Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets

• Grant number: 18/20403-6
• Support Opportunities: Research Projects - Thematic Grants
• Duration: June 01, 2019 - May 31, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Vera Luiza Capelozzi
• Grantee: Vera Luiza Capelozzi
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Edwin Roger Parra Cuentas ; Lisete Ribeiro Teixeira ; Patricia Rieken Macedo Rocco ; Pedro Leme Silva
• Associated scholarship(s): 22/06510-0 - Study of immunocellular and immunobiological profiles as emerging predictive and prognostic markers for malignant mesothelioma, BP.IC; 21/05917-6 - QuaMN-Ki study: quatitification with morphometry in neuroendocrine neoplasms and Ki-67 evaluation, BP.IC; 20/01758-8 - Study of cellular, subcellular (especially mitochondria) and matrix components of bronchioles, alveoli and diaphragms by electron microscopy in pre-clinical models of gene and drug therapy and ventilatory strategies in asthma and COPD, BP.TT; 19/12151-0 - Evaluation of the protein expression of DLL-3 and ASCL-1 as a new perspective in biomarkers for the early diagnosis of small cell lung carcinomas, BP.PD

Abstract

The prevalence and social cost of respiratory diseases such as lung cancer, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease, asthma, silicosis, and pulmonary arterial hypertension are high and some of them have few therapeutic alternatives. The therapy of most of these diseases is based on symptomatic control and not on effective cure. The present proposal has as main objective the understanding of the activation and regulation pathways of the cellular responses to insults and also the development of the underlying mechanisms in the repair and remodeling of the lesions. There is a consensus that the elucidation of the pathways and factors involved in these responses will increase the ability to identify and develop more effective treatments for disease control as proposed in this project. The project will have the participation of researchers linked to 7 different institutions: (1) University of São Paulo: Pathology Department of FMUSP-SP, (2) University of São Paulo: Rheumatology Department of FMUSP-SP, São Paulo: Department of Pathology of FMUSP-RP, (4) Federal University of Rio de Janeiro: Carlos Chagas Filho Institute of Biophysics, (5) Universidade Estadual Paulista: Department of Genetics of IBB / UNESP, (6) Hospital AC Camargo Cancer Center and (7) Hospital de Cancer de Barretos. It is worth emphasizing the active participation of emerging researchers included in the group that maintains a work association and co-authorship of different degrees and extensions, as a result of post-doctoral or postdoctoral orientation histories. Post-doctoral students, graduate students and scientific initiation, as well as laboratory technicians, will participate in different subprojects generated from this proposal already in progress. This project will also count on the collaboration of professors and researchers outside Brazil: Dr. Ignacio Wistuba and Dr. Edwin Roger Parra - The University of Texas, M.D. Anderson Cancer Center, Department of Translational Molecular Pathology, USA. Postdoctoral student (Brazil) - The University of Texas, M.D. Anderson Cancer Center, Department of Translational Molecular Pathology, USA; Prof. Dr. Sem H. Phan, University of Michigan, Ann Arbor-MI, USA. The researchers associated with this proposal propose, with knowledge and experience - in several cases jointly acquired - to advance in the investigation of biomarkers that may contribute to the development of new therapeutic strategies in respiratory diseases. (AU)

Scientific publications

(16)

(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)

BALANCIN, MARCELO LUIZ; TEODORO, WALCY ROSOLIA; FARHAT, CECILIA; DE MIRANDA, TOMAS JURANDIR; ASSATO, ALINE KAWASSAKI; DE SOUZA SILVA, NEILA APARECIDA; VELOSA, ANA PAULA; FALZONI, ROBERTO; AB'SABER, ALEXANDRE MUXFELDT; RODEN, ANJA C.; et al. An integrative histopathologic clustering model based on immuno-matrix elements to predict the risk of death in malignant mesothelioma. CANCER MEDICINE, v. 9, n. 13, MAY 2020. (18/20403-6)

BALANCIN, MARCELO LUIZ; TEODORO, WALCY ROSOLIA; BALDAVIRA, CAMILA MACHADO; PRIETO, TABATHA GUTIERREZ; FARHAT, CECILIA; VELOSA, ANA PAULA; SOUZA, PAOLA DA COSTA; YAEGASHI, LYGIA BERTALHA; AB'SABER, ALEXANDRE MUXFELDT; TAKAGAKI, TERESA YAE; et al. Different histological patterns of type-V collagen levels confer a matrices-privileged tissue microenvironment for invasion in malignant tumors with prognostic value. PATHOLOGY RESEARCH AND PRACTICE, v. 216, n. 12, DEC 2020. (18/20403-6)

