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INCT 2014: in Stem Cell and Cell Therapy

Grant number: 14/50947-7
Support type:Research Projects - Thematic Grants
Duration: July 01, 2017 - June 30, 2023
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: CNPq - INCTs
Principal Investigator:Dimas Tadeu Covas
Grantee:Dimas Tadeu Covas
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Belinda Pinto Simoes ; Eduardo Antônio Donadi ; Eduardo Magalhães Rego ; Flávio Vieira Meirelles ; Jose Alexandre Marzagão Barbuto ; Klena Sarges Marruaz da Silva ; Lewis Joel Greene ; Lygia da Veiga Pereira ; Marco Antonio Zago ; Roberto Passetto Falcão ; Rodrigo do Tocantins Calado de Saloma Rodrigues ; Valtencir Zucolotto ; Wilson Araújo da Silva Junior
Associated scholarship(s):18/12670-4 - Synthesis of lipid nanocarriers for modulation of tumor and immunocompetent cells, BP.DR
18/13307-0 - Production of lentiviral vectors in scalable conditions for generation of CAR-T cells for cell therapy, BP.MS

Abstract

The present proposal establishes the continuity and expansion of the activities of the National Institute of Science and Technology in Stem Cells and Cell Therapy, one of the National Institutes of Science and Technology created by CNPq/FAPESP in 2008. In that opportunity, we proposed the development of an extensive program of basic and clinical research to understand, isolate, culture and therapeutically use somatic and pluripotent stem cells, both in animal and human models, which also predicted the study on neoplastic stem cells, especially the ones associated with leukemias and Iymphomas. Considering the evolution of scientific knowledge of neoplastic stem cells that culminated in the proposal of a new oncogenesis model where there are multiple subpopulations of Cancer Stem Cells (CSCs) that exhibit higher or lower dominance in tumor mass throughout the evolution of the disease, we decided in this proposal to isolate, culture, characterize single tumor cells (single cell analysis), and study tumor microenvironment with the aim of understanding the intrinsic and extrinsic mechanisrns that lead to cancer genesis. Additionally, we intend to make a great effort to develop innovative therapies against cancer, including immunotherapy and nanomedicine, which might originate pre-clinical and clinical studies in several neoplasias. To carry out this ambitious research plan, we have assembled experts and institutions with acknowledged scientific experience in the areas involved: Cell and Molecular Biology, Genetics, Immunology, Hematology, Oncology, Systems Biology and Bioinformatics, Protein Chemistry, Chemical and Material Engineering, and Veterinary. The participation of principal investigators and collaborators will be fostered in an integrated and complementary way, fruit of the understanding that cancer is a complex issue that could only be effectively approached in a multidisciplinary way. The scientific production of these investigators on the subject? cell therapy?, during the period of development of the project (2009-2014), accounts for more than 470 articles published in refereed journals, representing an increase of more than 50% when compared to the period of five years before INCTC, 7 books and 11 book chapters published and 5 patents deposited. Sixty-six master dissertations, 72 doctorate and 34 post-doctoral theses have been completed. Using the project resources, 28 junior post-doctoral fellowships and 59 Technological and Industrial Development scholarships (DTI), 19 technical support and 20 scientific initiation scholarships have been granted. The scholarships granted throughout the project were essential for the success of the proposal. This proposal gathers 15 Pls from 7 institutions, with expressive academic production, highlighting the publication of 1,358 articles in refereed journals and 14,084 citations and index h equals to 56. 11 has constituted one of the best groups of research on stem cells, therapy and cancer in the country, brought together in an integrated way to address a challenging issue, such as cancer, will enable, great scientific advance which will be able to put the country in a prominent position in the international scene. In general, the set of studies on the area of basic research involves the isolation and characterization of tumor cells and cancer stem cells which will be studied in a detailed level by tools: transcriptome, genomics, epigenomics, cytomics and proteomics that allow the integration of large scale biology and approach to biological systems. The scientific proposal covers three main areas: 1) basic studies for understanding the biology of cancer; 2) development of new therapeutic approaches with emphasis