Urine-Derived iPSC Neurospheres Uncover Proteomic Correlates of Clinical Severity in Dravet Syndrome Michele Martins, Guillaume Nugue, Andrey Aguiar, Leticia R. Q. Souza, Paulo V. Abrantes, Julia Rodrigues Trajano, Mariana Stelling, Magno Junqueira, Stevens Rehen, Marília Zaluar P. Guimarães Journal of Neurochemistry, 2026 Dravet syndrome (DS) is a rare and severe childhood‐onset developmental epileptic encephalopathy caused primarily by mutations in the sodium channel gene SCN1A. Animal models have undeniably advanced our understanding of DS, but they still do not fully capture its clinical heterogeneity, highlighting the need for complementary human in vitro systems. Here, we generated induced pluripotent stem cells (iPSCs) from urine epithelial cells of three DS patients carrying distinct SCN1A variants and differentiated them into neural stem cells (NSCs) and early‐stage neurospheres. Clinical severity was assessed using the DANCE checklist, and molecular phenotypes were characterized through isobaric quantitative proteomics. Comparative analyses identified differences in protein abundance across patient‐derived lines, with distinct molecular patterns associated with clinical severity measures. The patient‐derived lines exhibited variability in protein groups related to synaptic organization, mitochondrial processes, and RNA processing, reflecting interindividual molecular differences within the cohort. These findings establish patient‐derived neurospheres as a scalable human model for investigating molecular variability in DS. This approach provides a framework to explore disease heterogeneity and provides a foundation for future studies linking molecular profiles to clinical variability in DS. image
Lysergic acid diethylamide induces behavioral changes in Caenorhabditis elegans Isis M. Ornelas, Beatriz de S. Carrilho, Matheus Antonio V. de C. Ventura, Ivan Domith, Christiane M. de V. Silveira, Vanessa F. dos Santos, João M. Delou, Francisco Moll, Henrique Marcelo G. Pereira, Magno Junqueira, Hugo Aguilaniu, Stevens Rehen Neuroscience Letters, 2024
Cry1Ac toxin binding in the velvetbean caterpillar Anticarsia gemmatalis: study of midgut aminopeptidases N M. D. Lanzaro, I. Padilha, L. F. C. Ramos, A. P. G. Mendez, A. Menezes, Y. M. Silva, M. R. Martins, M. Junqueira, F. C. S. Nogueira, C. D. AnoBom, G. M. Dias, F. M. Gomes, D. M. P. Oliveira Frontiers in Physiology, 2024 The velvetbean caterpillar Anticarsia gemmatalis is one of the main soybean defoliators in Brazil. Currently, the main biopesticide used to control insect pests worldwide is the bacteria Bacillus thuringiensis (Bt), which produces entomopathogenic Crystal toxins (Cry) that act in the midgut of susceptible insects, leading them to death. The mode of action of Cry toxins in the midgut involves binding to specific receptors present on the brush border of epithelial cells such as aminopeptidase N (APN), alkaline phosphatase (ALP), cadherin, and others. Mutations in these receptors, among other factors, may be involved in the development of resistance; identification of functional Cry receptors in the midgut of A. gemmatalis is crucial to develop effective strategies to overcome this possible scenario. This study’s goal is to characterize APNs of A. gemmatalis and identify a receptor for Cry1Ac in the midgut. The interaction of Bt spores with the midgut epithelium was observed in situ by immunohistochemistry and total aminopeptidase activity was estimated in brush border membrane vesicle (BBMV) samples, presenting higher activity in challenged individuals than in control ones. Ten APN sequences were found in a A. gemmatalis’ transcriptome and subjected to different in silico analysis, such as phylogenetic tree, multiple sequence alignment and identification of signal peptide, activity domains and GPI-anchor signal. BBMV proteins from 5th instar larvae were submitted to a ligand blotting using activated Cry1Ac toxin and a commercial anti-Cry polyclonal antibody; corresponding bands of proteins that showed binding to Cry toxin were excised from the SDS-PAGE gel and subjected to mass spectrometry analysis, which resulted in the identification of seven of those APNs. Quantitative PCR was realized to compare expression levels between individuals subjected to sublethal infection with Bt spores and control ones, presenting up- and downregulations upon Bt infection. From these results, we can infer that aminopeptidases N in A. gemmatalis could be involved in the mode of action of Cry toxins in its larval stage.
