Rational approach for searching molecular targets involved in inflammatory events and cell survival

• Grant number: 15/50040-4
• Support type: Research Grants - Research Centers in Engineering Program
• Duration: December 01, 2015 - December 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Cooperation agreement: GlaxoSmithKline
• Principal researcher: Ana Marisa Chudzinski-Tavassi
• Grantee: Ana Marisa Chudzinski-Tavassi
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Company: Glaxosmithkline Brasil Ltda
• Pesquisadores principais:( Atuais ): Catarina de Fatima Pereira Teixeira ; Denise Vilarinho Tambourgi ; Irina Kerkis ; Olga Celia Martinez Ibanez
• Pesquisadores principais:( Anteriores ): Yara Cury
• Associated grant(s): 18/08434-3 - Drug discovery targeting polyglutamylation in neurodegenerative disorders, AP.R SPRINT; 20/05293-0 - Human cells infection by coronavirus (SARS-CoV2) : search for therapeutic strategies, AP.R; 16/19176-0 - Multi-User Equipment approved in grant 15/50040-4: micro confocal high-content imaging system, AP.EMU; + associated grants 16/19391-8 - Multi-user equipment approved in grant 15/50040-4: microscopy confocal TCS SP8 DLS Hyvolution, AP.EMU; 16/06027-6 - Multi-user equipment: acquisition of Amnis image stream to flow cytometry with image, AP.EMU; 16/06026-0 - Multi-User Equipment: QExactive Plus acquisition, thermo scientific for mass spectrometry, AP.EMU - associated grants
• Associated scholarship(s): 19/09498-8 - Signaling pathways involved in the inflammatory response in cellular osteoarthritis models, BP.PD; 18/20677-9 - Equine tumor: proteomic analysis, BP.PD; 18/20469-7 - Several studies have shown that chondrocyte aging is associated with the degeneration of articular cartilage, and can be observed in joint diseases pathogenesis, such as rheumatoid arthritis and osteoarthritis (OA). one of the most prominent changes in, BP.PD; + associated scholarships 18/20998-0 - Analysis of digitized results from transcriptomics and proteomics experiments developed in CENTD, BP.PD; 18/10937-3 - Satellite cells: effects of lipocalin, hemolin and derived peptides on proliferation and differentiation of quiescent skeletal muscle cells, BP.PD; 18/01370-0 - Investigation of the action of toxins in osteoclastogenesis and in lymphocytes activation: search of possible therapeutic targets, BP.PD; 17/19733-9 - Study of the effects of an ofidian metalloproteinase in preadipocytes: activation of inflammatory response and cell differentiation, BP.MS; 17/07009-4 - Signaling pathways involved in inflammatory response in osteoarthritis 3D culture models, BP.PD; 17/06736-0 - Identification/elucidation and validation of new targets/pathways involved in osteoarthritis, BP.PD; 16/11965-5 - Therapeutic epigenomic targets: MiRNA profile in an in vitro model of osteoarthritis treated with rLosac (PD-1), BP.PD; 16/12128-0 - Pain in arthritis molecular mechanisms: identification of new targets for drug development, BP.PD; 16/10886-4 - Toxins isolated from animal venoms acting on glycation of in vitro osteoarthritis model extracellular matrix , BP.PD; 16/13588-4 - Revisiting cDNA libraries, BP.PD - associated scholarships
• FAPESP publication: https://media.fapesp.br/bv/uploads/pdfs/fapesp_uk_o8j4cK8_178_178.pdf

