INSTITUTO DE CIÊNCIAS BIOMÉDICAS

|

Excelência em Ensino e Pesquisa

Profa.Dra. Edna Teruko Kimura

Profa.Dra. Edna Teruko Kimura

Posição atual: Professor Titular

Doutorado: 1994

Orientador: Mestrado e Doutorado

Visite nosso laboratório

Currículo Lattes

DESCRIÇÃO DA LINHA DE PESQUISA

  • Oncogênese das neoplasias da célula folicular tiroidiana
  • Detecção e análise funcional de microRNAs
  • Fatores de crescimento e tiróide: função de TGF-b e sua sinalização
  • Fatores de crescimento e Iodo na proliferação celular
  • Genoma Humano do Câncer relacionado ao Câncer de Tiróide

SUMÁRIO DOS PROJETOS DE PESQUISA EM ANDAMENTO

O câncer de tiroide é a neoplasia mais frequente do sistema endócrino. Nosso laboratório investiga os eventos moleculares que regulam o processo neoplásico da célula folicular tiroidiana, do bócio ao câncer, e suas implicações para o diagnóstico e tratamento do câncer de tiroide. Dentre os eventos moleculares estudados em nosso laboratório estão rearranjos cromossômicos do tipo RET/PTC e mutações nos genes BRAF e RAS, genes-chave que regulam vias de sinalização importantes no controle da proliferação e morte celular, além de alterações na expressão de pequenos RNAs não codificantes, os microRNAs (miRNA). Atualmente o Laboratório integra e coordena o NapmiR (Núcleo de Pesquisa em microRNA) http://www.napmirusp.com.br/.

Utilizamos em nossa pesquisa modelos in vitro de células tumorais, e in vivo de camundongos transgênicos, além de amostras teciduais obtidas de pacientes com câncer de tiroide. Nossa rotina laboratorial inclui modernas técnicas de biologia celular e molecular como Real Time-PCR, Imuno-histoquímica, expressão condicional de oncogenes, interferência de RNA, PCR Arrays Serial Analysis of Gene Expression (SAGE) e Sequenciamento em Larga Escala “Deep Sequencing” para elucidar:

  • A influência do microRNA na oncogênese e progressão do câncer de tiroide
  • A função da mutação de BRAF no câncer de tiroide e os efeitos da expressão condicional e inibição de oncogenes na proliferação e apoptose das células foliculares tiroidianas
  • A contribuição da família de TGF-b (TGF-beta e Activina) e seu sistema de sinalização para a patogênese do bócio e do câncer de tiroide
  • A função de galectina-3 na progressão tumoral da tiroide
  • O papel de IGF e IGFBP em modelo experimental de tiroide
  • Influência de altas doses de iodo na biologia da célula folicular tiroidiana in vitro e in vivo
  • Os efeitos da inibição farmacológica da função tiroidiana in vivo;

Alunos de pós-graduação:

Aline Nogueira Olivé
Cesar Seigi Fuziwara
Murilo Vieira Geraldo
Julio Cézar Marques Ricarte-Filho

Alunos de Iniciação científica:

Felipe Martins Elias
Luana da Silva Rodrigues

 PUBLICAÇÕES RELEVANTES

Fuziwara CS, Kimura ET  High iodine blocks a Notch/miR-19 loop activated by the BRAFV600E oncoprotein and restores the response to TGFbeta in thyroid follicular cells. Thyroid. 2014 Mar; 24 (3):453-462.

Fuziwara CS, Kimura ET  Modulation of Deregulated MicroRNAs for Target Therapy in Thyroid Cancer. 2014. In: Sarkar FH, editor. MicroRNA Targeted Cancer Therapy. 1 ed. Cham: Springer International Publishing. pp. 219-237.

Geraldo MV, Fuziwara CS, Friguglieti CU, Costa RB, Kulcsar MA, Yamashita AS, Kimura ET. MicroRNAs miR-146-5p and let-7f as prognostic tools for aggressive papillary thyroid carcinoma: a case report.Arq Bras Endocrinol Metabol. 2012 Nov;56(8):552-7.