Editorial: The application of OMICS technologies to interrogate host-virus interactions Fabio Gomes, Kendra Alfson, Magno Junqueira Frontiers in Cellular and Infection Microbiology, 2022 Viruses can infect all types of life forms, ranging from humans to bacteria. Highcontent data generated with omics technologies can be used to identify emergent properties of these systems, providing targets for further mechanistic investigations. Since the completion of the first genome sequencing projects, omics approaches have been used to study the dynamics and complexity of host-virus interactions. Starting with early microarray studies aiming to cover a fraction of the host genome and progressively moving into deep-sequencing projects, these studies shed light on the modulation of host gene expression profiles upon infection. In addition, changes in the protein level could be accessed via mass spectrometry-based proteomic methods (Luo and Muesing 2014), applied on a genome scale [reviewed in These investigations allowed direct protein quantification that partially validated previous transcriptomic findings and highlighted the complexity of the regulation of protein translation and post-translation modifications during virus infection More recently, network analysis has been progressively used to identify promising targets for therapeutic interventions and drug repurposing, and is now playing a role in vaccine development studies At the same time, reduced sequencing costs and evolving hardware capabilities now allow for massive projects involving multi-omics data integration
Interspecies Isobaric Labeling-Based Quantitative Proteomics Reveals Protein Changes in the Ovary of Aedes aegypti Coinfected With ZIKV and Wolbachia Luís Felipe Costa Ramos, Michele Martins, Jimmy Rodriguez Murillo, Gilberto Barbosa Domont, Danielle Maria Perpétua de Oliveira, Fábio César Sousa Nogueira, Rafael Maciel-de-Freitas, Magno Junqueira Frontiers in Cellular and Infection Microbiology, 2022 Zika is a vector-borne disease caused by an arbovirus (ZIKV) and overwhelmingly transmitted by Ae. aegypti. This disease is linked to adverse fetal outcomes, mostly microcephaly in newborns, and other clinical aspects such as acute febrile illness and neurologic complications, for example, Guillain-Barré syndrome. One of the most promising strategies to mitigate arbovirus transmission involves releasing Ae. aegypti mosquitoes carrying the maternally inherited endosymbiont bacteria Wolbachia pipientis. The presence of Wolbachia is associated with a reduced susceptibility to arboviruses and a fitness cost in mosquito life-history traits such as fecundity and fertility. However, the mechanisms by which Wolbachia influences metabolic pathways leading to differences in egg production remains poorly known. To investigate the impact of coinfections on the reproductive tract of the mosquito, we applied an isobaric labeling-based quantitative proteomic strategy to investigate the influence of Wolbachia wMel and ZIKV infection in Ae. aegypti ovaries. To the best of our knowledge, this is the most complete proteome of Ae. aegypti ovaries reported so far, with a total of 3913 proteins identified, were also able to quantify 1044 Wolbachia proteins in complex sample tissue of Ae. aegypti ovary. Furthermore, from a total of 480 mosquito proteins modulated in our study, we discuss proteins and pathways altered in Ae. aegypti during ZIKV infections, Wolbachia infections, coinfection Wolbachia/ZIKV, and compared with no infection, focusing on immune and reproductive aspects of Ae. aegypti. The modified aspects mainly were related to the immune priming enhancement by Wolbachia presence and the modulation of the Juvenile Hormone pathway caused by both microorganism’s infection.
