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Center for Applied Toxinology

Grant number: 98/14307-9
Support type:Research Grants - Research, Innovation and Dissemination Centers - RIDC
Duration: October 01, 2000 - December 31, 2012
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Hugo Aguirre Armelin
Grantee:Hugo Aguirre Armelin
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Co-Principal Investigators:Ana Marisa Chudzinski-Tavassi ; Denise Vilarinho Tambourgi ; Eduardo Brandt de Oliveira ; Irina Kerkis ; Monica Valdyrce dos Anjos Lopes Ferreira ; Osvaldo Augusto Brazil Esteves Sant'Anna ; Raghuvir Krishnaswamy Arni ; Solange Maria de Toledo Serrano ; Tetsuo Yamane ; Yara Cury
Associated grant(s):12/00048-0 - Bothrops jararaca venom proteome rearrangement upon neonate to adult transition, PUB.ART
Associated scholarship(s):11/16623-1 - Proteomic analysis of the proteolytic activity of HF3, a metalloproteinase from the venom of Bothrops jararaca, upon human and snake plasma, BP.MS
11/05055-2 - Bothrops protease a (BPA): a new tool for the design of therapeutic agents for thrombosis and haemostasis, BP.MS
11/11308-0 - Proteomic analysis of leaves of sugarcane cultivars and genotypes, BP.DD
+ associated scholarships 11/08514-8 - Study of the degradome of HF3, a PIII-class snake venom metalloproteinase from Bothrops jararaca venom, on cultured fibroblasts, BP.PD
10/17328-0 - Comparative proteomic characterization of platelet aggregation induced by thrombin and PA-BJ, a serine proteinase from the venom of Bothrops jararaca, BP.DR
10/00206-0 - Molecular characterization of the hemorrhage induced by the metalloproteinase HF3: analysis of its interaction with extracellular matrix components and of the hemorrhagic tissue regeneration, BP.PD
08/09304-4 - Center for Applied Toxinology, BP.TT - associated scholarships

Abstract

The aim of the Interinstitutional Center for Applied Toxinology is to establish a world-class center for research into natural toxins. The Center will develop the study of toxins with the aim to investigate their potential therapeutic use, to foster contacts between science and industry and to raise the level of scientific human resources. The Institute Butantan with its history and tradition of work with venomous animals is uniquely positioned to serve as home for the Interinstitutional Center for Applied Toxinology. The underexplored variety of natural toxins in Brazil offers rich opportunities for exploitation in bioscience and biotechnology. Discoveries and findings stemming from the Center will be considered for patent registration and internal development or where appropriate for collaboration with or transfer to Brazilian and/or foreign enterprises. To these ends, the Center will act in the following areas: Research areas: - Toxins: isolation and characterization, development of bioassays and structural determination by NMR, mass spectrometry and X-ray crystallography; - Toxin gene analysis: cloning and expression; site-directed mutagenesis; - Therapy: development of immunological and pharmacological therapies; - Development of toxins for therapeutic use in a variety of diseases. Research will cover following areas: a) antihypertensive and vasodilator substances; b) anticoagulant factors; c) inflammation and pain; d) proteases; e) neurotoxins and f) enteric bacterial toxins. Educational aims: To improve and expand existing credited courses given on venomous animals, emphasizing the importance of biodiversity and its conservation; to include microorganisms, emphasizing hygiene and disease prevention; - To create professional MSc course in Venomous Animals; - To research classrooms of primary and secondary schools and colleges via the Internet. Technology Transfer: The Center will establish an INDUSTRIAL ASSOCIATES PROGRAM, with the aim of stimulating industrial participation in the Center's research activities. This Program will be open to all companies, regardless of size or nationality and the main objective will be to facilitate transfer of technology from academia to industry. The Center will industry with an access to much more comprehensive research than a typical small company could perform on its own. Membership will be open to all Brazilian companies and also to foreign companies with branches in the State Paulo. Ultimately, conserving biodiversity and arresting environmental degradation cannot be accomplished by international financial and packages alone but must involve the people through education and efforts at the grass roots level. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Thirty new molecules are discovered in snake venom 

Scientific publications (34)
(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)
XAVIER, CARLOS H.; MIRANDA, JOSE RODOLFO R.; YAMAGUCHI, JULIANA; DA SILVEIRA, KATIA D.; TEIXEIRA, MAURO M.; CHIANCA-, JR., DEOCLECIO ALVES; SIMOES E SILVA, ANA C.; SANTOS, ROBSON A. S.; CAMARGO, ANTONIO C. M.; IANZER, DANIELLE. Bj-PRO-5a and Bj-PRO 10c Found at C-Type Natriuretic Peptide Precursor of Bothrops jararaca Change Renal Function of Hypertensive Rats. INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS, v. 23, n. 3, p. 381-385, SEP 2017. Web of Science Citations: 1.