Yamashita AS, Geraldo MV, Fuziwara CS, Kulcsar MA, Friguglietti CU, Costa RB, Baia GS, Kimura ET. Notch pathway is activated by MAPK signaling and influences papillary thyroid cancer proliferation. Transl Oncol. 2013 Apr; 6(2):197-205.

Fuziwara CS, Geraldo MV, Kimura ET. Let-7 and Cancer. In: Dahiya N, editor. MicroRNA Let-7: role in human diseases and drug discovery. 2012, New York: Nova Science Publishers. pp. 109-124.

Leoni SG, Kimura ET, Santisteban P, De la Vieja A.Regulation of thyroid oxidative state by thioredoxin reductase has a crucial role in thyroid responses to iodide excess. Mol Endocrinol. 2011 Nov;25(11):1924-35. doi: 10.1210/me.2011-0038. Epub 2011 Sep 8.

Geraldo MV, Yamashita AS, Kimura ETMicroRNA miR-146b-5p regulates signal transduction of TGF-β by repressing SMAD4 in thyroid cancer. Oncogene. 2011 Aug 29. doi: 10.1038/onc.2011.381.

Matsuo SE, Fiore AP, Siguematu SM, Ebina KN, Friguglietti CU, Ferro MC, Kulcsar MA, Kimura ETExpression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues. Arq Bras Endocrinol Metabol. 2010 Jun;54(4):406-12.

Ricarte-Filho JC, Fuziwara CS, Yamashita AS, Rezende E, da-Silva MJ, Kimura ETEffects of let-7 microRNA on Cell Growth and Differentiation of Papillary Thyroid Cancer. Transl Oncol. 2009 Dec;2(4):236-41.

Fiore AP, Fuziwara CS, Kimura ETHigh iodine concentration attenuates RET/PTC3 oncogene activation in thyroid follicular cells. Thyroid. 2009 Nov;19(11):1249-56.

Chen X, Mitsutake N, LaPerle K, Akeno N, Zanzonico P, Longo VA, Mitsutake S, Kimura ET, Geiger H, Santos E, Wendel HG, Franco A, Knauf JA, Fagin JA. Endogenous expression of Hras(G12V) induces developmental defects and neoplasms with copy number imbalances of the oncogene. Proc Natl Acad Sci U S A. 2009 May 12;106(19):7979-84. Epub 2009 Apr 29.

Baia GS, Stifani S, Kimura ET, McDermott MW, Pieper RO, Lal A. Notch activation is associated with tetraploidy and enhanced chromosomal instability in meningiomas. Neoplasia. 2008 Jun;10(6):604-12.

Leoni SG, Galante PA, Ricarte-Filho JC, Kimura ET.Differential gene expression analysis of iodide-treated rat thyroid follicular cell line PCCl3. Genomics. 2008 Apr;91(4):356-66. Epub 2008 Feb 12.

Baia GS, Dinca EB, Ozawa T, Kimura ET, McDermott MW, James CD, VandenBerg SR, Lal A. An orthotopic skull base model of malignant meningioma. Brain Pathol. 2008 Apr;18(2):172-9. Epub 2007 Dec 17.

Kimura ET, Matsuo SE, Ricarte-Filho JC. [TGFbeta, activin and SMAD signalling in thyroid cancer]. Arq Bras Endocrinol Metabol. 2007 Jul;51(5):683-9. Review

Fagin JA, Ward LS, Kimura ET[Thyroid cancer: past, present and future]. Arq Bras Endocrinol Metabol. 2007 Jul;51(5):641-2.

Golbert L, Kolling JH, Leitão AH, Martins L, Kimura ET, Maia AL. H-RAS gene expression in human multinodular goiter. Histol Histopathol. 2007 Apr;22(4):409-16.

Ricarte Filho JC, Kimura ET[MicroRNAs: novel class of gene regulators involved in endocrine function and cancer]. Arq Bras Endocrinol Metabol. 2006 Dec;50(6):1102-7.