Quantitative profiling of axonal guidance proteins during the differentiation of human neurospheres Livia Goto-Silva, Michele Martins, Jimmy Rodriguez Murillo, Leticia R.Q. Souza, Gabriela Vitória, Júlia T. Oliveira, Juliana M. Nascimento, Erick Correia Loiola, Fabio C.S. Nogueira, Gilberto B. Domont, Marília Zaluar P. Guimarães, Fernanda Tovar-Moll, Stevens Kastrup Rehen, Magno Junqueira Biochimica Et Biophysica Acta Proteins and Proteomics, 2021
Unraveling the processing and activation of snake venom metalloproteinases José A. Portes-Junior, Norma Yamanouye, Sylvia M. Carneiro, Paloma S. Knittel, Sávio S. Sant’Anna, Fabio C. S. Nogueira, Magno Junqueira, Geraldo S. Magalhães, Gilberto B. Domont, Ana M. Moura-da-Silva Journal of Proteome Research, 2014
Proteome analysis of plastids from developing seeds of Jatropha curcas L. Camila B. Pinheiro, Mohibullah Shah, Emanoella L. Soares, Fábio C. S. Nogueira, Paulo C. Carvalho, Magno Junqueira, Gabriel D. T. Araújo, Arlete A. Soares, Gilberto B. Domont, Francisco A. P. Campos Journal of Proteome Research, 2013
A genomic toolkit to investigate kinesin and myosin motor function in cells Zoltan Maliga, Magno Junqueira, Yusuke Toyoda, Andreas Ettinger, Felipe Mora-Bermúdez, Robin W. Klemm, Andrej Vasilj, Elaine Guhr, Itziar Ibarlucea-Benitez, Ina Poser, Ezio Bonifacio, Wieland B. Huttner, Andrej Shevchenko, Anthony A. Hyman Nature Cell Biology, 2013
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia Mikołaj Słabicki, Mirko Theis, Dragomir B. Krastev, Sergey Samsonov, Emeline Mundwiller, Magno Junqueira, Maciej Paszkowski-Rogacz, Joan Teyra, Anne-Kristin Heninger, Ina Poser, Fabienne Prieur, Jérémy Truchetto, Christian Confavreux, Cécilia Marelli, Alexandra Durr, Jean Philippe Camdessanche, Alexis Brice, Andrej Shevchenko, M. Teresa Pisabarro, Giovanni Stevanin, Frank Buchholz Plos Biology, 2010
A Genome-Scale RNAi Screen for Oct4 Modulators Defines a Role of the Paf1 Complex for Embryonic Stem Cell Identity Li Ding, Maciej Paszkowski-Rogacz, Anja Nitzsche, Mikolaj Michal Slabicki, Anne-Kristin Heninger, Ingrid de Vries, Ralf Kittler, Magno Junqueira, Andrej Shevchenko, Herbert Schulz, Norbert Hubner, Michael Xavier Doss, Agapios Sachinidis, Juergen Hescheler, Roberto Iacone, Konstantinos Anastassiadis, A. Francis Stewart, M. Teresa Pisabarro, Antonio Caldarelli, Ina Poser, Mirko Theis, Frank Buchholz Cell Stem Cell, 2009
Bothrops insularis venomics: A proteomic analysis supported by transcriptomic-generated sequence data Richard H. Valente, Patrícia R. Guimarães, Magno Junqueira, Ana Gisele C. Neves-Ferreira, Márcia R. Soares, Alex Chapeaurouge, Monique R.O. Trugilho, Ileana R. León, Surza L.G. Rocha, Ana Lucia Oliveira-Carvalho, Luciana S. Wermelinger, Denis L.S. Dutra, Luciana I. Leão, Inácio L.M. Junqueira-de-Azevedo, Paulo L. Ho, Russolina B. Zingali, Jonas Perales, Gilberto B. Domont Journal of Proteomics, 2009
Expression, purification, and circular dichroism analysis of human CDK9 Andreia Machado Leopoldino, Fernanda Canduri, Hamilton Cabral, Magno Junqueira, Alessandra Bernadete Trovó de Marqui, Luciano H. Apponi, Isabel Osório da Fonseca, Gilberto Barbosa Domont, Diógenes S. Santos, Sandro Valentini, Gustavo Orlando Bonilla-Rodriguez, Marcelo Andrés Fossey, Walter Filgueira de Azevedo, Eloiza Helena Tajara Protein Expression and Purification, 2006
