to cycle progression and cell division (oncogenes) or genes that block the cell cycle (tumor suppressor genes), miRNAs, and large noncoding (lncRNAs). Significant advances have been observed in the molecular elucidation of various hereditary syndromes that occur with pituitary tumors [(McCune - Albright, Multiple endocrine neoplasia (MEN) type 1 and type 4, Carney's syndrome, and familial isolated pituitary adenoma (FIPA)]; with adrenal tumors (Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex, McCune-Albright, MEN1); and with thyroid tumors (MEN2, Hereditary medullar thyroid carcinoma). All these advances occurred due approaches based on candidate genes and linkage studies, but the molecular pathogenesis of sporadic endocrine tumors has not been completely clarified. The new platforms of next generation sequencing (NGS) present major advantages for the analysis of 1) exoma (Target-seq analysis) 2) epigenomic (either by chromatin immunoprecipitation (ChIP) or promoter DNA methylation analysis), and 3) transcriptome. Therefore, this project aims to use NGS technology to better understand the process of central nervous system (glyomas) and endocrine tumorigenesis. Tumoral tissues will be obtained from patients followed in the Hospital das Clinicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HCFMRP-USP). As controls, normal tissue samples will be obtained at CEMEL (Center of Forensic Medicine) from autopsies of patients with accidental or sudden death from cardiac causes. The NGS certainly will indicate new genes and/or new cell signaling pathways that may be keys of the enlightenment of endocrine tumorigenesis. (AU)

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Scientific publications (11)
(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)
LAZARINI-LOPES, WILLIAN; DO VAL-DA SILVA, RAQUEL A.; DA SILVA-JUNIOR, RUI M. P.; LEITE, JOAO P.; GARCIA-CAIRASCO, NORBERTO. The anticonvulsant effects of cannabidiol in experimental models of epileptic seizures: From behavior and mechanisms to clinical insights. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 111, p. 166-182, . (19/05957-8, 14/50891-1, 19/00849-2)
PORTO DECHANDT, CARLOS ROBERTO; FERRARI, GUSTAVO DUARTE; DOS SANTOS, JONATHAS RODRIGO; CORTES DE OLIVEIRA, JOSE ANTONIO; PATRICIO SILVA-JR, RUI MILTON; SIQUEIRA CUNHA, ALEXANDRA OLIMPIO; GARCIA-CAIRASCO, NORBERTO; ALBERICI, LUCIANE CARLA. Energy Metabolism and Redox State in Brains of Wistar Audiogenic Rats, a Genetic Model of Epilepsy. FRONTIERS IN NEUROLOGY, v. 10, . (14/03989-6, 18/10089-2, 16/23509-4, 15/22327-7, 19/00849-2)
LAZARINI-LOPES, WILLIAN; DO VAL-DA SILVA, RAQUEL A.; DA SILVA-JUNIOR, RUI M. P.; CUNHA, ALEXANDRA O. S.; GARCIA-CAIRASCO, NORBERTO. Cannabinoids in Audiogenic Seizures: From Neuronal Networks to Future Perspectives for Epilepsy Treatment. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 15, . (19/05957-8, 19/00849-2, 14/50891-1)
GOMEZ-NIETO, RICARDO; LOPEZ, DOLORES E.; GARCIA-CAIRASCO, NORBERTO. Editorial: Challenges and Conundrums in Cannabinoid-Based Treatments for Epilepsy Syndromes and Associated Neurobehavioral Comorbidities. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 15, p. 4-pg., . (19/05957-8, 19/16574-2, 14/50891-1, 19/00849-2, 19/02787-4)