Matsuo SE, Leoni SG, Colquhoun A, Kimura ETTransforming growth factor-beta1 and activin A generate antiproliferative signaling in thyroid cancer cells. J Endocrinol. 2006 Jul;190(1):141-50.

Maciel, RM; Kimura, ET;Cerutti, JM. Pathogenesis of differentiated thyroid cancer (papillary and follicular).  Arq Bras Endocrinol Metabol. v. 49, p. 691-700, 2005. (in process).

Oler, G; Ebina, KN; Michaluart Jr, P, Kimura, ET; Cerutti, J. Investigation of BRAF mutation in a series of papillary thyroid carcinoma and matched-lymph node metastasis reveals a new mutation in metastasis. Clin Endocrinol., v. 62, p. 509-11, 2005.

Maciel, RM; Seelaender, MC; Kimura, ET; Cerutti, JM. Pathogenesis of differentiated thyroid cancer (papillary and follicular)]Arq Bras Endocrinol Metabol. 2005 Oct;49(5):691-700. Epub 2006 Jan 23. Portuguese. In: Clin Endocrinol (Oxf). Apr;62(4):509-11. 2005. 

Kimura, ET; Vanvooren, V; Van Sande, J; Nikiforov, YE; Fagin, JA. Autonomously functioning thyroid nodules are not associated with BRAF mutations.Clin Endocrinol (Oxf) 60:394-6, 2004.

Matsuo, SE; Martins, L; Leoni, SG; Hajjar, D; Ricarte-Filho, JCM; Ebina, KN; Kimura, ET. Marcadores Biológicos de tumores tiroidianos. Arq Bras Endocrinol Metab 48: 114-125, 2004.

Nikiforova, MN; Kimura, ET; Gandhi, M; Knauf, JA; Basolo, F; Zhu, Z; Giannini, R; Salvatore, G; Fusco, A; Santoro, M; Fagin, JA; Nikiforov, YE. Braf mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 88:5399-404, 2003.

Knauf, JA; Ouyang, B; Croyle, M; Kimura, ET; Fagin, JA. Acute expression of RET/PTC induces isozyme-specific activation and subsequent downregulation of PKCepsilon in PCCL3 thyroid cells. Oncogene 2003 22:6830-8, 2003.

Cerutti, JM; Ebina, KN; Martins, L; Maciel, RMB; Kimura, ETExpression of smad4 and smad7 in human thyroid follicular carcinoma cell lines. J Endocrinol Invest 26, 516-21, 2003.

Kimura, ET; Nikiforova, MN; Zhu, Z; Knauf, JA; Nikiforov, YE; Fagin, JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RASBRAF signalling pathway in papillary thyroid carcinoma. Cancer Res  63:1454-57, 2003. 

Matsuo, SE; Ebina, KN; Friguglietti, C; Kulcsar, MA; Kimura, ETActivin bB expression in rat experimental goiter and human thyroid tumors. Thyroid13:239-47, 2003.

Martins, L; Matsuo, SE; Ebina, KN;Kulcsar, MAV; Friguglietti, CUM; Kimura, ETGalectin-3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors. J Clin Endocrinol Metab, 87:4806-4810, 2002.

PUBLICAÇÕES GENOMA

Mondego JM, Vidal RO, Carazzolle MF, Tokuda EK, Parizzi LP, Costa GG, Pereira LF, Andrade AC, Colombo CA, Vieira LG, Pereira GA; Brazilian Coffee Genome Project Consortium. An EST-based analysis identifies new genes and reveals distinctive gene expression features of Coffea arabica and Coffea canephora. BMC Plant Biol. 2011 Feb 8;11:30.

Reis EM, Ojopi EP, Alberto FL, Rahal P, Tsukumo F, Mancini UM, Guimaraes GS, Thompson GM, Camacho C, Miracca E, Carvalho AL, Machado AA, Paquola AC, Cerutti JM, da Silva AM, Pereira GG, Valentini SR, Nagai MA, Kowalski LP, Verjovski-Almeida S, Tajara EH, Dias-Neto E; Head and Neck Annotation Consortium (Leoni SG, Matsuo SE, Kimura, ET). Large-scale Transcriptome Analyses Reveal New Genetic Marker Candidates of Head, Neck, and Thyroid cancer. Cancer Res  65:1693-99, 2005.

