Centre of Excellence in New Target Discovery

• Grant number: 20/13139-0
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• Start date: October 01, 2021
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Agreement: GlaxoSmithKline
• Principal Investigator: Ana Marisa Chudzinski-Tavassi
• Grantee: Ana Marisa Chudzinski-Tavassi
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Host Companies: Secretaria da Saúde (São Paulo - Estado). Instituto Butantan; Glaxosmithkline Brasil Ltda
• City: Rio de JaneiroSão Paulo
• Pesquisadores principais: Denise Vilarinho Tambourgi ; Olga Celia Martinez Ibanez ; Vanessa Olzon Zambelli
• Associated researchers: Andrea Borrego ; Carla Cristina Squaiella ; Carlos Deocesano-Pereira ; Catarina de Fatima Pereira Teixeira ; Cristina Maria Fernandes ; Dilza Trevisan Silva ; Giselle Pidde Marques Porto ; Irina Kerkis ; José Ricardo Jensen ; Juliana Milani Scorisa Salgado ; Marcelo Medina de Souza ; Marcus Vinicius Buri ; Michelle Cristiane Búfalo ; Miryam Paola Alvarez Flores ; Nancy Starobinas ; Paula Cristiane Pohl ; Vanessa Olzon Zambelli
• Associated research grant(s): 25/02959-0 - Human-Induced Pluripotent Stem Cells (iPSCs) Differentiation Into Sensory Neurons for Screening Analgesic Compounds, AP.R SPRINT; 23/01532-8 - Neuroblastoma gene editing by CRISPR/Cas9 for target validation involved in pain and inflammation, AP.R
• Associated scholarship(s): 25/00619-8 - Implementation of a model for predicting skin lesions and necrotising lesions caused by Bothrops snake venom using Artificial Intelligence., BP.TT; 25/00998-9 - Effect of cytoprotective molecules on neurogenesis and neuroprotection processes in cell culture., BP.PD; 24/16580-0 - Validation of the antinociceptive effect of peptides extracted from animal venoms, BP.TT; + associated scholarships 24/10173-4 - Functional validation of the WW domain-containing protein 2 (WWPp2) as a molecular target for the treatment of osteoarthritis, BP.TT; 24/10065-7 - Validation of novel molecular targets from anti-inflammatory and cytoprotective molecules in neurons, BP.PD; 24/08724-2 - Implementation of a model for predicting phenotypes in chondrocytes using Artificial Intelligence., BP.TT; 24/06373-8 - Studies on poisons and derivatives: identification of molecular targets for the development of anti-inflammatory compounds, BP.PD; 24/00354-1 - Validation of the antinociceptive effect of peptides extracted from animal venoms, BP.TT; 23/12791-4 - Functional validation of molecular targets for the treatment of osteoarthritis in a model of chondrocytes treated with Pararama bristle extract, BP.TT; 23/13536-8 - Science dissemination and popularization content development, BP.TT; 22/16532-0 - Validation of novel molecular targets from anti-inflammatory and cytoprotective molecules in culture cells, BP.PD; 22/15071-0 - Implementation of a molecular biology platform for functional genomics by CRISPR/cas9 system, BP.PD; 22/01892-1 - New molecular targets identification and validation of anti-inflammatory peptides applying distinct mass spectrometry-based proteomics approaches, BP.PD - associated scholarships

