Visite nosso website oficial:

https://www.iq.usp.br/marcelodasilva/

INFORMAÇÕES SOBRE PESQUISA / RESEARCH INFORMATION

Área(s) de Pesquisa / Research Area(s):

- Biologia Molecular e Celular de Tripanosomatídeos/ Molecular and Cellular Biology of Trypanosomatids

- Bioquímica de Doenças Tropicais Negligenciadas/ Biochemistry of Tropical Neglected Diseases

Tema da Pesquisa / Research Topics: 

- Metabolismo de DNA com foco em replicação, reparo e ciclo celular/ DNA metabolism focusing on replication, repair and cell cycle

- Pirofosforilação por Pirofosfatos de Inositol / Pyrophosphorylation by Inositol Pyrophosphates

   CV Lattes                   ORCID               Publons-Web of Science 

Pesquisa / Research:

The leading interest of our laboratory is to understand the main aspects related to DNA metabolism in trypanosomatids etiological agents of neglected tropical diseases, i.e., Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei. The DNA metabolism in these organisms is unique in many ways (presence of a divergent pre-replication complex, presence of base J, absence of the canonical DNA repair pathway non-homologous end joining – cNHEJ), and we are trying to better understand these peculiarities through in silico, in vitro, and in vivo molecular approaches. We have focused on (i) kinases involved in inositol pyrophosphates synthesis, (ii) inositol pyrophosphates targets (iii) the role of pyrophosphorylation during the cell cycle and DNA repair pathways, (iv) DNA replication origins usage. We are also interested in the evolution and biodiversity of Euglenozoa group, as well as parasitism emergence within kinetoplastids. Moreover, we are also interested in developing potential effective drugs to combat leishmaniasis and Chagas disease.

Grupo / Group:

We are a very young research group that originated from a Young Research Grant (from São Paulo Research Foundation – FAPESP) in 2020. Due to the interdisciplinary nature of our research, we have had intense interaction with collaborating groups worldwide.

Membros atuais / Lab members:

- Bryan Etindi Abuchery (MSc student)

- Marcos Antônio Fernandes de Oliveira (MSc student)

- Vitor Luiz da Silva (PhD candidate)

- Thaise Lara Teixeira (Postdoc)

Lab Alumni:

- Arthur de Oliveira Passos (MSc)

- Yete Gambarini Ferri (MSc)

Laboratório e confraternizações / Laboratory and get-togethers:

Videos:

https://www.youtube.com/watch?v=Gx80aMACqK8&t=1s

Entrevistas / Interviews:

Agência FAPESP:

https://agencia.fapesp.br/combate-a-pandemia-ensina-licoes-para-erradicacao-das-doencas-tropicais-negligenciadas/35136/

https://agencia.fapesp.br/fenomeno-que-normalmente-leva-celulas-humanas-a-morte-parece-ser-vital-para-parasitas-aponta-estudo/38260/

Jornal UNESP:

https://jornal.unesp.br/2022/01/14/da-periferia-a-pesquisa-de-ponta-a-trajetoria-de-um-jovem-pesquisador-na-unesp/

News Bulletin:

https://newsbulletin247.com/technology/73718.html

Titulares:

https://titulares.ar/el-fenomeno-que-lleva-a-las-celulas-humanas-a-la-muerte-parece-ser-vital-para-los-parasitos-segun-un-estudio-04-05-2022-ciencia-brasil/

News today24:

https://news.today24.news/news/136327.html

Labnetwork:

https://www.labnetwork.com.br/noticias/fenomeno-que-normalmente-leva-celulas-humanas-a-morte-parece-ser-vital-para-parasitas-aponta-estudo/

Folha:

https://www1.folha.uol.com.br/ciencia/2022/04/fenomeno-que-leva-celulas-humanas-a-morte-parece-ser-vital-para-parasitas-aponta-estudo.shtml

Veja:

https://veja.abril.com.br/saude/fenomeno-que-leva-as-celulas-humanas-a-morte-pode-ser-vital-para-parasitas/

Saber Atualizado News:

https://www.saberatualizadonews.com/2022/04/fenomeno-geralmente-letal-para-as.html

Publicações / Publications:

2023:

. DA SILVA, M. S., VITARELLI, M. O., VIALA, V. L., TSANTARLIS, K., PIRES, D. S., FRANCO, T. A., DE AZEVEDO, I. L. M. J., ELIAS, M. C., TONELLI, R. R. (2023). Clues on the dynamics of DNA replication in Giardia lamblia. Journal of Cell Science, jcs.260828. DOI: 10.1242/jcs.260828.