Monteiro-Vitorello CB, Camargo LEA, Van Sluys MA, Kitajima JP, Truffi D, do Amaral AM, Harakava R, de Oliveira JCF, Wood D, de Oliveira MC, Miyaki C, Takita MA, da Silva ACR, Furlan LR,  Carraro DM, Camarotte G, Almeida Jr. NF, Carrer H, Coutinho LL, El-Dorry HA, Ferro MIT, Gagliardi PR,  Giglioti E, Goldman MHS, Goldman GH, Kimura, ET; Ferro ES, Kuramae EE, Lemos EGM, Lemos MVF, Mauro SMZ, Machado MA, Marino CL,  Menck CF, Nunes LR, Oliveira RC, Pereira GG, Siqueira W,  de Souza AA, Tsai SM, Zanca AS, Simpson AJG, Brumbley SM, Setúbal JC. The Genome Sequence of the Gram-Positive Sugarcane Pathogen Leifsonia xyli subsp. xyli Mol Plant Microbe Interact 17: 827-836, 2004.

The Ludwig-FAPESP Transcript Finishing Initiative. Sogayar MC, Camargo AA, Bettoni F, Carraro DM, Pires LC, Parmigiani RB, Ferreira EN, de Sa Moreira E, do Rosario D de O Latorre M, Simpson AJ, Cruz LO, Degaki TL, Festa F, Massirer KB, Sogayar MC, Filho FC, Camargo LP, Cunha MA, De Souza SJ, Faria M Jr, Giuliatti S, Kopp L, de Oliveira PS, Paiva PB, Pereira AA, Pinheiro DG, Puga RD, S de Souza JE, Albuquerque DM, Andrade LE, Baia GS, Briones MR, Cavaleiro-Luna AM, Cerutti JM, Costa FF, Costanzi-Strauss E, Espreafico EM, Ferrasi AC, Ferro ES, Fortes MA, Furchi JR, Giannella-Neto D, Goldman GH, Goldman MH, Gruber A, Guimaraes GS, Hackel C, Henrique-Silva F; Kimura, ET; Leoni SG, Macedo C, Malnic B, Manzini B CV, Marie SK, Martinez-Rossi NM, Menossi M, Miracca EC, Nagai MA, Nobrega FG, Nobrega MP, Oba-Shinjo SM, Oliveira MK, Orabona GM, Otsuka AY, Paco-Larson ML, Paixao BM, Pandolfi JR, Pardini MI, Passos Bueno MR, Passos GA, Pesquero JB, Pessoa JG, Rahal P, Rainho CA, Reis CP, Ricca TI, Rodrigues V, Rogatto SR, Romano CM, Romeiro JG, Rossi A, Sa RG, Sales MM, Sant’Anna SC, Santarosa PL, Segato F, Silva WA Jr, Silva ID, Silva NP, Soares-Costa A, Sonati MF, Strauss BE, Tajara EH, Valentini SR, Villanova FE, Ward LS, Zanette DL; Ludwig-FAPESP Transcript Finishing Initiative. A transcript finishing initiative for closing gaps in the human transcriptome Genome Res 14:1413-23, 2004.

Nascimento AL, Ko AI, Martins EA, Monteiro-Vitorello CB, Ho PL, Haake DA, Verjovski-Almeida S, Hartskeerl RA, Marques MV, Oliveira MC, Menck CF, Leite LC, Carrer H, Coutinho LL, Degrave WM, Dellagostin OA, El-Dorry H, Ferro ES, Ferro MI, Furlan LR, Gamberini M, Giglioti EA, Goes-Neto A, Goldman GH, Goldman MH, Harakava R, Jeronimo SM, Junqueira-de-Azevedo IL; Kimura, ET; Kuramae EE, Lemos EG, Lemos MV, Marino CL, Nunes LR, de Oliveira RC, Pereira GG, Reis MS, Schriefer A, Siqueira WJ, Sommer P, Tsai SM, Simpson AJ, Ferro JA, Camargo LE, Kitajima JP, Setubal JC, Van Sluys MA Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis J Bacteriol 186:2164-72, 2004.