Abstract

Successful drug development requires a disease target that plays a vital role in the causation and/or progression of the disease phenotype and that can be modulated with a drug molecule. In other words, therapeutically relevant targets are both “disease-modifying” and “druggable”. It has been estimated that around 10% of the entire human genome is involved in disease onset or progression, resulting in approximately 3000 potential targets suitable for therapeutic intervention. Thus, the rapid and reliable identification of the most promising targets for drug discovery efforts would be the major challenge for the pharmaceutical industry. Moreover, the knowledge of the mechanisms that govern the inflammatory process and cell survival, generated by basic research, is essential for the identification and validation of potential and more specific molecular target. Natural products are a rich source of biologically active compounds. Many of today’s medicines are either obtained directly from a natural source or were developed from a lead compound originally obtained from a natural source. Venoms and toxins from animals, plants, snakes, spiders, scorpions, insects, slugs, and microorganisms are extremely potent because the often have very specific interactions with a macromolecular target in the body. As a result, they have proved to be important not only as lead compounds in the development of novel drugs, but also as tools in studying receptors, ion channels, and enzymes. In our research group, interesting bioactive molecules from animal venoms and secretions, such as proteins (wild or recombinant form) and derived-peptides, targeting the homeostatic system and inflammatory events, have been exploited and are in different phases of development. We have been focusing our efforts on understanding their mechanism of action through the exploitation of specific signaling pathways in order to identify and validate novel molecular targets. Among the proteins’ families taken into account are lipocalins, hemolins, serine protease inhibitors, phospholipases and chaperones. In this regard, the main idea is to consider the expertise of the Butantan Institute researchers already have in computer-aided molecular design/bioinformatics/OMICS (transcriptome, proteome) field, molecular and cellular biology and immunology approaches (in vitro assays), and in vivo models and image techniques in order to create a Center of Excellence for Research in Target Discovery. (AU)

Scientific publications

(27)

(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)

VILLAS-BOAS, ISADORA MARIA; BONFA, GIULIANO; TAMBOURGI, DENISE V.. Venomous caterpillars: From inoculation apparatus to venom composition and envenomation. Toxicon, v. 153, p. 39-52, OCT 2018. (15/50040-4, 17/07009-4, 13/50158-0)

BOSCH, ROSEMARY VIOLA; ALVAREZ-FLORES, MIRYAM PAOLA; MARIA, DURVANEI AUGUSTO; CHUDZINSKI-TAVASSI, ANA MARISA. Hemolin triggers cell survival on fibroblasts in response to serum deprivation by inhibition of apoptosis. BIOMEDICINE & PHARMACOTHERAPY, v. 82, p. 537-546, AUG 2016. (13/07467-1, 13/06892-0, 15/50040-4)

BUFALO, MICHELLE CRISTIANE; DE ALMEIDA, MAIRA ESTANISLAU SOARES; JENSEN, JOSE RICARDO; DEOCESANO-PEREIRA, CARLOS; LICHTENSTEIN, FLAVIO; PICOLO, GISELE; CHUDZINSKI-TAVASSI, ANA MARISA; SAMPAIO, SANDRA COCCUZZO; CURY, YARA; ZAMBELLI, VANESSA OLZON. uman Sensory Neuron-like Cells and Glycated Collagen Matrix as a Model for the Screening of Analgesic Compound. CELLS, v. 11, n. 2, JAN 2022. (15/50040-4, 20/13139-0)

MAMBELLI-LISBOA, NICOLE CAROLINE; SCIANI, JULIANA MOZER; BRANDAO PRIETO DA SILVA, ALVARO ROSSAN; KERKIS, IRINA. Co-Localization of Crotamine with Internal Membranes and Accentuated Accumulation in Tumor Cells. Molecules, v. 23, n. 4, APR 2018. (15/50040-4)

CAMARA, GUILHERME A.; NISHIYAMA-JR, MILTON Y.; KITANO, EDUARDO S.; OLIVEIRA, URSULA C.; DA SILVA, JR., PEDRO I.; JUNQUEIRA-DE-AZEVEDO, INACIO L.; TASHIMA, ALEXANDRE K.. A Multiomics Approach Unravels New Toxins With PossibleIn SilicoAntimicrobial, Antiviral, and Antitumoral Activities in the Venom ofAcanthoscurria rondoniae. FRONTIERS IN PHARMACOLOGY, v. 11, JUL 17 2020. (17/21052-0, 15/50040-4)

