Establishment of a center of genetic and molecular research for clinical challenges

• Grant number: 14/27198-8
• Support type: Research Projects - Thematic Grants
• Duration: June 01, 2016 - February 28, 2021
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal researcher: João Bosco Pesquero
• Grantee: João Bosco Pesquero
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Principal researchers: Dirceu Solé ; Dirceu Solé ; Dirceu Solé ; Maria Cristina de Oliveira Izar ; Maria Cristina de Oliveira Izar ; Maria Cristina de Oliveira Izar ; Paulo Cesar Koch Nogueira ; Paulo Cesar Koch Nogueira ; Paulo Cesar Koch Nogueira
• Assoc. researchers: Ana Beatriz Alvarez Perez ; Beatriz Tavares Costa Carvalho ; Eli Mansur ; Francisco Antonio Helfenstein Fonseca ; Houtan Noushmehr ; Luis Felipe Chiaverini Ensina ; Maria Cristina de Oliveira Izar ; Maria Isabel de Moraes Pinto ; Roseli Oselka Saccardo Sarni ; Sonia Hix ; Vânia D'Almeida
• Associated grant(s): 19/06543-2 - Angioedema and bradykinin receptors in the endothelium, AP.R SPRINT
• Associated scholarship(s): 19/12261-0 - Functional characterization of new variants presents in the GLA gene of patients with suspicion of Fabry disease, BP.MS; 19/13637-3 - Pharmacological analyzes in iPSC-derived cardiomyocytes of patients with Fabry Disease, BP.PD; 17/24857-9 - APOB gene study in patients with Familial Hypercholesterolemia, BP.IC; + associated scholarships 17/00719-6 - The study of genetic and molecular profile of kallikrein-kinin system in familial hypercholesterolemia patients, BP.MS; 16/10319-2 - The study of genetic and molecular profile of renin-angiotensin-aldosterone in familial hypercholesterolemia patients, BP.PD; 15/25494-1 - Development of a gene therapy model for hereditary angioedema based on SERPING1 gene edition by CRISPR-Cas9 system, BP.PD; 14/20965-3 - In silico study of genetic mutations causing hereditary angioedema, BP.PD - associated scholarships

Abstract

New models of organization and health practices in Brazil are efforts to improve services and an approach based not only on the disease, but in the health-disease process aiming prevention and quality of life. The emphasis on healthy habits among the population is a milestone, increased motivation to adopt healthy habits, greater interest in having a healthy body, further knowledge on genetic determinants and the appreciation of the benefits of physical activity and exercise to the health and quality of life. The promotion of health has to find proposals to meet emerging issues in our society in a way that has an overview of "microdeterminants" and "macrodeterminants" of the health-disease process. To create new opportunities for health intervention is necessary in the ongoing effort to study the physiology of the human body along with the pursuit of thorough knowledge of the genotype and phenotype interaction. A major goal of human genetics is to understand how changes in the DNA of individuals provide the development of disease, and the biggest challenge is the search for correlations between genotype and phenotype. The approach for molecular genetic studies of complex phenotypes has evolved considerably during the past few years, the next-generation sequencing (NGS) has enabled great advances and contributed greatly to the evolution of medicine. The research in our group for several years has been concentrated on systems like kallikrein kinins and renin angiotensin, primarily using transgenic animals, enzyme kinetics and gene expression in general. All this history has brought us extensive experience in molecular biology. Along the years we have increased our knowledge on genetic diseases and also in the genotype phenotype correlation in physical activity and sports. The fundamental connection between all these projects is the need for deepening genetic studies to bring further progress in the area, since they are all "clinical challenges", due to their complexity or due to the mosaic of events that hinder the genotype and phenotype correlation. These studies are crucial to advances in screening and diagnosis, development of new therapeutic and preventive approaches, supporting quality of life, as well as in the quest for a healthy body. Thus we aimed to establish a center of genetic research, which will be a very important OMIC tool to assist in the conduct of "clinical challenges" as well as for physical and sport performance, representing a new benchmark for genetic and molecular studies in Brazil. (AU)

Scientific publications

(20)

(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)