Abstract

CENTD's focus is to combine the expertise of researchers at the Butantan Institute (biochemistry, OMICS, molecular and cellular biology, pharmacology, genetics, bioinformatics, immunology, and in vitro and in vivo assays) with GSK's experience in the search and validation of new targets related to immune-inflammatory diseases, to enable the design and development of new therapeutic agents. During the first 5 years, the CENTD team dedicated efforts to the implementation of 6 cell models that allowed the screening (screening) of 32 animal venoms, originating from different places in the world and 18 synthetic peptides, originated through computational analysis, from of proteins. Initially, the inflammatory potential of animal venoms and derived fractions was analyzed by screening in established cell models. Subsequently, the assays were optimized for the identification of anti-inflammatory activity and the samples were analyzed under these conditions. The analysis included high-content screening, multiplex, flow cytometry and mass spectrometry techniques. Transcriptomic, proteomic and bioinformatics analyzes were also performed, generating a very significant database. The screening proved to be effective, since of the 32 poisons analyzed, 3 were chosen for the next stages (target identification and validation). Likewise, of the 18 peptides studied, 5 were chosen for the follow-up of assays that seek to validate targets, using especially new technologies that will be implemented in the next stage. Also, the integration of data from different omic techniques, allowed, from tests with crude poison, the choice of 5 molecular targets for validation in the next step. In terms of disseminating science, several activities were developed by CENTD. Among them, exhibitions held in places of great circulation and visibility, such as subway stations and thermometers located at 300 addresses in São Paulo. According to the media, CENTD images have probably been viewed by more than 2 million people. In addition, entrepreneurial training was also offered by CENTD through the participation of the member group in the MBA - Health Innovation Management, in the organization of short courses and seminars, always focusing on innovation processes. During this period, 5 patents were applied at the INPI / PCT and 34 scientific articles were published. More than 50 masters and doctoral students, supervised by the main researchers (PIs), completed their theses and, more than 20 postdoctoral students, were supervised by the PIs. In addition, there is also the transfer of know-how between the main actors of the GSK project and the research groups coordinated by PIs (main researchers), composed of scientific progress meetings every two months, technical visits by GSK scientists to support the development of CENTD projects and annual visits by the advisory board. (AU)

Scientific publications

(12)

(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)

APOLINARIO, ALEXSANDRA CONCEICAO; SALATA, GIOVANNA CASSONE; DE SOUZA, MARCELO MEDINA; CHORILLI, MARLUS; LOPES, LUCIANA BIAGINI. Rethinking Breast Cancer Chemoprevention: Technological Advantages and Enhanced Performance of a Nanoethosomal-Based Hydrogel for Topical Administration of Fenretinide. AAPS PHARMSCITECH, v. 23, n. 4, p. 14-pg., 2022-04-05. (18/13877-1, 14/50928-2, 20/13139-0, 18/14375-0)

DE MELO, THATIANA CORREA; TREVISAN-SILVA, DILZA; ALVAREZ-FLORES, MIRYAM P.; GOMES, RENATA NASCIMENTO; DE SOUZA, MARCELO MEDINA; VALERIO, HELLEN PAULA; OLIVEIRA, DOUGLAS S.; DEOCESANO-PEREIRA, CARLOS; BOTOSSO, VIVIANE FONGARO; CALIL JORGE, SORAIA ATTIE; et al. Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 18, p. 17-pg., 2022-09-01. (20/10847-4, 20/05293-0, 20/13139-0)

ALVAREZ-FLORES, MIRYAM PAOLA; BATISTA, ISABEL DE FATIMA CORREIA; BOAS, ISADORA MARIA VILLAS; BUFALO, MICHELLE CRISTIANE; DE SOUZA, JEAN GABRIEL; OLIVEIRA, DOUGLAS SOUZA; BONFA, GIULIANO; FERNANDES, CRISTINA MARIA; PORTO, RAFAEL MARQUES; LICHTENSTEIN, FLAVIO; et al. Snake and arthropod venoms: Search for inflammatory activity in human cells involved in joint diseases. Toxicon, v. 238, p. 14-pg., 2023-12-27. (16/12128-0, 20/13139-0, 17/07009-4, 17/06736-0, 15/50040-4)

POHL, PAULA C.; VILLAS-BOAS, ISADORA M.; PIDDE, GISELLE; TAMBOURGI, DENISE V.. Pararamosis, a Neglected Tropical Disease Induced by Premolis semirufa Caterpillar Toxins: Investigating Their Effects on Synovial Cell Inflammation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 25, n. 23, p. 17-pg., 2024-12-01. (15/50040-4, 20/13139-0)

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)