on immunotherapy; and 3) pre-clinical and clinical trials. Educational activities for basic education will be coordinated by the House of Science and will be widely divulged mainly on their educational portal that allows interactive access by teachers, students and post-graduate students involved in the project. Activities will also be conducted at the Museum and Laboratory for Science Teaching, located in the campus of USP-RP. These activities rely on the support of Hemocentro TV, a center for media production, composed of a television studio and an editing suite. The area of education and science dissemination keeps many training and scientific initiation programs designed to teachers and students of elementary and high schools, such as the program “Adopt a Scientist” where postgraduate students are tutors of small groups of students of elementary and high schools with the aim of discussing and studying biology subjects corresponding to the themes of the research carried out by the Institute. Stricto sensu postgraduate education has also been developed as part of the program of knowledge dissemination and specialized professional training. In 2010, two postgraduate courses were organized; they are linked to the Department of Medical Practice, but administered by INCTC investigators. The academic master and doctorate course “Clinical Oncology, Stem Cells and Cell Therapy” and the professional master course “Professional Master in Hemotherapy and Biotechnology” The innovation activities will also be amplified with the support of the USP Innovation Agency and SUPERA - Innovation and Technology Park of Ribeirão Preto. Since 2005, 15 companies have been incubated in the unit Incubator located in the Blood Center. Recently, both units of the SUPERA have been incorporated to the Technological Park that gathers all incubated companies. Additionally, new actions will be developed aiming at the technological development and its transfer to the production sector. Finally, the internationalization activities, jointly with the program of research, science dissemination and diffusion and technology transfer, form the INCTC foundation. This proposal relies on international collaborators, committed to the team. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Patient’s own cells are used in innovative treatment for cancer 

Scientific publications (14)
(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)
SAMPAIO, RAFAEL VILAR; SANGALLI, JULIANO RODRIGUES; CAMARA DE BEM, TIAGO HENRIQUE; AMBRIZI, DEWISON RICARDO; DEL COLLADO, MAITE; BRIDI, ALESSANDRA; CAVALCANTE MENDES DE AVILA, ANA CLARA FAQUINELI; MACABELLI, CAROLINA HABERMANN; OLIVEIRA, LILIAN DE JESUS; DA SILVEIRA, JULIANO COELHO; CHIARATTI, MARCOS ROBERTO; PERECIN, FELIPE; BRESSAN, FABIANA FERNANDES; SMITH, LAWRENCE CHARLES; ROSS, PABLO J.; MEIRELLES, FLAVIO VIEIRA. Catalytic inhibition of H3K9me2 writers disturbs epigenetic marks during bovine nuclear reprogramming. SCIENTIFIC REPORTS, v. 10, n. 1 JUL 13 2020. Web of Science Citations: 0.
SANTOS, FLAVIA L. S.; SLAVOV, SVETOSLAV N.; BEZERRA, RAFAEL S.; SANTOS, ELAINE V.; SILVA-PINTO, ANA C.; MORAIS, ANA L. L.; SA, MARIANA B.; UBIALI, EUGENIA M. A.; DE SANTIS, GIL C.; COVAS, DIMAS T.; KASHIMA, SIMONE. Vaso-occlusive crisis in a sickle cell patient after transfusion-transmitted dengue infection. Transfusion, v. 60, n. 9 JUL 2020. Web of Science Citations: 0.
MACHADO-NETO, JOAO AGOSTINHO; COELHO-SILVA, JUAN LUIZ; DE SOUZA SANTOS, FABIO PIRES; SCHEUCHER, PRISCILA SANTOS; CAMPREGHER, PAULO VIDAL; HAMERSCHLAK, NELSON; REGO, EDUARDO MAGALHAES; TRAINA, FABIOLA. Autophagy inhibition potentiates ruxolitinib-induced apoptosis in JAK2(V617F) cells. INVESTIGATIONAL NEW DRUGS, v. 38, n. 3, p. 733-745, JUN 2020. Web of Science Citations: 0.
CACEMIRO, MAIRA DA COSTA; COMINAL, JUCARA GASTALDI; BERZOTI-COELHO, MARIA GABRIELA; TOGNON, RAQUEL; NUNES, NATALIA DE SOUZA; SIMOES, BELINDA; PEREIRA, ITALO SOUSA; CARLOS, DANIELA; FACCIOLI, LUCIA HELENA; DE FIGUEIREDO-PONTES, LORENA LOBO; FRANTZ, FABIANI GAI; DE CASTRO, FABIOLA ATTIE. Differential cytokine network profile in polycythemia vera and secondary polycythemia. SCIENTIFIC REPORTS, v. 10, n. 1 APR 27 2020. Web of Science Citations: 0.
FENERICH, BRUNA ALVES; FERNANDES, JAQUELINE CRISTINA; RODRIGUES ALVES, ANA PAULA NUNES; COELHO-SILVA, JUAN LUIZ; SCOPIM-RIBEIRO, RENATA; SCHEUCHER, PRISCILA SANTOS; EIDE, CHRISTOPHER A.; TOGNON, CRISTINA E.; DRUKER, BRIAN J.; REGO, EDUARDO MAGALHAES; MACHADO-NETO, JOAO AGOSTINHO; TRAINA, FABIOLA. NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2(V617F)-positive myeloproliferative neoplasm cells. SIGNAL TRANSDUCTION AND TARGETED THERAPY, v. 5, n. 1 JAN 24 2020. Web of Science Citations: 0.