Differential proteomic serum pattern of low molecular weight proteins expressed by adenocarcinoma lung cancer patients Journal of Experimental Therapeutics and Oncology, 2005
RECENT SCHOLAR PUBLICATIONS
Urine‐Derived iPSC Neurospheres Uncover Proteomic Correlates of Clinical Severity in Dravet Syndrome M Martins, G Nugue, A Aguiar, LRQ Souza, PV Abrantes, JR Trajano, ... Journal of Neurochemistry 170 (5), e70452 , 2026 2026
Opt-TMT: An optimized and scaled-down TMT labeling strategy for limited sample GN Michele Martins , Fábio César Sousa Nogueira, Magno Junqueira Journal of Proteomics- https://doi.org/10.1016/j.jprot.2025.105576 324 … , 2026 2026
The effect of aging on post-translational modifications of wild-type human SOD1 and the A5V ALS mutant GF de Souza, RSS Magalhães, JRM Neto, M Martins, C Follmer, ... bioRxiv, 2025.06. 02.657411 , 2025 2025
Optimized pipeline for personalized neurobiological insights from single patient-derived Neurospheres G Nugue, M Martins, G Vitória, BLDML Guimaraes, M Quiñones-Vega, ... Journal of Proteomics 313, 105368 , 2025 2025 Citations: 3
Cry1Ac toxin binding in the velvetbean caterpillar Anticarsia gemmatalis : study of midgut aminopeptidases N MD Lanzaro, I Padilha, LFC Ramos, APG Méndez, A Menezes, YM Silva, ... Frontiers in Physiology 15, 1484489 , 2024 2024 Citations: 2
Lysergic acid diethylamide induces behavioral changes in Caenorhabditis elegans IM Ornelas, BS Carrilho, MAVC Ventura, I Domith, CMV Silveira, ... Neuroscience Letters 837, 137903 , 2024 2024 Citations: 2
Systematic characterization of Lysergic Acid Diethylamide metabolites in Caenorhabditis elegans by ultra-high performance liquid chromatography coupled with high-resolution … CM de Vasconcellos Silveira, VF Dos Santos, IM Ornelas, ... Journal of Chromatography A 1708, 464362 , 2023 2023 Citations: 2
Quantitative proteomics analysis of single brain organoids and patient-derived neurospheres using TMT10plex isobaric tags M Junqueira BRAIN PATHOLOGY 33 , 2023 2023
Systematic Characterization of LSD metabolites in C. elegans by ultra-high performance liquid chromatography coupled with high-resolution tandem mass … CMV Silveira, VF dos Santos, IM Ornelas, BS Carrilho, MAVC Ventura, ... bioRxiv, 2023.06. 19.545563 , 2023 2023
The application of OMICS technologies to interrogate host-virus interactions F Gomes, K Alfson, M Junqueira Frontiers in Cellular and Infection Microbiology 12, 1050012 , 2022 2022 Citations: 2
Interspecies Isobaric Labeling-Based Quantitative Proteomics Reveals Protein Changes in the Ovary of Aedes aegypti Coinfected With ZIKV and Wolbachia LFC Ramos, M Martins, JR Murillo, GB Domont, DMP de Oliveira, ... Frontiers in Cellular and Infection Microbiology 12, 900608 , 2022 2022 Citations: 6
EhRho6‐mediated actin degradation in Entamoeba histolytica is associated with compromised pathogenicity AR Narooka, A Apte, P Yadav, JR Murillo, L Goto‐Silva, M Junqueira, ... Molecular microbiology 117 (5), 1121-1137 , 2022 2022 Citations: 5
Quantitative profiling of axonal guidance proteins during the differentiation of human neurospheres L Goto-Silva, M Martins, JR Murillo, LRQ Souza, G Vitória, JT Oliveira, ... Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1869 (8), 140656 , 2021 2021 Citations: 10
