LUCIANI RENATA SILVEIRA DE CARVALHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject p.Gln207Arg GH1 allelic variant associated to GH deficiency and specific intronic region may be a modulator of GH secretion(2023) SASSON, Tessa; DAUBER, Andrew; JORGE, Alexander; PANDEY, Amit; ARNHOLD, Ivo; CARVALHO, Luciani- A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity(2023) BASTOS, Thais Sibioni Berti; PAULA, Andre Guilherme Portela de; LUZ, Rebeca Bosso dos Santos; GARNIQUE, Anali M. B.; BELO, Marco A. A.; ETO, Silas Fernandes; FERNANDES, Dayanne Carla; FERRARIS, Fausto Klabund; PONTES, Leticia Gomes de; FRANCA, Tabata Takahashi; BARCELLOS, Leonardo Jose Gil; VERAS, Flavio P.; BERMEJO, Pamela; GUIDELLI, Giovanna; MANEIRA, Carla; MELLO, Fellipe da Silveira Bezerra de; TEIXEIRA, Gleidson; PEREIRA, Goncalo Amarante Guimaraes; FERNANDES, Bianca H. Ventura; SANCHES, Paulo R. S.; BRAZ, Helyson Lucas Bezerra; JORGE, Roberta Jeane Bezerra; MALAFAIA, Guilherme; CILLI, Eduardo M.; OLIVIER, Danilo da Silva; AMARAL, Marcos Serrou do; MEDEIROS, Renata J.; CONDINO-NETO, Antonio; CARVALHO, Luciani R.; MACHADO-SANTELLI, Glaucia M.; CHARLIE-SILVA, Ives; GALINDO-VILLEGAS, Jorge; BRAGA, Tarcio TeodoroDespite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-alpha and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.
- Homozygous CDH2 variant may be associated with hypopituitarism without neurological disorders(2023) FERREIRA, Nathalia G. B. P.; MADEIRA, Joao L. O.; GERGICS, Peter; KERTSZ, Renata; MARQUES, Juliana M.; TRIGUEIRO, Nicholas S. S.; BENEDETTI, Anna Flavia Figueredo; V, Bruna Azevedo; V, Bianca H. Fernandes; BISSEGATTO, Debora D.; BISCOTTO, Isabela P.; FANG, Qing; MA, Qianyi; OZEL, Asye B.; LI, Jun; CAMPER, Sally A.; JORGE, Alexander A. L.; MENDONCA, Berenice B.; ARNHOLD, Ivo J. P.; CARVALHO, Luciani R.Context: Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition. Objectives: The aim of this study is to conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a no vel CDH2 variant. Design: Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD, and ABraOM), in silico prediction of pathogenicity, and gene expression in the pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing. Results: One female patient with deficiencies in growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wildtype CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected. Conclusion: A homozygous CDH2 allelic variant was found in one hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations.
conferenceObject GENERATING PITUITARY CELLS FROM INDUCED PLURIPOTENT STEM CELL (IPSC) OF PATIENTS WITH CHILD ONSET OF CONGENITAL HYPOPITUITARISM (CO-CH) HARBORING PROP1 PATHOGENIC ALLELIC VARIANTS(2023) MARQUES, J. Moreira; FATTAHI, F.; CARVALHO, L.- A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity (vol 13, 8060, 2023)(2023) BASTOS, Thais Sibioni Berti; PAULA, Andre Guilherme Portela de; LUZ, Rebeca Bosso dos Santos; GARNIQUE, Anali M. B.; BELO, Marco A. A.; ETO, Silas Fernandes; FERNANDES, Dayanne Carla; FERRARIS, Fausto Klabund; PONTES, Leticia Gomes de; FRANCA, Tabata Takahashi; BARCELLOS, Leonardo Jose Gil; VERAS, Flavio P. P.; BERMEJO, Pamela; GUIDELLI, Giovanna; MANEIRA, Carla; MELLO, Fellipe da Silveira Bezerra de; TEIXEIRA, Gleidson; PEREIRA, Goncalo Amarante Guimaraes; FERNANDES, Bianca H. Ventura; SANCHES, Paulo R. S.; BRAZ, Helyson Lucas Bezerra; JORGE, Roberta Jeane Bezerra; MALAFAIA, Guilherme; CILLI, Eduardo M. M.; OLIVIER, Danilo da Silva; AMARAL, Marcos Serrou do; MEDEIROS, Renata J. J.; CONDINO-NETO, Antonio; CARVALHO, Luciani R. R.; MACHADO-SANTELLI, Glaucia M. M.; CHARLIE-SILVA, Ives; GALINDO-VILLEGAS, Jorge; BRAGA, Tarcio Teodoro