JANOVITS, PRISCILA MOTTA; LEIGUEZ, ELBIO; PORTAS, VIVIANE; TEIXEIRA, CATARINA. A Metalloproteinase Induces an Inflammatory Response in Preadipocytes with the Activation of COX Signalling Pathways and Participation of Endogenous Phospholipases A(2). BIOMOLECULES, v. 11, n. 7, JUL 2021. (15/50040-4)

VIANA, MARIANA N.; LEIGUEZ, ELBIO; GUTIERREZ, JOSE M.; RUCAVADO, ALEXANDRA; MARKUS, REGINA P.; MARCOLA, MARINA; TEIXEIRA, CATARINA; FERNANDES, CRISTINA M.. A representative metalloprotease induces PGE(2) synthesis in fibroblast-like synoviocytes via the NF-kappa B/COX-2 pathway with amplification by IL-1 beta and the EP4 receptor. SCIENTIFIC REPORTS, v. 10, n. 1, FEB 24 2020. (15/50040-4)

ZULIM DE CARVALHO, ANA EDUARDA; GIANNOTTI, KARINA; LEIGUEZ JUNIOR, ELBIO; MATSUBARA, MARCIO; DOS SANTOS, MARIA CRISTINA; FORTES-DIAS, CONSUELO LATORRE; TEIXEIRA, CATARINA. Crotalus durissus ruruima Snake Venom and a Phospholipase A(2) Isolated from This Venom Elicit Macrophages to Form Lipid Droplets and Synthesize Inflammatory Lipid Mediators. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2019, NOV 4 2019. (15/24701-3, 14/18549-1, 18/05637-0, 15/50040-4)

KERKIS, IRINA; DE BRANDO PRIETO DA SILVA, ALVARO ROSSAN; POMPEIA, CELINE; TYTGAT, JAN; DE SA JUNIOR, PAULO L.. Toxin bioportides: exploring toxin biological activity and multifunctionality. CELLULAR AND MOLECULAR LIFE SCIENCES, v. 74, n. 4, p. 647-661, FEB 2017. (15/50040-4)

ARRUDA, GIAN LUCAS M.; VIGERELLI, HUGO; BUFALO, MICHELLE C.; LONGATO, GIOVANNA B.; VELOSO, RODINEI V.; ZAMBELLI, VANESSA O.; PICOLO, GISELE; CURY, YARA; MORANDINI, ANDRE C.; MARQUES, ANTONIO CARLOS; et al. Box Jellyfish (Cnidaria, Cubozoa) Extract Increases Neuron's Connection: A Possible Neuroprotector Effect. BIOMED RESEARCH INTERNATIONAL, v. 2021, MAR 5 2021. (15/21007-9, 15/50040-4, 16/06137-6, 19/19929-6, 13/07467-1, 11/50242-5)

IQBAL, ASIF; GOLDFEDER, MAURICIO BARBUGIANI; MARQUES-PORTO, RAFAEL; ASIF, HUMA; DE SOUZA, JEAN GABRIEL; FARIA, FERNANDA; CHUDZINSKI-TAVASSI, ANA MARISA. Revisiting antithrombotic therapeutics; sculptin, a novel specific, competitive, reversible, scissile and tight binding inhibitor of thrombin. SCIENTIFIC REPORTS, v. 7, MAY 3 2017. (13/07467-1, 15/50040-4)

BRANCO, VANIA G.; IQBAL, ASIF; ALVAREZ-FLORES, MIRYAM P.; SCIANI, JULIANA M.; DE ANDRADE, SONIA A.; IWAI, LEO K.; SERRANO, SOLANGE M. T.; CHUDZINSKI-TAVASSI, ANA M.. Amblyomin-X having a Kunitz-type homologous domain, is a noncompetitive inhibitor of FXa and induces anticoagulation in vitro and in vivo. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1864, n. 10, p. 1428-1435, OCT 2016. (13/07467-1, 15/50040-4)