WATANABE, ANDREIA; GUARAGNA, MARA SANCHES; SANTORO BELANGERO, VERA MARIA; SERAFIM CASIMIRO, FERNANDA MARIA; PESQUERO, JOAO BOSCO; FELTRAN, LUCIANA DE SANTIS; PEREIRA PALMA, LILIAN MONTEIRO; VARELA, PATRICIA; MIRANDA DE MENEZES NEVES, PRECIL DIEGO; LERARIO, ANTONIO MARCONDES; DE SOUZA, MARCELA LOPES; DE MELLO, MARICILDA PALANDI; GERVASIO DE BRITO LUTAIF, ANNA CRISTINA; FERRARI, CASSIO RODRIGUES; SAMPSON, MATTHEW GORDON; ONUCHIC, LUIZ FERNANDO; KOCH NOGUEIRA, PAULO CESAR. APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses. Pediatric Nephrology, v. 36, n. 8, SI FEB 2021. Web of Science Citations: 0.

CESPEDES, ISABEL CRISTINA; OTA, VANESSA KIYOMI; MAZZOTTI, DIEGO ROBLES; WSCIEKLICA, TATIANA; CONTE, RAFAEL; GALDUROZ, JOSE CARLOS FERNANDES; VARELA, PATRICIA; PESQUERO, JOAO BOSCO; SOUZA-FORMIGONI, MARIA LUCIA OLIVEIRA. Association between polymorphism in gene related to the dopamine circuit and motivations for drinking in patients with alcohol use disorder. PSYCHIATRY RESEARCH, v. 295, JAN 2021. Web of Science Citations: 0.

GOMES, CAIO P.; FERNANDES, DANILO E.; CASIMIRO, FERNANDA; MATA, GUSTAVO F.; PASSOS, MICHELLE T.; VARELA, PATRICIA; MASTROIANNI-KIRSZTAJN, GIANNA; PESQUERO, JOAO BOSCO. Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, DEC 8 2020. Web of Science Citations: 1.

VARELA, PATRICIA; CARVALHO, GERSON; MARTIN, RENAN PAULO; PESQUERO, JOAO BOSCO. Fabry disease: GLA deletion alters a canonical splice site in a family with neuropsychiatric manifestations. METABOLIC BRAIN DISEASE, v. 36, n. 2 NOV 2020. Web of Science Citations: 0.

RIGUETTI, MICHELLE T. P.; VARELA, PATRICIA; FERNANDES, DANILO E.; POLITO, M. GORETTI; CASIMIRO, FERNANDA M.; PESQUERO, JOAO B.; MASTROIANNI-KIRSZTAJN, GIANNA. Familial Focal Segmental Glomerulosclerosis With Late-Onset Presentation and R229Q/R291W Podocin Mutations. FRONTIERS IN GENETICS, v. 11, SEP 16 2020. Web of Science Citations: 0.

GOMES, CAIO PEREZ; MARINS, MARYANA MARA; MOTTA, FABIANA LOUISE; KYOSEN, SANDRA OBIKAWA; CURIATI, MARCO ANTONIO; D'ALMEIDA, VANIA; MARTINS, ANA MARIA; PESQUERO, JOAO BOSCO. A New Mutation in IDS Gene Causing Hunter Syndrome: A Case Report. FRONTIERS IN GENETICS, v. 10, MAR 18 2020. Web of Science Citations: 0.

FELTRAN, LUCIANA S.; WATANABE, ANDREIA; GUARAGNA, MARA S.; MACHADO, IVAN C.; CASIMIRO, FERNANDA M. S.; NEVES, PRECIL D. M. M.; PALMA, LILIAN M.; VARELA, PATRICIA; VAISBICH, MARIA H.; MARIE, SUELY K. N.; FACINCANI, INALDA; PESQUERO, JOAO B.; BELANGERO, VERA M. S.; SAMPSON, MATTHEW G.; KOCH NOGUEIRA, PAULO C.; ONUCHIC, LUIZ F. Brazilian Network of Pediatric Nephrotic Syndrome (REBRASNI). KIDNEY INTERNATIONAL REPORTS, v. 5, n. 3, p. 358-362, MAR 2020. Web of Science Citations: 0.