SOARES MOTA, JOSE ITALO; PATRICIO SILVA-JUNIOR, RUI MILTON; MARTINS, CLARISSA SILVA; BUENO, ANA CAROLINA; WILDEMBERG, LUIZ EDUARDO; DA SILVA ANTUNES, XIMENE LIMA; OKANOBO OZAKI, JORGE GUILHERME; COELI-LACCHINI, FERNANDA BORCHERS; GARCIA-PERAL, CARLOS; ROCHA OLIVEIRA, ANTONIO EDSON; et al. Telomere length and Wnt/beta-catenin pathway in adamantinomatous craniopharyngiomas. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 187, n. 2, p. 12-pg., . (19/00849-2, 14/03989-6, 19/00860-6)
ALVES, SUELEN SANTOS; PATRICIO DA SILVA-JUNIOR, RUI MILTON; SERVILHA-MENEZES, GABRIEL; HOMOLAK, JAN; SALKOVIC-PETRISIC, MELITA; GARCIA-CAIRASCO, NORBERTO. Insulin Resistance as a Common Link Between Current Alzheimer's Disease Hypotheses. JOURNAL OF ALZHEIMER'S DISEASE, v. 82, n. 1, p. 71-105, . (19/00849-2, 19/05957-8, 14/50891-1, 19/02787-4)
BUENO, ANA CAROLINA; DA SILVA, RUI M. P.; STECCHINI, MONICA F.; MARRERO-GUTIERREZ, JUNIER; DE ALMEIDA E SILVA, DANILLO C.; CARDINALLI, IZILDA; SCRIDELI, CARLOS ALBERTO; JUNQUEIRA, THAIS; MOLINA, CARLOS A. F.; RAMALHO, FERNANDO SILVA; et al. DNA methylation is a comprehensive marker for pediatric adrenocortical tumors. Endocrine-Related Cancer, v. 29, n. 11, p. 15-pg., . (20/03835-0, 19/00860-6, 21/04368-9, 19/00849-2, 14/03989-6)
ALVES, SUELEN SANTOS; PATRICIO DA SILVA JUNIOR, RUI MILTON; DELFINO-PEREIRA, POLIANNA; ALVES GOULART PEREIRA, MARILIA GABRIELLA; VASCONCELOS, ISRAEL; SCHWAEMMLE, HANNA; MAZZEI, RODRIGO FOCOSI; CARLOS, MAIKO LUIZ; ESPREAFICO, ENILZA MARIA; TEDESCO, ANTONIO CLAUDIO; et al. A Genetic Model of Epilepsy with a Partial Alzheimer's Disease-Like Phenotype and Central Insulin Resistance. Molecular Neurobiology, v. 59, n. 6, p. 17-pg., . (19/05957-8, 14/50891-1, 19/16574-2, 19/02787-4, 19/00849-2, 17/21155-3)
LAZARINI-LOPES, WILLIAN; DA SILVA-JUNIOR, RUI M. P.; SERVILHA-MENEZES, GABRIEL; DO VAL-DA SILVA, RAQUEL A.; GARCIA-CAIRASCO, NORBERTO. Cannabinoid Receptor Type 1 (CB1R) Expression in Limbic Brain Structures After Acute and Chronic Seizures in a Genetic Model of Epilepsy. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 14, . (19/00849-2, 19/02787-4, 14/50891-1, 19/05957-8)
ALVES, SUELEN SANTOS; ANTONIO CORTES DE OLIVEIRA, JOSE; LAZARINI-LOPES, WILLIAN; SERVILHA-MENEZES, GABRIEL; GRIGORIO-DE-SANT'ANA, MARIANA; DEL VECCHIO, FLAVIO; FOCOSI MAZZEI, RODRIGO; SOUSA ALMEIDA, SEBASTIAO; MILTON PATRICIO DA SILVA JUNIOR, RUI; GARCIA-CAIRASCO, NORBERTO. Audiogenic Seizures in the Streptozotocin-Induced Rat Alzheimer's Disease Model. JOURNAL OF ALZHEIMER'S DISEASE, v. 94, n. 3, p. 18-pg., . (21/13622-6, 14/50891-1, 17/21155-3, 19/02787-4, 19/00849-2, 19/05957-8)
ALVES, SUELEN SANTOS; SERVILHA-MENEZES, GABRIEL; ROSSI, LETICIA; DA SILVA JUNIOR, RUI MILTON PATRICIO; GARCIA-CAIRASCO, NORBERTO. Evidence of disturbed insulin signaling in animal models of Alzheimer's disease. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 152, p. 23-pg., . (21/14907-4, 14/50891-1, 17/21155-3, 19/02787-4, 19/00849-2, 19/05957-8)