Single-cell proteomics: A treasure trove in neurobiology L Goto-Silva, M Junqueira Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1869 (7), 140658 , 2021 2021 Citations: 31
Identification of Potentially Therapeutic Immunogenic Peptides From Paracoccidioides lutzii Species LBR Silva, CL Taira, LG Cleare, M Martins, M Junqueira, JD Nosanchuk, ... Frontiers in immunology 12, 670992 , 2021 2021 Citations: 10
Comprehensive Quantitative Proteome Analysis of Aedes aegypti Identifies Proteins and Pathways Involved in Wolbachia pipientis and Zika Virus Interference … M Martins, LFC Ramos, JR Murillo, A Torres, SS de Carvalho, GB Domont, ... Frontiers in Physiology 12, 642237 , 2021 2021 Citations: 27
Computational fluid dynamic analysis of physical forces playing a role in brain organoid cultures in two different multiplex platforms L Goto-Silva, NME Ayad, IL Herzog, NP Silva, B Lamien, HRB Orlande, ... BMC developmental biology 19 (1), 3 , 2019 2019 Citations: 65
Extracellular vesicles and vesicle-free secretome of the protozoa Acanthamoeba castellanii under homeostasis and nutritional stress and their damaging potential … DS Gonçalves, MS Ferreira, SC Liedke, KX Gomes, GA de Oliveira, ... Virulence 9 (1), 818-836 , 2018 2018 Citations: 63
Mass spectrometry evaluation of a neuroblastoma SH-SY5Y cell culture protocol JR Murillo, I Pla, L Goto-Silva, FCS Nogueira, GB Domont, ... Analytical Biochemistry 559, 51-54 , 2018 2018 Citations: 6
Computational fluid dynamic analysis reveals the underlying physical forces playing a role in 3D multiplex brain organoid cultures L Goto-Silva, NME Ayad, IL Herzog, NP Silva, B Lamien, HRB Orlande, ... bioRxiv, 369082 , 2018 2018
MOST CITED SCHOLAR PUBLICATIONS
A genome-scale RNAi screen for Oct4 modulators defines a role of the Paf1 complex for embryonic stem cell identity L Ding, M Paszkowski-Rogacz, A Nitzsche, MM Slabicki, AK Heninger, ... Cell stem cell 4 (5), 403-415 , 2009 2009 Citations: 331
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia M Słabicki, M Theis, DB Krastev, S Samsonov, E Mundwiller, M Junqueira, ... PLoS biology 8 (6), e1000408 , 2010 2010 Citations: 248
Dbf4-dependent CDC7 kinase links DNA replication to the segregation of homologous chromosomes in meiosis I J Matos, JJ Lipp, A Bogdanova, S Guillot, E Okaz, M Junqueira, ... Cell 135 (4), 662-678 , 2008 2008 Citations: 230
Motor-independent targeting of CLASPs to kinetochores by CENP-E promotes microtubule turnover and poleward flux S Maffini, ARR Maia, AL Manning, Z Maliga, AL Pereira, M Junqueira, ... Current Biology 19 (18), 1566-1572 , 2009 2009 Citations: 149
Characterization of rhamnolipids produced by wild-type and engineered Burkholderia kururiensis LFD Tavares, PM Silva, M Junqueira, DCO Mariano, FCS Nogueira, ... Applied microbiology and biotechnology 97 (5), 1909-1921 , 2013 2013 Citations: 134
Comparative profiling identifies C13orf3 as a component of the Ska complex required for mammalian cell division M Theis, M Slabicki, M Junqueira, M Paszkowski-Rogacz, J Sontheimer, ... The EMBO Journal 28 (10), 1453 , 2009 2009 Citations: 131