2022:

. DA SILVA, M. S., MCCULLOCH, R., and CANO, M. I. N. (2022). Editorial: Nuclear Genome Stability: DNA Replication, Telomere Maintenance, and DNA Repair. Frontiers in Cell and Developmental Biology, 10:875749. DOI: 10.3389/fcell.2022.875749.

. ABUCHERY, B. E., BLACK, J. A., and DA SILVA, M. S. (2022). Single-cell transcriptomics reveals hidden information in trypanosomatids. Trends in Parasitology, 38(1), 4-6. DOI: 10.1016/j.pt.2021.10.006.

. TEIXEIRA, S. C., DA SILVA, M. S., et al. (2022) Panacea within a Pandora's box: The antiparasitic effects of phospholipases A2 (PLA2s) from snake venoms. Trends in Parasitology, 38(1):80-94. DOI: 10.1016/j.pt.2021.07.004.

- (BOOK) CANO, M. I. N.; MCCULLOCH, R.; DA SILVA, M.S. (2022) Nuclear Genome Stability: DNA Replication, Telomere Maintenance, and DNA Repair. 1°ed. Lausanne: Frontiers Media SA, 2022. v. 1. 292p. DOI: 10.3389/978-2-88974-630-9. ISBN 978-2-88974-630-9. ISSN 1664-8714.

- (BOOK CHAPTER) PASSOS, A. O., ASSIS, L. H. C., FERRI, Y. G., SILVA, V. L., DA SILVA, M. S., CANO, M. I. N. (2022) The trypanosomatids cell cycle: a brief report. In: SPRINGER NATURE, Methods in Molecular Biology (in press).

- (BOOK CHAPTER) OLIVEIRA, B. C. D., ASSIS, L. A. H., SHIBURAH, M. E., PAIVA, S. C., FONTES, V. S., DE OLIVEIRA, L. S., SILVA, V. L., DA SILVA, M. S., CANO, M. I. N. (2022) Synchronization of Leishmania amazonensis cell cycle using hydroxyurea. In: SPRINGER NATURE, Methods in Molecular Biology (in press).

2021:

. ASSIS, L. H., ANDRADE-SILVA, D., SHIBURAH, M. E., DE OLIVEIRA, B. C., PAIVA, S. C., ABUCHERY, B. E., FERRI, Y. G., FONTES, V. S., OLIVEIRA, L. S., DA SILVA, M. S., and CANO, M. I. N. (2021). Cell Cycle, Telomeres, and Telomerase in Leishmania spp.: What Do We Know So Far? Cells, 10(11), 3195. DOI: 10.3390/cells10113195.

. OLIVEIRA, B. C. D., SHIBURAH, M. E., PAIVA, S. C., VIEIRA M. R., MOREA, E. G. O., DA SILVA, M. S., et al., (2021) Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation. Frontiers in Cell and Developmental Biology, 2951. DOI: 10.3389/fcell.2021.713415.

. DA SILVA, M. S., (2021) DNA double-strand breaks: A double-edged sword for trypanosomatids. Frontiers in Cell and Developmental Biology, 9, 945. DOI: 10.3389/fcell.2021.669041.

. COSTA-SILVA, H. M., RESENDE, B. C., UMAKI, A., PRADO, W., DA SILVA, M.S., et al., (2021) DNA topoisomerase 3α is involved in homologous recombination repair and replication stress response in Trypanosoma cruzi. Frontiers in Cell and Developmental Biology, 9, 849. DOI: 10.3389/fcell.2021.633195.

. CARARO-LOPES, E., DIAS, M. H., DA SILVA, M. S., et al., (2021) Autophagy buffers Ras-induced genotoxic stress enabling malignant transformation in keratinocytes primed by human papillomavirus. Cell death & disease, 12(2), 1-16. DOI: 10.1038/s41419-021-03476-3.

2020:

. MARÍN, P. A., OBONAGA, R., PAVANI, R. S., DA SILVA, M. S., et al., (2020) ATR kinase is a crucial player mediating the DNA damage response in Trypanosoma brucei. Frontiers in Cell and Developmental Biology, 8, 1951. DOI: 10.3389/fcell.2020.602956.