SLAVOV, SVETOSLAV NANEV; GUARAGNA MACHADO, RAFAEL RAHAL; FERREIRA, ALEXANDER RODRIGO; SOARES, CAMILA PEREIRA; ARAUJO, DANIELLE BASTOS; LEAL OLIVEIRA, DANIELLE BRUNA; COVAS, DIMAS TADEU; DURIGON, EDISON LUIZ; KASHIMA, SIMONE. Zika virus seroprevalence in blood donors from the Northeastern region of Sao Paulo State, Brazil, between 2015 and 2017. Journal of Infection, v. 80, n. 1, p. 111-115, JAN 2020. Web of Science Citations: 0.
PICANCO-CASTRO, VIRGINIA; PEREIRA, CRISTIANO GONCALVES; SWIECH, KAMILLA; RIBEIRO MALMEGRIM, KELEN CRISTINA; COVAS, DIMAS TADEU; PORTO, GECIANE SILVEIRA. Emerging CAR T cell therapies: clinical landscape and patent technological routes. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 16, n. 6 DEC 2019. Web of Science Citations: 1.
SLAVOV, S. N.; MARANINCHI SILVEIRA, R.; HESPANHOL, M. R.; SAUVAGE, V.; RODRIGUES, E. S.; FONTANARI KRAUSE, L.; BITTENCOURT, H. T.; CARO, V.; LAPERCHE, S.; COVAS, D. T.; KASHIMA, S. Human pegivirus-1 (HPgV-1) RNA prevalence and genotypes in volunteer blood donors from the Brazilian Amazon. TRANSFUSION CLINIQUE ET BIOLOGIQUE, v. 26, n. 4, p. 234-239, NOV 2019. Web of Science Citations: 0.
SLAVOV, S. N.; CHRISTOVA, I. S.; FERREIRA, A. R.; RODRIGUES, E. S.; BIANQUINI, M. L.; HESPANHOL, M. R.; COVAS, D. T.; KASHIMA, S. Serological evidence of Borrelia circulation among blood donors in the Sao Paulo state, Brazil. Transfusion Medicine, v. 29, n. 5, p. 358-363, OCT 2019. Web of Science Citations: 0.
SLAVOV, SVETOSLAV N.; MACONETTO, JULIANA D. M.; MARTINEZ, EDSON Z.; SILVA-PINTO, ANA CRISTINA; COVAS, DIMAS T.; EIS-HUEBINGER, ANNA MARIA; KASHIMA, SIMONE. Prevalence of hepatitis E virus infection in multiple transfused Brazilian patients with thalassemia and sickle cell disease. Journal of Medical Virology, v. 91, n. 9, p. 1693-1697, SEP 2019. Web of Science Citations: 0.
SLAVOV, SVETOSLAV N.; RODRIGUES, EVANDRA S.; SAUVAGE, VIRGINIE; CARO, VALERIE; DIEFENBACH, CRISTIANE F.; ZIMMERMANN, ANA M.; COVAS, DIMAS T.; LAPERCHE, SYRIA; KASHIMA, SIMONE. Parvovirus B19 seroprevalence, viral load, and genotype characterization in volunteer blood donors from southern Brazil. Journal of Medical Virology, v. 91, n. 7, p. 1224-1231, JUL 2019. Web of Science Citations: 0.
SLAVOV, SVETOSLAV NANEV; SILVEIRA, ROBERTA MARANINCHI; RODRIGUES, EVANDRA STRAZZA; DIEFENBACH, CRISTIANE FRACAO; ZIMMERMANN, ANA MARIA; COVAS, DIMAS TADEU; KASHIMA, SIMONE. Human pegivirus-1 pegivirus-1 (HPgV-1, GBV-C) RNA prevalence and genotype diversity among volunteer blood donors from an intra-hospital hemotherapy service in Southern Brazil. TRANSFUSION AND APHERESIS SCIENCE, v. 58, n. 2, p. 174-178, APR 2019. Web of Science Citations: 2.
COMINAL, JUCARA GASTALDI; CACEMIRO, MAIRA DA COSTA; PINTO-SIMOES, BELINDA; KOLB, HANS-JOCHEM; RIBEIRO MALMEGRIM, KELEN CRISTINA; DE CASTRO, FABIOLA ATTIE. Emerging Role of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Pathogenesis of Haematological Malignancies. STEM CELLS INTERNATIONAL, 2019. Web of Science Citations: 1.
NUNES RODRIGUES ALVES, ANA PAULA; FERNANDES, JAQUELINE CRISTINA; FENERICH, BRUNA ALVES; COELHO-SILVA, JUAN LUIZ; SCHEUCHER, PRISCILA SANTOS; SIMOES, BELINDA PINTO; REGO, EDUARDO MAGALHAES; RIDLEY, ANNE J.; MACHADO-NETO, JOAO AGOSTINHO; TRAINA, FABIOLA. IGF1R/IRS1 targeting has cytotoxic activity and inhibits PI3K/AKT/mTOR and MAPK signaling in acute lymphoblastic leukemia cells. Cancer Letters, v. 456, p. 59-68, 2019. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.