KOMEGAE, EVILIN NANAME; MATOZO SOUZA, TAIS APARECIDA; GRUND, LIDIANE ZITO; LIMA, CARLA; LOPES-FERREIRA, MONICA. Multiple functional therapeutic effects of TnP: A small stable synthetic peptide derived from fish venom in a mouse model of multiple sclerosis. PLoS One, v. 12, n. 2 FEB 24 2017. Web of Science Citations: 4.
BRESSAN, ELISANGELA; TOUSKA, FILIP; VETTER, IRINA; KISTNER, KATRIN; KICHKO, TATJANA I.; TEIXEIRA, NATHALIA B.; PICOLO, GISELE; CURY, YARA; LEWIS, RICHARD J.; FISCHER, MICHAEL J. M.; ZIMMERMANN, KATHARINA; REEH, PETER W. Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia. Pain, v. 157, n. 11, p. 2504-2516, NOV 2016. Web of Science Citations: 11.
ZELANIS, ANDRE; MENEZES, MILENE C.; KITANO, EDUARDO S.; LIBERATO, TARCISIO; TASHIMA, ALEXANDRE K.; PINTO, ANTONIO F. M.; SHERMAN, NICHOLAS E.; HO, PAULO L.; FOX, JAY W.; SERRANO, SOLANGE M. T. Proteomic identification of gender molecular markers in Bothrops jararaca venom. JOURNAL OF PROTEOMICS, v. 139, p. 26-37, APR 29 2016. Web of Science Citations: 18.
MORAIS, KATIA L. P.; FERNANDES PACHECO, MARIO THIEGO; BERRA, CAROLINA MARIA; BOSCH, ROSEMARY V.; SCIANI, JULIANA MOZER; CHAMMAS, ROGER; SAITO, RENATA DE FREITAS; IQBAL, ASIF; CHUDZINSKI-TAVASSI, ANA MARISA. Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell. Molecular and Cellular Biochemistry, v. 415, n. 1-2, p. 119-131, APR 2016. Web of Science Citations: 7.
CHUDZINSKI-TAVASSI, ANA MARISA; MORAIS, KATIA L. P.; FERNANDES PACHECO, MARIO THIEGO; MESQUITA PASQUALOTO, KERLY FERNANDA; DE SOUZA, JEAN GABRIEL. Tick salivary gland as potential natural source for the discovery of promising antitumor drug candidates. BIOMEDICINE & PHARMACOTHERAPY, v. 77, p. 14-19, FEB 2016. Web of Science Citations: 8.
PACHECO, MARIO T. F.; BERRA, CAROLINA M.; MORAIS, KATIA L. P.; SCIANI, JULIANA M.; BRANCO, VANIA G.; BOSCH, ROSEMARY V.; CHUDZINSKI-TAVASSI, ANA M. Dynein Function and Protein Clearance Changes in Tumor Cells Induced by a Kunitz-Type Molecule, Amblyomin-X. PLoS One, v. 9, n. 12 DEC 5 2014. Web of Science Citations: 13.
YAMASHIRO, EDSON T.; OLIVEIRA, ANA K.; KITANO, EDUARDO S.; MENEZES, MILENE C.; JUNQUEIRA-DE-AZEVEDO, INACIO L.; LEME, ADRIANA F. PAES; SERRANO, SOLANGE M. T. Proteoforms of the platelet-aggregating enzyme PA-BJ, a serine proteinase from Bothrops jararaca venom. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1844, n. 12, p. 2068-2076, DEC 2014. Web of Science Citations: 5.