. DA SILVA, M. S. (2020) Estimation of the Minimum Number of Replication Origins Per Chromosome in any Organism. Bio-protocol, 10(20): e3798. DOI: 10.21769/BioProtoc.3798.

. DA SILVA, M. S., et al., (2020) Cytotoxic and genotoxic effects on human keratinocytes triggered by sphingomyelinase D from Loxosceles venom. Archives of Toxicology, 94(10): 3563-3577. DOI: 10.1007/s00204-020-02830-2.

. DA SILVA, M. S., et al., (2020) Comparative Analysis of the Minimum Number of Replication Origins in Trypanosomatids and Yeasts. Genes, 11(5): 523. DOI: 10.3390/genes11050523.

. NUNES, V. S., MORETTI, N. S., DA SILVA, M. S., et al. (2020) Trimethylation of histone H3K76 by Dot1B enhances cell cycle progression after mitosis in Trypanosoma cruzi. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1867(7): 118694. DOI: 10.1016/j.bbamcr.2020.118694.

- (BOOK CHAPTER) DA SILVA, M. S. (2020) Uma Breve Síntese Sobre o Ciclo Celular de Parasitos Tripanosomatídeos. In: Atualidades em Medicina Tropical no Brasil: Protozoários. 1ed. Rio Branco: Stricto Sensu Editora, (1):12-28. DOI: 10.35170/ss.ed.9786586283136.01.

2019:

. DA SILVA, M. S., CAYRES-SILVA, G., VITARELLI, M.O., MARIN, P. A., HIRAIWA, P. M., ARAÚJO, C. B., SCHOLL, B. B., ÁVILA, A. R., McCULLOCH, R., REIS, M. S., and ELIAS, M. C. (2019) Transcription activity contributes to the firing of non-constitutive origins in African trypanosomes helping to maintain robustness in S-phase duration. Scientific Reports 9(1):18512. DOI: 10.1038/s41598-019-54366-w.

. CUEVAS-HERNÁNDEZ, R., GIRARD, R., MARTÍNEZ-CERÓN, S., DA SILVA, M. S., et al., (2019) A fluorinated phenylbenzothiazole arrest the Trypanosoma cruzi cell cycle and diminishes the mammalian host-cell infection. Antimicrobial Agents and Chemotherapy pii: AAC.01742-19. DOI: 10.1128/AAC.01742-19.

. TEIXEIRA, T. L., CASTILHOS, P., RODRIGUES, C. C., SILVA, A. A., BRIGIDO, R. T. S., TEIXEIRA, S. C., BORGES, B. C., SANTOS, M. A., MARTINS, F. A., SANTOS, P. C. F., SERVATO, J. P. S., DA SILVA, M.S. et al., (2019) Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection. Microbial Pathogenesis, 135: 103618. DOI: 10.1016/j.micpath.2019.103618.

. TEIXEIRA, S. C., LOPES, D. S., DA SILVA, M. S., et al., (2019) Pentachloropseudilin Impairs Angiogenesis by Disrupting Actin Cytoskeleton, Integrin Trafficking and Cell Cycle. ChemBioChem, 20: 1-13. DOI: 10.1002/cbic.201900203.

. FERNANDES, C. A. H., PEREZ, A. M., BARROS, A. C., DREYER, T. R., DA SILVA, M. S., MOREA, E. G. O. et al., (2019) Dual cellular localization of the Leishmania amazonensis Rbp38 (LaRbp38) explains its affinity for telomeric and mitochondrial DNA. Biochimie, 162:15-25. DOI: 10.1016/j.biochi.2019.03.017.

. COSTA, M.S., GONÇALVES, Y. G., TEIXEIRA, S. C., NUNES, D. C. O., LOPES, D. S., SILVA, C. V., DA SILVA, M. S., et al., (2019) Increased ROS generation causing apoptotic-like death and autophagy: mechanistic insights into the anti-Leishmania activity of apotent ruthenium (II) complex. Journal of Inorganic Biochemistry, 195:1-12. DOI: 10.1016/j.jinorgbio.2019.03.005.