VARELA, PATRICIA; MASTROIANNI KIRSZTAJN, GIANNA; FERRER, HENRIQUE; ARANDA, CAROLINA; WALLBACH, KRISSIA; FERREIRA DA MATA, GUSTAVO; MOURA, LUIZ A.; MOREIRA, SILVIA R.; MENDES, CARMEN; CURIATI, MARCO A.; MARTINS, ANA MARIA; BOSCO PESQUERO, JOAO. Functional Characterization and Pharmacological Evaluation of a Novel GLA Missense Mutation Found in a Severely Affected Fabry Disease Family. NEPHRON, v. 144, n. 3, p. 147-155, MAR 2020. Web of Science Citations: 1.

VARELA, PATRICIA; MASTROIANNI KIRSZTAJN, GIANNA; MOTTA, FABIANA L.; MARTIN, RENAN P.; TURACA, LAURO T.; FERRER, HENRIQUE L. F.; GOMES, CAIO P.; NICOLICHT, PRISCILA; MARA MARINS, MARYANA; PESSOA, JULIANA G.; BRAGA, MARION C.; D'ALMEIDA, VANIA; MARTINS, ANA MARIA; PESQUERO, JOAO B. Correlation between GLA variants and alpha-Galactosidase A profile in dried blood spot: an observational study in Brazilian patients. ORPHANET JOURNAL OF RARE DISEASES, v. 15, n. 1 JAN 29 2020. Web of Science Citations: 0.

BOTTURA, RICARDO MULLER; OLIVEIRA LIMA, GISCARD HUMBERTO; HIPOLIDE, DEBORA CRISTINA; PESQUERO, JOAO BOSCO. Association between ACTN3 and acute mountain sickness. GENES AND ENVIRONMENT, v. 41, n. 1 DEC 10 2019. Web of Science Citations: 1.

GUIMARAES, PAOLA BIANCHI; DA SILVA, RAFAEL FILIPPELLI; HOFF, CAROLINA CALDAS; FERNANDES, LILIAM; NAKAIE, CLOVIS RYUICHI; CHAGAS, JAIR RIBEIRO; CARMONA, ADRIANA KARAOGLANOVIC; BADER, MICHAEL; PESQUERO, JOAO BOSCO. Interactions between carboxypeptidase M and kinin B1 receptor in endothelial cells. Inflammation Research, v. 68, n. 10, p. 845-855, OCT 2019. Web of Science Citations: 0.

VARELA, PATRICIA; CALDAS, MYRTES MARTINS; PESQUERO, JOAO BOSCO. Novel GLA Mutation Promotes Intron Inclusion Leading to Fabry Disease. FRONTIERS IN GENETICS, v. 10, SEP 27 2019. Web of Science Citations: 0.

DE OLIVEIRA, VIVIAN CRISTINA; DE LACERDA, MARCELO PITOMBEIRA; MUNIZ MORAES, BARBARA BOMFIM; GOMES, CAIO PEREZ; MARICATO, JULIANA TERZI; SOUZA, OLIVIA FONSECA; SCHENKMAN, SERGIO; PESQUERO, JOAO BOSCO; MORETTI, NILMAR SILVIO; RODRIGUES, CELSO ARRAIS; POP, ANA FLAVIA. Deregulation of Ikaros expression in B-1 cells: New insights in the malignant transformation to chronic lymphocytic leukemia. Journal of Leukocyte Biology, v. 106, n. 3, SI, p. 581-594, SEP 2019. Web of Science Citations: 0.

SALES, VICENCIA M.; GONCALVES-ZILLO, THAIS; CASTOLDI, ANGELA; BURGOS, MARINA; BRANQUINHO, JESSICA; BATISTA, CAROLINA; OLIVEIRA, VALERIA; SILVA, ELTON; CASTRO, CHARLLES H. M.; CAMARA, NIELS; MORI, MARCELO A.; PESQUERO, JOAO BOSCO. Kinin B-1 Receptor Acts in Adipose Tissue to Control Fat Distribution in a Cell-Nonautonomous Manner. Diabetes, v. 68, n. 8, p. 1614-1623, AUG 2019. Web of Science Citations: 1.