LOPES-FERREIRA, MONICA; GOMES, EDUARDO MARTINS; BRUNI, FERNANDA MIRIANI; FERREIRA, MARCIO JOSE; CHARVET, PATRICIA; LIMA, CARLA. First report of interruption of mast cell degranulation and endothelial cells activation by anti-inflammatory drugs controlling the acute response provoked by Pseudoplatystoma fasciatum fish venom. Toxicon, v. 90, p. 237-248, NOV 2014. Web of Science Citations: 8.
ASEGA, AMANDA F.; OLIVEIRA, ANA K.; MENEZES, MILENE C.; NEVES-FERREIRA, ANA GISELE C.; SERRANO, SOLANGE M. T. Interaction of Bothrops jararaca venom metalloproteinases with protein inhibitors. Toxicon, v. 80, p. 1-8, MAR 15 2014. Web of Science Citations: 8.
LOPES-FERREIRA, MONICA; GRUND, LIDIANE ZITO; LIMA, CARLA. Thalassophryne nattereri fish venom: from the envenoming to the understanding of the immune system. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 20, p. 1-12, Set. 2014. Web of Science Citations: 11.
DIAS, GABRIELA S.; KITANO, EDUARDO S.; PAGOTTO, ANA H.; SANT'ANNA, SAVIO S.; ROCHA, MARISA M. T.; ZELANIS, ANDRE; SERRANO, SOLANGE M. T. Individual Variability in the Venom Proteome of Juvenile Bothrops jararaca Specimens. JOURNAL OF PROTEOME RESEARCH, v. 12, n. 10, p. 4585-4598, OCT 2013. Web of Science Citations: 27.
BRIGATTE, PATRICIA; KONNO, KATSUHIRO; GUTIERREZ, VANESSA PACCIARI; SAMPAIO, SANDRA COCCUZZO; ZAMBELLI, VANESSA OLZON; PICOLO, GISELE; CURI, RUI; CURY, YARA. Peripheral kappa and delta opioid receptors are involved in the antinociceptive effect of crotalphine in a rat model of cancer pain. Pharmacology Biochemistry and Behavior, v. 109, p. 1-7, AUG 2013. Web of Science Citations: 8.
KITANO, EDUARDO S.; GARCIA, THALITA C.; MENEZES, MILENE C.; TASHIMA, ALEXANDRE K.; ZELANIS, ANDRE; SERRANO, SOLANGE M. T. Cotiarinase is a novel prothrombin activator from the venom of Bothrops cotiara. Biochimie, v. 95, n. 8, p. 1655-1659, AUG 2013. Web of Science Citations: 6.
MARIA, DURVANEI AUGUSTO; DE SOUZA, JEAN GABRIEL; MORAIS, KATIA L. P.; BERRA, CAROLINA MARIA; ZAMPOLLI, HAMILTON DE CAMPOS; DEMASI, MARILENE; SIMONS, SIMONE MICHAELA; SAITO, RENATA DE FREITAS; CHAMMAS, ROGER; CHUDZINSKI-TAVASSI, ANA MARISA. A novel proteasome inhibitor acting in mitochondrial dysfunction, ER stress and ROS production. INVESTIGATIONAL NEW DRUGS, v. 31, n. 3, p. 493-505, JUN 2013. Web of Science Citations: 25.
FERREIRA DA SILVA, IGOR RAPP; LORENZETTI, RAQUEL; RENNO, ANDRE LISBOA; BALDISSERA, JR., LINEU; ZELANIS, ANDRE; DE TOLEDO SERRANO, SOLANGE MARIA; HYSLOP, STEPHEN. BJ-PI2, A non-hemorrhagic metalloproteinase from Bothrops jararaca snake venom. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1820, n. 11, p. 1809-1821, NOV 2012. Web of Science Citations: 14.
TASHIMA, ALEXANDRE K.; ZELANIS, ANDRE; KITANO, EDUARDO S.; IANZER, DANIELLE; MELO, ROBSON L.; RIOLI, VANESSA; SANT'ANNA, SAVIO S.; SCHENBERG, ANA C. G.; CAMARGO, ANTONIO C. M.; SERRANO, SOLANGE M. T. Peptidomics of Three Bothrops Snake Venoms: Insights Into the Molecular Diversification of Proteomes and Peptidomes. MOLECULAR & CELLULAR PROTEOMICS, v. 11, n. 11, p. 1245-1262, NOV 2012. Web of Science Citations: 47.