PRIETO, TABATHA GUTIERREZ; BALDAVIRA, CAMILA MACHADO; MACHADO-RUGOLO, JULIANA; FARHAT, CECILIA; RIBEIRO OLIVIERI, ELOISA HELENA; DE SA, VANESSA KAREN; ABILIO DA SILVA, EDUARDO CAETANO; BALANCIN, MARCELO LUIZ; AB SABER, ALEXANDRE MUXFELDT; TAKAGAKI, TERESA YAE; et al. Pulmonary Neuroendocrine Neoplasms Overexpressing Epithelial-Mesenchymal Transition Mechanical Barriers Genes Lack Immune-Suppressive Response and Present an Increased Risk of Metastasis. FRONTIERS IN ONCOLOGY, v. 11, AUG 30 2021. (18/20403-6, 19/12151-0)

PEREIRA VELOSA, ANA PAULA; BRITO, LAIS; DE JESUS QUEIROZ, ZELITA APARECIDA; CARRASCO, SOLANGE; DE MIRANDA, JURANDIR TOMAZ; FARHAT, CECILIA; GOLDENSTEIN-SCHAINBERG, CLAUDIA; PARRA, EDWIN ROGER; OLIVEIRA DE ANDRADE, DANIELI CASTRO; SILVA, PEDRO LEME; et al. Identification of Autoimmunity to Peptides of Collagen V alpha 1 Chain as Newly Biomarkers of Early Stage of Systemic Sclerosis. FRONTIERS IN IMMUNOLOGY, v. 11, FEB 12 2021. (16/05617-4, 17/11865-3, 18/20403-6)

MARANGONI, ROBERTA GONCALVES; KORMAN, BENJAMIN D.; PARRA, EDWIN R.; VELOSA, ANA PAULA P.; BARBEIRO, V, HERMES; MARTINS, VANESSA; DOS SANTOS, ANGELA B. G.; SORIANO, FRANCISCO; TEODORO, WALCY R.; SILVA, PEDRO LEME; et al. Pathological pulmonary vascular remodeling is induced by type V collagen in a model of scleroderma. PATHOLOGY RESEARCH AND PRACTICE, v. 220, APR 2021. (18/20403-6)

BRINDO DA CRUZ, ISABELE CAMARGO; VELOSA, ANA PAULA PEREIRA; CARRASCO, SOLANGE; DOS SANTOS FILHO, ANTONIO; TOMAZ DE MIRANDA, JURANDIR; POMPEU, EDUARDO; FERNANDES, TIAGO LAZZARETTI; BUENO, DANIELA FRANCO; FANELLI, CAMILA; GOLDENSTEIN-SCHAINBERG, CLAUDIA; et al. Post-Adipose-Derived Stem Cells (ADSC) Stimulated by Collagen Type V (Col V) Mitigate the Progression of Osteoarthritic Rabbit Articular Cartilage. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, MAR 22 2021. (18/20403-6, 14/11419-5)

FABRO, ALEXANDRE TODOROVIC; MACHADO-RUGOLO, JULIANA; BALDAVIRA, CAMILA MACHADO; PRIETO, TABATHA GUTIERREZ; FARHAT, CECILIA; ROTEA MANGONE, FLAVIA REGINA; BATAH, SABRINA SETEMBRE; CRUVINEL, HELOISA RESENDE; ALDA, MAIARA ALMEIDA; MONTEIRO, JHONATAS SIRINO; et al. Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension. FRONTIERS IN PHARMACOLOGY, v. 12, MAY 28 2021. (15/06387-0, 18/20403-6, 15/06708-0)

BALDAVIRA, CAMILA M.; MACHADO-RUGOLO, JULIANA; PRIETO, TABATHA G.; BASTOS, DANIEL R.; BALANCIN, MARCELO; AB'SABER, ALEXANDRE M.; YAEGASHI, LYGIA B.; SOUZA, PAOLA C.; FARHAT, CECILIA; TAKAGAKI, TERESA Y.; et al. The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma. JOURNAL OF THORACIC DISEASE, v. 13, n. 2, FEB 2021. (18/20403-6)

MARTINS, VANESSA; DA SILVA, ADRIANA LOPES; TEODORO, WALCY ROSOLIA; PEREIRA VELOSA, ANA PAULA; BALANCIN, MARCELO LUIZ; CRUZ, FERNANDA FERREIRA; SILVA, PEDRO LEME; MACEDO ROCCO, PATRICIA RIEKEN; CAPELOZZI, VERA LUIZA. In situ evidence of collagen V and signaling pathway of found inflammatory zone 1 (FIZZ1) is associated with silicotic granuloma in lung mice. PATHOLOGY RESEARCH AND PRACTICE, v. 216, n. 9, SEP 2020. (16/21429-3, 18/20403-6)