RENNO SIERRA, ANA PAULA; OLIVEIRA, RODRIGO ASSUNCAO; SILVA, ELTON DIAS; OLIVEIRA LIMA, GISCARD HUMBERTO; BENETTIL, MARINO PEREIRA; PEDANTI KISS, MARIA AUGUSTA; SIERRA, CARLOS ANIBAL; GHORAYEB, NABIL; SETO, JANE T.; PESQUERO, JOAO BOSCO; CURY-BOAVENTURA, MARIA FERNANDA. Association Between Hematological Parameters and Iron Metabolism Response After Marathon Race and ACTN3 Genotype. FRONTIERS IN PHYSIOLOGY, v. 10, JUN 11 2019. Web of Science Citations: 0.

VERONEZ, CAMILA LOPES; CAMPOS, REGIS ALBUQUERQUE; CONSTANTINO-SILVA, ROSEMEIRE NAVICKAS; NICOLICHT, PRISCILA; PESQUERO, JOAO BOSCO; GRUMACH, ANETE SEVCIOVIC. Hereditary Angioedema-Associated Acute Pancreatitis in C1-Inhibitor Deficient and Normal C1-Inhibitor Patients: Case Reports and Literature Review. FRONTIERS IN MEDICINE, v. 6, APR 17 2019. Web of Science Citations: 0.

VERONEZ, CAMILA LOPES; AABOM, ANNE; MARTIN, RENAN PAULO; FILIPPELLI-SILVA, RAFAEL; GONCALVES, ROZANA FATIMA; NICOLICHT, PRISCILA; MENDES, AGATHA RIBEIRO; DA SILVA, JANE; GUILARTE, MAR; GRUMACH, ANETE SEVCIOVIC; MANSOUR, ELI; BYGUM, ANETTE; PESQUERO, JOAO BOSCO. Genetic Variation of Kallikrein-Kinin System and Related Genes in Patients With Hereditary Angioedema. FRONTIERS IN MEDICINE, v. 6, FEB 21 2019. Web of Science Citations: 0.

NICOLICHT, PRISCILA; FARIA, DOUGLAS O. S.; MARTINS-SILVA, LEONARDO; MAIA, LUANA S. M.; MORENO, ADRIANA S.; KARLA ARRUDA, L.; MOTTA, ANTONIO A.; GRUMACH, ANETE S.; PESQUERO, JOAO B. Gene mapping strategy for Alu elements rearrangements: Detection of new large deletions in the SERPING1 gene causing hereditary angioedema in Brazilian families. Gene, v. 685, p. 179-185, FEB 15 2019. Web of Science Citations: 3.

VERONEZ, CAMILA LOPES; MORENO, ADRIANA S.; CONSTANTINO-SILVA, ROSEMEIRE NAVICKAS; MAIA, LUANA S. M.; FERRIANI, MARIANA P. L.; CASTRO, FABIO F. M.; VALLE, SOLANGE RODRIGUES; NAKAMURA, VICTOR KOJI; CAGINI, NATHALIA; GONCALVES, ROZANA FATIMA; MANSOUR, ELI; SERPA, FARADIBA SARQUIS; COELHO DIAS, GABRIELA ANDRADE; PICCIRILLO, MIGUEL ALBERTO; TOLEDO, ELIANA; BERNARDES, MARLI DE SOUZA; CICHON, SVEN; STIEBER, CHRISTIANE; ARRUDA, L. KARLA; PESQUERO, JOAO BOSCO; GRUMACH, ANETE SEVCIOVIC. Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, v. 6, n. 4, p. 1209+, JUL-AUG 2018. Web of Science Citations: 10.

FELTRAN, LUCIANA S.; VARELA, PATRICIA; SILVA, ELTON DIAS; VERONEZ, CAMILA LOPES; FRANCO, MARIA CARMO; PACHECO FILHO, ALVARO; CAMARGO, MARIA FERNANDA; KOCH NOGUEIRA, PAULO CESAR; PESQUERO, JOAO BOSCO. Targeted Next-Generation Sequencing in Brazilian Children With Nephrotic Syndrome Submitted to Renal Transplant. TRANSPLANTATION, v. 101, n. 12, p. 2905-2912, DEC 2017. Web of Science Citations: 5.