LUCAS AUGUSTO MOYSES FRANCO
Projetos de Pesquisa
Unidades Organizacionais
LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature(2022) SABINO, Ester Cerdeira; FRANCO, Lucas Augusto Moyses; VENTURINI, Gabriela; RODRIGUES, Mariliza Velho; MARQUES, Emanuelle; SILVA, Lea Campos de Oliveira-da; MARTINS, Larissa Natany Almeida; FERREIRA, Ariela Mota; ALMEIDA, Paulo Emilio Clementino; SILVA, Felipe Dias Da; LEITE, Samara Fernandes; NUNES, Maria do Carmo Pereira; HAIKAL, Desiree Sant'Ana; OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci Silva; SEIDMAN, Jonathan G.; SEIDMAN, Christine E.; CASAS, Juan P.; RIBEIRO, Antonio Luiz Pinho; KRIEGER, Jose E.; PEREIRA, Alexandre C.Background Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. Methodology/Principal findings We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10(-9)) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302-5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. Conclusions/Significance We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.
- Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil(2021) FARIA, Nuno R.; MELLAN, Thomas A.; WHITTAKER, Charles; CLARO, Ingra M.; CANDIDO, Darlan da S.; MISHRA, Swapnil; CRISPIM, Myuki A. E.; SALES, Flavia C.; HAWRYLUK, Iwona; MCCRONE, John T.; HULSWIT, Ruben J. G.; FRANCO, Lucas A. M.; RAMUNDO, Mariana S.; JESUS, Jaqueline G. de; ANDRADE, Pamela S.; COLETTI, Thais M.; FERREIRA, Giulia M.; SILVA, Camila A. M.; MANULI, Erika R.; PEREIRA, Rafael H. M.; PEIXOTO, Pedro S.; KRAEMER, Moritz U.; GABURO JR., Nelson; CAMILO, Cecilia da C.; HOELTGEBAUM, Henrique; SOUZA, William M.; ROCHA, Esmenia C.; SOUZA, Leandro M. de; PINHO, Mariana C. de; ARAUJO, Leonardo J. T.; V, Frederico S. Malta; LIMA, Aline B. de; SILVA, Joice do P.; ZAULI, Danielle A. G.; FERREIRA, Alessandro C. de S.; SCHNEKENBERG, Ricardo P.; LAYDON, Daniel J.; WALKER, Patrick G. T.; SCHLUETER, Hannah M.; SANTOS, Ana L. P. dos; VIDAL, Maria S.; CARO, Valentina S. Del; FILHO, Rosinaldo M. F.; SANTOS, Helem M. dos; AGUIAR, Renato S.; PROENCA-MODENA, Jose L. P.; NELSON, Bruce; HAY, James A.; MONOD, Melodie; MISCOURIDOU, Xenia; COUPLAND, Helen; SONABEND, Raphael; VOLLMER, Michaela; GANDY, Axel; PRETE JR., Carlos A.; NASCIMENTO, Vitor H.; SUCHARD, Marc A.; BOWDEN, Thomas A.; POND, Sergei L. K.; WU, Chieh-Hsi; RATMANN, Oliver; FERGUSON, Neil M.; DYE, Christopher; LOMAN, Nick J.; LEMEY, Philippe; RAMBAUT, Andrew; FRAIJI, Nelson A.; CARVALHO, Maria do P. S. S.; PYBUS, Oliver G.; FLAXMAN, Seth; BHATT, Samir; SABINO, Ester C.Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.
- Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole(2021) FRANCO, Lucas A. M.; MOREIRA, Carlos H. V.; BUSS, Lewis F.; OLIVEIRA, Lea C.; MARTINS, Roberta C. R.; MANULI, Erika R.; LINDOSO, Jose A. L.; BUSCH, Michael P.; PEREIRA, Alexandre C.; SABINO, Ester C.Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. Methods: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. Results: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 x 10(-8)). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. Conclusions: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment.
- Salivary Microbial Dysbiosis Is Associated With Peri-Implantitis: A Case-Control Study in a Brazilian Population(2022) PALLOS, Debora; SOUSA, Vanessa; FERES, Magda; RETAMAL-VALDES, Belen; CHEN, Tsute; CURTIS, Mike; BOAVENTURA, Richardson Mondego; TANAKA, Marcia Hiromi; SALOMAO, Gustavo Vargas da Silva; ZANELLA, Louise; TOZETTO-MENDOZA, Tania Regina; SCHWAB, Gabriela; FRANCO, Lucas Augusto Moyses; SABINO, Ester Cerdeira; BRAZ-SILVA, Paulo Henrique; SHIBLI, Jamil AwadBackground and ObjectivesThe aim of this study was to examine the salivary microbiome in healthy peri-implant sites and those with peri-implantitis. MethodsSaliva samples were collected from 21 participants with healthy peri-implant sites and 21 participants with peri-implantitis. The V4 hypervariable region of the 16S rRNA gene was sequenced using the Ion Torrent PGM System (Ion 318 (TM) Chip v2 400). The NGS analysis and composition of the salivary microbiome were determined by taxonomy assignment. Downstream bioinformatic analyses were performed in QIIME (v 1.9.1). ResultsClinical differences according to peri-implant condition status were found. Alpha diversity metrics revealed that the bacterial communities of participants with healthy peri-implant sites tended to have a richer microbial composition than individuals with peri-implantitis. In terms of beta diversity, bleeding on probing (BoP) may influence the microbial diversity. However, no clear partitioning was noted between the salivary microbiome of volunteers with healthy peri-implant sites or volunteers with peri-implantitis. The highest relative abundance of Stenotrophomonas, Enterococcus and Leuconostoc genus, and Faecalibacterium prausnitzii, Haemophilus parainfluenzae, Prevotella copri, Bacteroides vulgatus, and Bacteroides stercoris bacterial species was found in participants with peri-implantitis when compared with those with healthy peri-implant sites. ConclusionDifferences in salivary microbiome composition were observed between patients with healthy peri-implant sites and those with peri-implantitis. BoP could affect the diversity (beta diversity) of the salivary microbiome.