Differential proteomic serum pattern of low molecular weight proteins expressed by adenocarcinoma lung cancer patients. CM Maciel, M Junqueira, MEM Paschoal, MT Kawamura, RLM Duarte, ... Journal of experimental therapeutics & oncology 5 (1) , 2005 2005 Citations: 120
A genomic toolkit to investigate kinesin and myosin motor function in cells Z Maliga, M Junqueira, Y Toyoda, A Ettinger, F Mora-Bermudez, ... Nature cell biology 15 (3), 325-334 , 2013 2013 Citations: 117
A systematic RNAi synthetic interaction screen reveals a link between p53 and snoRNP assembly DB Krastev, M Slabicki, M Paszkowski-Rogacz, NC Hubner, M Junqueira, ... Nature cell biology 13 (7), 809-818 , 2011 2011 Citations: 97
Bothrops insularis venomics: A proteomic analysis supported by transcriptomic-generated sequence data RH Valente, PR Guimarães, M Junqueira, AGC Neves-Ferreira, ... Journal of proteomics 72 (2), 241-255 , 2009 2009 Citations: 96
Protein identification pipeline for the homology-driven proteomics M Junqueira, V Spirin, TS Balbuena, H Thomas, I Adzhubei, S Sunyaev, ... Journal of proteomics 71 (3), 346-356 , 2008 2008 Citations: 93
Quantitative proteomic analysis identifies proteins and pathways related to neuronal development in differentiated SH-SY5Y neuroblastoma cells JR Murillo, L Goto-Silva, A Sánchez, FCS Nogueira, GB Domont, ... EuPA open proteomics 16, 1-11 , 2017 2017 Citations: 84
Changes in the 2-DE protein profile during zygotic embryogenesis in the Brazilian Pine (Araucaria angustifolia) TS Balbuena, V Silveira, M Junqueira, LLC Dias, C Santa-Catarina, ... Journal of Proteomics 72 (3), 337-352 , 2009 2009 Citations: 83
An in-depth snake venom proteopeptidome characterization: Benchmarking Bothrops jararaca CA Nicolau, PC Carvalho, ILM Junqueira-de-Azevedo, A Teixeira-Ferreira, ... Journal of proteomics 151, 214-231 , 2017 2017 Citations: 80
Differential proteome analysis of mature and germinated embryos of Araucaria angustifolia TS Balbuena, L Jo, FP Pieruzzi, LLC Dias, V Silveira, C Santa-Catarina, ... Phytochemistry 72 (4-5), 302-311 , 2011 2011 Citations: 68
Computational fluid dynamic analysis of physical forces playing a role in brain organoid cultures in two different multiplex platforms L Goto-Silva, NME Ayad, IL Herzog, NP Silva, B Lamien, HRB Orlande, ... BMC developmental biology 19 (1), 3 , 2019 2019 Citations: 65
Extracellular vesicles and vesicle-free secretome of the protozoa Acanthamoeba castellanii under homeostasis and nutritional stress and their damaging potential … DS Gonçalves, MS Ferreira, SC Liedke, KX Gomes, GA de Oliveira, ... Virulence 9 (1), 818-836 , 2018 2018 Citations: 63
A further proteomic study on the effect of iron in the human pathogen Trichomonas vaginalis JB De Jesus, P Cuervo, M Junqueira, C Britto, F Costa e Silva‐Filho, ... Proteomics 7 (12), 1961-1972 , 2007 2007 Citations: 60
Tools for exploring the proteomosphere A Shevchenko, CM Valcu, M Junqueira Journal of proteomics 72 (2), 137-144 , 2009 2009 Citations: 59
Proteome analysis of Leishmania (Viannia) braziliensis by two-dimensional gel electrophoresis and mass spectrometry P Cuervo, JB de Jesus, M Junqueira, L Mendonça-Lima, LJ González, ... Molecular and biochemical parasitology 154 (1), 6-21 , 2007 2007 Citations: 59