C.M. BALDAVIRA; L.F. GOMES; L.T. DE LA CRUZ; D.A. MARIA; V.L. CAPELOZZI. In vivo evidence of angiogenesis inhibition by β2-glycoprotein I subfractions in the chorioallantoic membrane of chicken embryos. Brazilian Journal of Medical and Biological Research, v. 54, n. 3, 2021-01-15. (18/20403-6)

TEODORO, WALCY ROSOLIA; DE JESUS QUEIROZ, ZELITA APARECIDA; DOS SANTOS, LAIS ARAUJO; CATANOZI, SERGIO; DOS SANTOS FILHO, ANTONIO; BUENO, CLEONICE; VENDRAMINI, MARGARETE B. G.; FERNEZLIAN, SANDRA DE MORAIS; EHER, ESMERALDA M.; SAMPAIO-BARROS, PERCIVAL D.; et al. Proposition of a novel animal model of systemic sclerosis induced by type V collagen in C57BL/6 mice that reproduces fibrosis, vasculopathy and autoimmunity. ARTHRITIS RESEARCH & THERAPY, v. 21, n. 1, DEC 1 2019. (18/24210-8, 18/20403-6, 16/05617-4, 18/00415-0)

J. CHINOCA; D.S. ANDRADE; A. MENDES; P. DE MARCHI; T.G. PRIETO; C.M. BALDAVIRA; C. FARHAT; J.R.M. MARTINS; H.B. NADER; D.M. CARRARO; et al. Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum. Brazilian Journal of Medical and Biological Research, v. 55, 2022-01-25. (18/20403-6, 15/26642-4)

MACHADO-RUGOLO, JULIANA; PRIETO, TABATHA GUTIERREZ; FABRO, ALEXANDRE TODOROVIC; PARRA CUENTAS, EDWIN ROGER; SA, VANESSA KAREN; BALDAVIRA, CAMILA MACHADO; RAINHO, CLAUDIA APARECIDA; CASTELLI, ERICK C.; FARHAT, CECILIA; TAKAGAKI, TERESA YAE; et al. Relevance of PD-L1 Non-Coding Polymorphisms on the Prognosis of a Genetically Admixed NSCLC Cohort. PHARMACOGENOMICS & PERSONALIZED MEDICINE, v. 14, p. 239-252, 2021. (18/20403-6, 13/14277-4)

PRIETO, TABATHA GUTIERREZ; MACHADO-RUGOLO, JULIANA; BALDAVIRA, CAMILA MACHADO; VELOSA, ANA PAULA PEREIRA; TEODORO, WALCY ROSOLIA; AB SABE, ALEXANDRE MUXFELDT; CAPELOZZI, VERA LUIZA. The Fibrosis-Targeted Collagen/Integrins Gene Profile Predicts Risk of Metastasis in Pulmonary Neuroendocrine Neoplasms. FRONTIERS IN ONCOLOGY, v. 11, AUG 11 2021. (18/20403-6, 19/12151-0)

BALDAVIRA, C. M.; GOMES, L. F.; DE LA CRUZ, L. T.; MARIA, D. A.; CAPELOZZI, V. L.. In vivo evidence of angiogenesis inhibition by beta(2)-glycoprotein I subfractions in the chorioallantoic membrane of chicken embryos. Brazilian Journal of Medical and Biological Research, v. 54, n. 3, 2021. (18/20403-6)

FELIX, RENATO GONCALVES; CARVALHO BOVOLATO, ANA LIVIA; COTRIM, ONDINA SILVIA; LEAO, PATRICIA DOS SANTOS; BATAH, SABRINA SETEMBRE; GOLIM, MARJORIE DE ASSIS; VELOSA, ANA PAULA; TEODORO, WALCY; MARTINS, VANESSA; CRUZ, FERNANDA FERREIRA; et al. Adipose-derived stem cells and adipose-derived stem cell-conditioned medium modulate in situ imbalance between collagen I-and collagen V-mediated IL-17 immune response recovering bleomycin pulmonary fibrosis. HISTOLOGY AND HISTOPATHOLOGY, v. 35, n. 3, p. 289-301, MAR 2020. (11/09181-2, 18/20403-6, 13/14277-4, 12/03543-2, 12/07040-5)