BUFALO, MICHELLE C.; ALMEIDA, MAIRA E.; FRANCA, ISABELLA ARAUJO; ZAMBELLI, VANESSA O.; SANT'ANNA, MORENA BRAZIL MARTINS; KIMURA, LOUISE F.; GIARDINI, ALINE CAROLINA; CURY, YARA; SAMPAIO, SANDRA COCCUZZO. Advanced glycation endproducts produced by in vitro glycation of type I collagen modulate the functional and secretory behavior of dorsal root ganglion cells cultivated in two-dimensional system. Experimental Cell Research, v. 382, n. 2-3, SEP 15 2019. (16/12128-0, 15/50040-4, 12/51241-5, 16/10886-4)

DE SOUZA, JEAN GABRIEL; MORAIS, KATIA L. P.; ANGLES-CANO, EDUARDO; BOUFLEUR, PAMELA; DE MELLO, EVANDRO SOBROZA; MARIA, DURVANEI AUGUSTO; TAEMI ORIGASSA, CLARICE SILVIA; ZAMPOLLI, HAMILTON DE CAMPOS; SARAIVA CAMARA, NIELS OLSEN; BERRA, CAROLINA MARIA; et al. Promising pharmacological profile of a Kunitz-type inhibitor in murine renal cell carcinoma model. ONCOTARGET, v. 7, n. 38, p. 62255-62266, SEP 20 2016. (12/06944-8, 12/02270-2, 10/07958-7, 15/50040-4, 13/07467-1)

ALVAREZ-FLORES, MILYAM P.; HEBERT, AUDREY; GOUELLE, CATHY; GELLER, SARAH; CHUDZINSKI-TAVASSI, ANA M.; PELLERIN, LUC. Neuroprotective effect of rLosac on supplement-deprived mouse cultured cortical neurons involves maintenance of monocarboxylate transporter MCT2 protein levels. Journal of Neurochemistry, v. 148, n. 1, p. 80-96, JAN 2019. (13/07467-1, 15/50040-4)

D'AMELIO, FERNANDA; VIGERELLI, HUGO; PRIETO-DA-SILVA, ALVARO ROSSAN DE BRANDAO; OSORIO FRARE, EDUARDO; BATISTA, ISABEL DE FATIMA CORREIA; PIMENTA, DANIEL CARVALHO; KERKIS, IRINA. Bothrops moojeni Venom and Its Components Strongly Affect Osteoclasts' Maturation and Protein Patterns. TOXINS, v. 13, n. 7, JUL 2021. (15/50040-4)

OLIVEIRA, DOUGLAS SOUZA; DE SOUZA, JEAN GABRIEL; ALVAREZ-FLORES, MIRYAM PAOLA; CUNEGUNDES, PRISCILA S.; DEOCESANO-PEREIRA, CARLOS; LOBBA, ALINE MAIA; GOMES, RENATA N.; CHUDZINSKI-TAVASSI, ANA MARISA. Lonomia obliqua Venom Induces NF-kappa B Activation and a Pro-Inflammatory Profile in THP-1-Derived Macrophage. TOXINS, v. 13, n. 7, JUL 2021. (15/50040-4, 13/07467-1)

LICHTENSTEIN, FLAVIO; IQBAL, ASIF; ALVES DE LIMA WILL, SONIA ELISABETE; BOSCH, ROSEMARY VIOLA; DEOCESANO-PEREIRA, CARLOS; GOLDFEDER, MAURICIO BARBUGIANI; CHAMMAS, ROGER; MADUREIRA TRUFEN, CARLOS EDUARDO; PEREIRA MORAIS, KATIA LUCIANO; DE SOUZA, JEAN GABRIEL; et al. Modulation of stress and immune response by Amblyomin-X results in tumor cell death in a horse melanoma model. SCIENTIFIC REPORTS, v. 10, n. 1, APR 14 2020. (16/13588-4, 13/07467-1, 15/50040-4, 17/02052-9)

SCHMIDT, MARIANA COSTA BRAGA; MORAIS, KATIA L. P.; DE ALMEIDA, MAIRA ESTANISLAU SOARES; IQBAL, ASIF; GOLDFEDER, MAURICIO BARBUGIANI; CHUDZINSKI-TAVASSI, ANA MARISA. Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells. CELL ADHESION & MIGRATION, v. 14, n. 1, p. 129-138, JAN 1 2020. (13/07467-1, 14/24512-3, 15/50040-4)