Brentani H, Caballero OL, Camargo AA, Da Silva AM, Da Silva WA Jr, Neto ED, Grivet M, Gruber A, Guimaraes PE, Hide W, Iseli C, Jongeneel CV, Kelso J, Nagai MA, Ojopi EP, Osorio EC, Reis EM, Riggins GJ, Simpson AJ, De Souza S, Stevenson BJ, Strausberg RL, Tajara EH, Verjovski-Almeida S, The Human Cancer Genome Project/Cancer Genome Anatomy Project Annotation Consortium, Acencio ML, Bengtson MH, Bettoni F, Bodmer WF, Briones MR, Camargo LP, Cavenee W, Cerutti JM, Andrade LE, Dos Santos PC, Costa MC, Da Silva IT, Estecio MR, Sa Ferreira K, Furnari FB, Faria M Jr, Galante PA, Guimaraes GS, Holanda AJ; Kimura, ET et al. The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags. Proc Natl Acad Sci U S A.100:13418-13423, 2003.

Van Sluys MA, Oliveira MC, Monteiro-Vitorello, Furlan LR, Camargo LEA, Silva ACR, Moon DH, Takita MA, Lemos EGM, Machado MA, Ferro MIT, Goldman MHS, da Silva FR, Goldman GH, Lemos MVF, El-Dorry H, Tsai SM, Carrer H, Carraro DM, Oliveira RC,  Nunes LR, Siqueira WJ, Coutinho Ll; Kimura, ET et al. Comparative analyses of the complete genome sequences of Pierce’s Disease and Citrus Variagated Chlorosis strains of Xylella fastidiosa. J Bacteriol, 185:1018-26, 2003.

Camargo AA, Samaia HPB, Dias-Neto E, Simão DF,  Migotto IA, Briones MRS, Costa FF, Nagai MA, Verjovski-Almeida S, Zago MA, Andrade LEC, Carrer H, El-Dorry HFA, Enilza M.Espreafico EM, Gama AH, Giannella-Neto D, Goldman GH, Gruber A, Christine Hackel C; Kimura, ET et al. The contribution of 700,000 open reading frames expressed sequence tags to the definition of the human transcriptome. Proc Natl Acad Sci USA, 98: 12103-12108, 2001.

de Souza SJ, Camargo AA, Briones MRS, Costa FF, Nagai MA, Verjovsk-Almeida S, Zargo MA, Andrade LEC, Carrer H, El-Dorry HFA, Espreafico EM, Habr-Gama A, Giannela-Neto D, Goldman GH, Gruber A, Hackel C; Kimura, ET; Maciel RMB, Marie SKN, Martins EAL, Nóbrega MP, Pacó-Larson ML, Pardini MIMC, Pereira GG, Pesquero JB, Rodrigues V, Rogatto SR, Silva IDCG, Sogavar MC, Sonati MF, Tajara MH, Valentini SR, Acencio M, Alberto FL, Amaral MEJ, Aneas I, Bengstson MH, Carraro DM, Carvalho AF, Carvalho LH, Cerutti, JM, Corrêa MLC, Costa MCR, Costa-Neto CM, Curcio C, Gushiken T, Ho PL, Kimura E, Leite LCC, Maia G, Majumder P, Martins M, Matsukuma A, Melo ASA, Mestriner CA, Miracca EC Miranda DC, Nascimento ALTO, Nóbrega FG, Ojopi EPB, Pandolfi JRC, Pessoa LG, Rahal P, Rainho CA, Ro’s N, As RG, Sales MS, Silva NP, Silva-Jr WD, Simão DF, Sousa JF, Stecconi RR, Tsukumo F, Valente V, Zalcberg H, Bretani RR, Reis LFL, Dias-Neto E, Simpson AJG. Identification of human chromosome 22 transcribed sequences with Open Reading Frames ESTs. Proc Natl Acad Sci USA, 97:12690 -12693, 2000.