LOURENCO OLIVEIRA, DANIELLA GORETE; ALVAREZ-FLORES, MIRYAM PAOLA; LOPES, ADRIANA RIOS; CHUDZINSKI-TAVASSI, ANA MARISA. Functional characterisation of Vizottin, the first factor Xa inhibitor purified from the leech Haementeria vizottoi. THROMBOSIS AND HAEMOSTASIS, v. 108, n. 3, p. 570-578, SEP 2012. Web of Science Citations: 4.
PAES LEME, ADRIANA F.; SHERMAN, NICHOLAS E.; SMALLEY, DAVID M.; SIZUKUSA, LETICIA O.; OLIVEIRA, ANA K.; MENEZES, MILENE C.; FOX, JAY W.; SERRANO, SOLANGE M. T. Hemorrhagic Activity of HF3, a Snake Venom Metalloproteinase: Insights from the Proteomic Analysis of Mouse Skin and Blood Plasma. JOURNAL OF PROTEOME RESEARCH, v. 11, n. 1, p. 279-291, JAN 2012. Web of Science Citations: 31.
GUTIERREZ, VANESSA P.; ZAMBELLI, VANESSA O.; PICOLO, GISELE; CHACUR, MARUCIA; SAMPAIO, SANDRA C.; BRIGATTE, PATRICIA; KONNO, KATSUHIRO; CURY, YARA. The peripheral L-arginine-nitric oxide-cyclic GMP pathway and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine on neuropathic pain in rats. Behavioural Pharmacology, v. 23, n. 1, p. 14-24, 2012. Web of Science Citations: 18.
ZELANIS, ANDRE; TASHIMA, ALEXANDRE K.; PINTO, ANTONIO F. M.; LEME, ADRIANA F. PAES; STUGINSKI, DANIEL R.; FURTADO, MARIA F.; SHERMAN, NICHOLAS E.; HO, PAULO L.; FOX, JAY W.; SERRANO, SOLANGE M. T. Bothrops jararaca venom proteome rearrangement upon neonate to adult transition. PROTEOMICS, v. 11, n. 21, p. 4218-4228, NOV 2011. Web of Science Citations: 49.
MENEZES, MILENE C.; DE OLIVEIRA, ANA KARINA; MELO, ROBSON L.; LOPES-FERREIRA, MONICA; RIOLI, VANESSA; BALAN, ANDREA; PAES LEME, ADRIANA F.; SERRANO, SOLANGE M. T. Disintegrin-like/cysteine-rich domains of the reprolysin HF3: Site-directed mutagenesis reveals essential role of specific residues. Biochimie, v. 93, n. 2, p. 345-351, FEB 2011. Web of Science Citations: 14.
OLIVEIRA, ANA K.; LEME, ADRIANA F. PAES; ASEGA, AMANDA F.; CAMARGO, ANTONIO C. M.; FOX, JAY W.; SERRANO, SOLANGE M. T. New insights into the structural elements involved in the skin haemorrhage induced by snake venom metalloproteinases. THROMBOSIS AND HAEMOSTASIS, v. 104, n. 3, p. 485-497, SEP 2010. Web of Science Citations: 36.
ZELANIS, ANDRE; TASHIMA, ALEXANDRE K.; ROCHA, MARISA M. T.; FURTADO, MARIA F.; CAMARGO, ANTONIO C. M.; HO, PAULO L.; SERRANO, SOLANGE M. T. Analysis of the Ontogenetic Variation in the Venom Proteome/Peptidome of Bothrops jararaca Reveals Different Strategies to Deal with Prey. JOURNAL OF PROTEOME RESEARCH, v. 9, n. 5, p. 2278-2291, MAY 2010. Web of Science Citations: 73.
GUERREIRO, JULIANO R.; LAMEU, CLAUDIANA; OLIVEIRA, EDUARDO F.; KLITZKE, CLECIO F.; MELO, ROBSON L.; LINARES, EDLAINE; AUGUSTO, OHARA; FOX, JAY W.; LEBRUN, IVO; SERRANO, SOLANGE M. T.; CAMARGO, ANTONIO C. M. Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-hypertensive Peptide ROLE IN ARGININE AND NITRIC OXIDE PRODUCTION. Journal of Biological Chemistry, v. 284, n. 30, p. 20022-20033, JUL 24 2009. Web of Science Citations: 39.