ALVAREZ, ANGELA M.; DEOCESANO-PEREIRA, CARLOS; TEIXEIRA, CATARINA; MOREIRA, VANESSA. IL-1 beta and TNF-alpha Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved. CELLS, v. 9, n. 9, SEP 2020. (15/50040-4, 18/10937-3)

MONTONI, FABIO; ANDREOTTI, DIANA ZUKAS; DOS SANTOS EICHLER, ROSANGELA APARECIDA; SANTOS, WELLINGTON DA SILVA; KISAKI, CAROLINA YUKIKO; SUEHIRO ARCOS, STEPHANIE SANTOS; LIMA, ISMAEL FEITOSA; MALTAURO SOARES, MAGNA APARECIDA; NISHIYAMA-JR, MILTON YUTAKA; NAVA-RODRIGUES, DANIEL; et al. The impact of rattlesnake venom on mice cerebellum proteomics points to synaptic inhibition and tissue damage. JOURNAL OF PROTEOMICS, v. 221, JUN 15 2020. (17/17943-6, 13/07467-1, 16/04000-3, 15/50040-4, 17/06496-9)

TEIXEIRA, CATARINA; FERNANDES, CRISTINA MARIA; LEIGUEZ, ELBIO; CHUDZINSKI-TAVASSI, ANA MARISA. Inflammation Induced by Platelet-Activating Viperid Snake Venoms: Perspectives on Thromboinflammation. FRONTIERS IN IMMUNOLOGY, v. 10, SEP 4 2019. (15/24701-3, 15/50040-4)

DE SOUZA, JEAN GABRIEL; STAROBINAS, NANCY; IBANEZ, OLGA CELIA MARTINEZ. Unknown/enigmatic functions of extracellular ASC. IMMUNOLOGY, v. 163, n. 4, p. 377-388, AUG 2021. (19/20713-8, 15/50040-4, 17/06736-0)

PIDDE, GISELLE; NISHIYAMA, MILTON Y.; DE OLIVEIRA, URSULA CASTRO; VILLAS-BOAS, ISADORA M.; PAES-LEME, ADRIANA F.; JUNQUEIRA-DE-AZEVEDO, INACIO L.; MARQUES-PORTO, RAFAEL; SQUAIELLA-BAPTISTAO, CARLA C.; TAMBOURGI, DENISE V.. Integrative multiomics analysis of Premolis semirufa caterpillar venom in the search for molecules leading to a joint disease. SCIENTIFIC REPORTS, v. 11, n. 1, JAN 21 2021. (13/07467-1, 15/50040-4)

DEOCESANO-PEREIRA, CARLOS; MACHADO, RAQUEL A. C.; CHUDZINSKI-TAVASSI, ANA MARISA; SOGAYAR, MARI CLEIDE. Emerging Roles and Potential Applications of Non-Coding RNAs in Glioblastoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 7, APR 2020. (15/50040-4, 16/05311-2)

MAMBELLI-LISBOA, NICOLE C.; FRARE, EDUARDO O.; DA COSTA-NEVES, ADRIANA; PRIETO DA SILVA, ALVARO R. B.; KERKIS, IRINA. Murine osteoclastogenesis suppression using conditioned media produced by melanoma or activated and non-activated Jurkat-E6 cells. Cell Biology International, v. 44, n. 5, p. 1184-1192, MAY 2020. (15/50040-4)

MARIANO, DOUGLAS O. C.; PREZOTTO-NETO, JOSE PEDRO; SPENCER, PATRICK J.; SCIANI, JULIANA MOZER; PIMENTA, DANIEL C.. Proteomic analysis of soluble proteins retrieved from Duttaphrynus melanostictus skin secretion by IEx-batch sample preparation. JOURNAL OF PROTEOMICS, v. 209, OCT 30 2019. (15/50040-4)