INSTITUTO DE CIÊNCIAS BIOMÉDICAS

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Excelência em Ensino e Pesquisa

Biologia Molecular da Glândula Tiróide

Coordenadora

Edna Teruko Kimura 

 

Alunos de pós-graduação

Sílvia Emiko Matsuo

Luciane Martins

Suzana Garcia Leoni

Júlio Cezar Marques Ricarte Filho

 

Alunos de Iniciação Científica

 Kátia Naomi Ebina

Fabiana Yamauti Gimenes

           

LINHAS DE PESQUISA  

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

SUMÁRIO DOS PROJETOS DE PESQUISA EM ANDAMENTO

 O câncer de tiróide é a neoplasia mais freqüente do sistema endócrino. Nosso laboratório investiga os eventos moleculares que regulam a oncogênese da célula folicular tiroidiana, do bócio ao câncer. Utilizamos técnicas de biologia celular e molecular como Real Time-PCR, Imuno-histoquímica, expressão condicional de oncogenes, interferência de RNA e Serial Analysis of Gene Expression (SAGE) para elucidar:

  • Os efeitos da expressão condicional de oncogenes na proliferação e apoptose das células foliculares tiroidianas
  • Como a família de TGF-b (TGF-b e Activina) e seu sistema de sinalização contribuem para a patogênese do bócio e do câncer de tiróide
  • A função da mutação de BRAF no câncer de tiróide
  • A função de galectina-3 na progressão tumoral da tiróide
  • O papel de IGF e IGFBP em diferentes modelos experimentais: tiróide, fígado e cartilagem condilar

Participação em Projetos Genomas

 ·          Genoma Humano do Câncer: http://watson.fapesp.br/onsa/Genoma3.htm

    AEG (Agronomical & Environmental Genomes): http://aeg.lbi.ic.unicamp.br/aeg/aeg.html

Xylella fastidiosa

v     Leifsonia xyli

v     Leptospira interrogans

v     Eucaliptus grandis

v     Coffee arábica

v     Bos indicus

 

·          TFI (Transcript Finishing Initiative): http://watson.fapesp.br/onsa/Genoma3.htm

 

FAPESP logo

                                                                      (  www.fapesp.br  )

PUBLICAÇÕES

  •    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, in press, 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

  •   Christoffolete MA, Linardi CC, de Jesus L, Ebina KN, Carvalho SD, Ribeiro MO, Rabelo R, Curcio C, Martins LKimura ET, Bianco AC. Mice with targeted disruption of the Dio2 gene have cold-induced erexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis Diabetes. 53:577-84, 2004

  •   Matsuo SEMartins LLeoni SG, Hajjar D, Ricarte-Filho JCMEbina KNKimura ET. Marcadores Biológicos de tumores tiroidianos. Arq Bras Endocrinol Metab 48: 114-125, 2004.

  •    Affonso-Jr RJ, Oshima CTF, Kimura ET, Silva MRR, Egami MI, Segreto RA, Segreto HRC. Expressão da Proteína TGFba em coração irradiado in vivo. Radiol Bras 37:107-113, 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 E, 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.

  •    Hajjar D, Santos MF, Kimura ETMechanical stress induced by propulsive appliance stimulates the synthesis of insulin-like growth factors I and II (IGF-I and IGF-II) in the mandibular condylar cartilage. Arch Oral Biol 48, 635-42, 2003.

  •    Cerutti JM, Ebina KNMatsuo SEMartins L, Maciel RM, Kimura ET. Expression 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 SEEbina KN, Friguglietti C, Kulcsar MA, Kimura ET. Activin bB expression in rat experimental goiter and human thyroid tumors. Thyroid 13:239-47, 2003.

  •    Mattos MD, Kimura ET, Silva MR, Egami MI, Segreto RA, Segreto HR. Latent TGFbeta1 activation in the lung irradiated in vivo.Rev Asso Med Bras, 48(4): 329-334, 2002.

  •   Segreto HR, Ferreira AT, Kimura ET, Franco M, Egami MI, Silva MR, Segreto RA. Amifostine does not prevent activation of TGFbeta1 but induces smad 7 activation in megakaryocytes irradiated in vivo. Am J Hematol, 71(3):143-51, 2002.

  •    Martins LMatsuo SEEbina 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.

  •    Sousa AB, Soto-Blanco, Guerra JL, Kimura ET, Góniak SL. Does prologued oral exposure to cyanide promote hepatotoxicity and nefrotoxicity? Toxicology, 174:87-95, 2002.

  • ·  Soto-Blanco B, Gorniak SL, Kimura ETPhysiological effects of chronic cyanide administration to growing goats – a model for cyanogenic plants. Veterin Res Commun, 25:379-389, 2001.

  •    Villar RC, Egami ML, Silva MRR, Kimura ET, Segreto RA, Segreto HRC. In vivo radioprotection of mouse bone marrow: protection from apoptotic death by WR-2721. Braz J Morphol Sci, 16:1-5, 1999.

  •    Kimura ET, Kopp P, Zbaeren J, Asmis LM, Ruchti C, Maciel RMB, Studer H. Expression of transforming growth factor beta (TGFbeta) 1, 2 and 3 in benign and malignant human thyroid tumors: a comparative study”. Thyroid, 9:119-125, 1999.

  •    Asmis LM, Kaempf J, Von Gruenigen C, Kimura ET, Wagner HE, Studer H. Acquired and naturally occurring resistance of thyroid follicular cells to the growth inhibitory action of transforming growth factor-beta 1 (TGF-beta 1). J Endocrinol,149(3):485-96, 1996.

  •    Maciel RM, Kimura ET, Takahaski MH, Lopes MH, Mesquita MI, Moses AC, Alberti VN. Insulin-Like Growth Factor I in Human Thyroid Tissue: Specific Localization by Immunohistochemistry and In Situ Hybridization. Endocr Pathol Autumn, 6(3):207-215, 1995.

  •   Kopp P, Kimura ET, Aeschimann S, Oestreicher M, Tobler A, Fey MF, Studer H. Polyclonal and monoclonal thyroid nodules coexist within human multinodular goiters. J Clin Endocrinol Metab, 79(1):134-9, 1994.

  •   Aeschimann S, Kopp PA, Kimura ET, Zbaeren J, Tobler A, Fey MF, Studer H. Morphological and functional polymorphism within clonal thyroid nodules. J Clin Endocrinol Metab, 77(3):846-51, 1993.

  •   Carvalho SD, Kimura ET, Bianco AC, Silva JE. Central role of brown adipose tissue thyroxine 5′-deiodinase on thyroid hormone-dependent thermogenic response to cold. Endocrinology,128(4):2149-59, 1991.

 

PUBLICAÇÕES GENOMA

  •    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 SGMatsuo SEKimura 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 ETLeoni 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 ETet 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 fastidiosaJ Bacteriol, 185:1018-26, 2003.

  •    Kimura ET, Baía GS. Rede ONSA e o Projeto Genoma do Câncer: Contribuições ao Genoma Humano. Arq Bras Endocrinol Metab, 46: 325-329, 2002.

  •    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, 9812103-12108, 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.