OLIVEIRA, ANA K.; PAES LEME, ADRIANA F.; ASSAKURA, MARINA T.; MENEZES, MILENE C.; ZELANIS, ANDRE; TASHIMA, ALEXANDRE K.; LOPES-FERREIRA, MONICA; LIMA, CARLA; CAMARGO, ANTONIO C. M.; FOX, JAY W.; SERRANO, SOLANGE M. T. Simplified procedures for the isolation of HF3, bothropasin, disintegrin-like/cysteine-rich protein and a novel P-I metalloproteinase from Bothrops jararaca venom. Toxicon, v. 53, n. 7-8, p. 797-801, JUN 2009. Web of Science Citations: 22.
LEME‚ A.F.P.; KITANO‚ E.S.; FURTADO‚ M.F.; VALENTE‚ R.H.; CAMARGO‚ A.; HO‚ P.L.; FOX‚ J.W.; SERRANO‚ S.M.T. Analysis of the subproteomes of proteinases and heparin-binding toxins of eight Bothrops venoms. PROTEOMICS, v. 9, n. 3, p. 733-745, 2009.
MENEZES, MILENE C.; LEME, ADRIANA F. PAES; MELO, ROBSON L.; SILVA, CARLOS A.; DELLA CASA, MAISA; BRUNI, FERNANDA M.; LIMA, CARLA; LOPES-FERREIRA, MONICA; CAMARGO, ANTONIO C. M.; FOX, JAY W.; SERRANO, SOLANGE M. T. Activation of leukocyte rolling by the cysteine-rich domain and the hyper-variable region of HF3, a snake venom hemorrhagic metalloproteinase. FEBS Letters, v. 582, n. 28, p. 3915-3921, NOV 26 2008. Web of Science Citations: 22.
TASHIMA, ALEXANDRE K.; SANZ, LIBIA; CAMARGO, ANTONIO C. M.; SERRANO, SOLANGE M. T.; CALVETE, JUAN J. Snake venomics of the Brazilian pitvipers Bothrops cotiara and Bothrops fonsecai. Identification of taxonomy markers. JOURNAL OF PROTEOMICS, v. 71, n. 4, p. 473-485, OCT 7 2008. Web of Science Citations: 51.
SERRANO, SOLANGE M. T.; KIM, JUNHO; WANG, DEYU; DRAGULEV, BOJAN; SHANNON, JOHN D.; MANN, HENNING H.; VEIT, GUIDO; WAGENER, RAIMUND; KOCH, MANUEL; FOX, JAY W. The cysteine-rich domain of snake venom metalloproteinases is a ligand for von Willebrand factor A domains: role in substrate targeting. Journal of Biological Chemistry, v. 281, n. 52, p. 39746-39756, Dec. 2006.
MENEZES‚ M.C.; FURTADO‚ M.F.; TRAVAGLIA-CARDOSO‚ S.R.; CAMARGO‚ A.; SERRANO‚ S.M.T. Sex-based individual variation of snake venom proteome among eighteen Bothrops jararaca siblings. Toxicon, v. 47, n. 3, p. 304-312, 2006.
SILVA, CARLOS A.; ZULIANI, JULIANA P.; ASSAKURA, MARINA T.; MENTELE, REINHARD; CAMARGO, ANTONIO C. M.; TEIXEIRA, CATARINA F. P.; SERRANO, SOLANGE M. T. Activation of alpha(M)beta(2)-mediated phagocytosis by HF3, a P-III class metalloproteinase isolated from the venom of Bothrops jararaca. Biochemical and Biophysical Research Communications, v. 322, n. 3, p. 950-956, Sept. 2004.
ASSAKURA‚ M.T.; SILVA‚ C.A.; MENTELE‚ R.; CAMARGO‚ A.; SERRANO‚ S.M.T. Molecular cloning and expression of structural domains of bothropasin‚ a P-III metalloproteinase from the venom of Bothrops jararaca. Toxicon, v. 41, n. 2, p. 217-227, 2003.
CARNEIRO‚ S.M.; ASSAKURA‚ M.T.; BARRENCE‚ F.A.C.; CARDOSO‚ S.R.T.; DE MARTINS CAMARGO‚ A.C.; SESSO‚ A. Immunolocalization of venom metalloproteases in venom glands of adult and of newborn snakes of Bothrops jararaca. TISSUE & CELL, v. 34, n. 6, p. 381-389, 2002.

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