BORREGO, ANDREA; COLOMBO, FRANCESCA; DE SOUZA, JEAN GABRIEL; JENSEN, JOSE RICARDO; DASSANO, ALICE; PIAZZA, ROCCO; RODRIGUES DOS SANTOS, BARBARA ANAIS; RIBEIRO, ORLANDO GARCIA; DE FRANCO, MARCELO; KOURY CABRERA, WAFA HANNA; et al. Pycard and BC017158 Candidate Genes of Irm1 Locus Modulate Inflammasome Activation for IL-1 beta Production. FRONTIERS IN IMMUNOLOGY, v. 13, p. 16-pg., 2022-06-21. (17/06736-0, 20/13139-0)

MORAIS, K. L. P.; CICCONE, L.; STURA, E.; ALVAREZ-FLORES, M. P.; MOURIER, G.; DRIESSCHE, M. VANDEN; SCIANI, J. M.; IQBAL, A.; KALIL, S. P.; PEREIRA, G. J.; et al. Structural and functional properties of the Kunitz-type and C-terminal domains of Amblyomin-X supporting its antitumor activity. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 10, p. 16-pg., 2023-02-09. (15/50040-4, 20/13139-0, 13/07467-1)

HOSCH, NATALIA G.; MARTINS, BARBARA B.; ALCANTARA, QUEREN A.; BUFALO, MICHELLE CRISTIANE; NETO, BEATRIZ S.; CHUDZINKI-TAVASSI, ANA MARISA; SANTA-CECILIA, FLAVIA V.; CURY, YARA; ZAMBELLI, VANESSA O.. Wnt signaling is involved in crotalphine-induced analgesia in a rat model of neuropathic pain. European Journal of Pharmacology, v. 959, p. 13-pg., 2023-10-01. (20/04998-0, 15/50040-4, 13/07467-1, 20/13139-0)

LOBBA, ALINE R. M.; ALVAREZ-FLORES, MIRYAM PAOLA; FESSEL, MELISSA REGINA; BURI, MARCUS VINICIUS; OLIVEIRA, DOUGLAS S. S.; GOMES, RENATA N. N.; CUNEGUNDES, PRISCILA S. S.; DEOCESANO-PEREIRA, CARLOS; CINEL, VICTOR D. D.; CHUDZINSKI-TAVASSI, ANA M. M.. A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 9, p. 16-pg., 2022-08-16. (20/13139-0, 18/20469-7, 13/07467-1, 18/10937-3, 15/50040-4)

DE LIMA, CINTHYA LAIS; POHL, PAULA C.; VILLAS-BOAS, ISADORA M.; PIDDE, GISELLE; TAMBOURGI, DENISE V.. Investigating the impact of Premolis semirufa caterpillar bristle toxins on human chondrocyte activation and inflammation. PLoS Neglected Tropical Diseases, v. 19, n. 2, p. 19-pg., 2025-02-01. (15/50040-4, 13/07467-1, 20/13139-0)

ALVAREZ, ANGELA MARIA; TRUFEN, CARLOS EDUARDO MADUREIRA; BURI, MARCUS VINICIUS; DE SOUSA, MARCELA BEGO NERING; ARRUDA-ALVES, FRANCISCO IVANIO; LICHTENSTEIN, FLAVIO; CASTRO DE OLIVEIRA, URSULA; JUNQUEIRA-DE-AZEVEDO, INACIO DE LOIOLA MEIRELLES; TEIXEIRA, CATARINA; MOREIRA, VANESSA. Tumor Necrosis Factor-Alpha Modulates Expression of Genes Involved in Cytokines and Chemokine Pathways in Proliferative Myoblast Cells. CELLS, v. 13, n. 13, p. 19-pg., 2024-07-01. (20/13139-0, 15/50040-4, 15/25437-8, 18/10937-3)

BURI, MARCUS VINICIUS; GARAVELLI, GRACIANA YOKOTA; VIGERELLI, HUGO; DE SOUZA, MARCELO MEDINA; MAIA LOBBA, ALINE RAMOS; GHIDELLI-DISSE, SONJA; CHUDZINSKI-TAVASSI, ANA MARISA. cAmbly: A non-toxic cell-penetrating peptide derived from Amblyomin-X with targeted delivery to mitochondrial and cytoplasmic proteins. PLoS One, v. 20, n. 3, p. 14-pg., 2025-03-12. (15/50040-4, 20/13139-0, 13/07467-1)