. POLLONI, L., GOULART, L., CORREIA, L. I., SILVA, A. C. S., DA SILVA, M. S., et al., (2019) Action of copper (II) complex with β-diketone and 1,10-phenanthroline (CBP-01) on sarcoma cells and biological effects under cell death. Biomedicine and pharmacotherapy, 112:108586. DOI: 10.1016/j.biopha.2019.01.047.

. LIMA, L. O., CALDERANO, S., DA SILVA, M. S., ARAÚJO, C. B., et al., (2019) Orthologue of the helicase domain of polymerase Theta modulates DNA replication in Trypanosoma cruzi. Scientific Reports 9(1):2888. DOI: 10.1038/s41598-019-39348-2.

. TAVERNELLI, L. E., MOTTA, M. C. M., GONÇALVES, C. S., DA SILVA, M. S., ELIAS, M. C., ALONSO, V. L., SERRA, E., CRIBB, P. (2019) Overexpression of Trypanosoma cruzi High Mobility Group B protein (TcHMGB) alters the nuclear structure, impairs cytokinesis and reduces the parasite infectivity. Scientific Reports, 9 (192) DOI: 10.1038/s41598-018-36718-0.

2018:

. DA SILVA M. S., HOVEL-MINER, G., BRIGGS, E., ELIAS, M. C., and MCCULLOCH, R. (2018) Evaluation of mechanisms that may generate DNA lesions triggering antigenic variation in African trypanosomes. PLoS Pathogens 14(11): e1007321. DOI: 10.1371/journal.ppat.1007321.

. DA SILVA, M. S., MARIN, P. A., REPOLÊS, B. M., ELIAS, M. C., and MACHADO, C. R. (2018) Analysis of DNA Exchange Using Thymidine Analogs (ADExTA) in Trypanosoma cruzi. Bio-protocol. 8(24): e3125. DOI: 10.21769/BioProtoc.3125.

. DIAS, M. H., FONSECA, C. S., ZEIDLER, J. D., ALBUQUERQUE, L. L., DA SILVA, M. S., LOPES‐CARARO, E., REIS, M. S., NOËL, V., DOS SANTOS, E. O., PRIOR, I. A. and ARMELIN, H. A. (2018) Fibroblast Growth Factor 2 lethally sensitizes cancer cells to stress‐targeted therapeutic inhibitors. Molecular Oncology. 13(2):290-306. DOI: 10.1002/1878-0261.12402.

. ALVES, C.L., REPOLÊS, B. M., DA SILVA, M. S., MENDES, I. C., et al., (2018) The recombinase Rad51 plays a key role in events of genetic exchange in Trypanosoma cruzi. Scientific Reports, 8(1):13335. DOI: 10.1038/s41598-018-31541-z.

. SILVA, M. A., LOPES, D., TEIXEIRA, S. C., GIMENES, S., AZEVEDO, F. V. P. V., POLLONI, L., BORGES, B. C., DA SILVA, M.S., et al., (2018). Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells. International Journal of Biological Macromolecules, 118(Pt A):311-319. DOI: 10.1016/j.ijbiomac.2018.06.082.

. MARIN, P. A., DA SILVA, M. S., PAVANI, R. S., MACHADO, C. R., and ELIAS, M. C. (2018). Recruitment kinetics of the homologous recombination pathway in procyclic forms of Trypanosoma brucei after ionizing radiation treatment. Scientific reports, 8(1), 5405. DOI: 10.1038/s41598-018-23731-6.

2017:

. DA SILVA, M. S., SEGATTO, M., PAVANI, R. S., et al., (2017a) Consequences of acute oxidative stress in Leishmania amazonensis: From telomere shortening to the selection of the fittest parasites. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1864(1), 138-150. DOI: 10.1016/j.bbamcr.2016.11.001.

. DA SILVA, M. S., MUÑOZ, P. A. M., ARMELIN, H. A., and ELIAS, M. C. (2017b). Differences in the Detection of BrdU/EdU Incorporation Assays Alter the Calculation for G1, S, and G2 Phases of the Cell Cycle in Trypanosomatids. Journal of Eukaryotic Microbiology, 64(6), 756-770. DOI: 10.1111/jeu.12408.

. DA SILVA, M. S., PAVANI, R. S., DAMASCENO J.D. et al., (2017c) Nuclear DNA replication in trypanosomatids: there are no easy methods for solving difficult problems. Trends in Parasitology, 33(11):858-874. DOI: 10.1016/j.pt.2017.08.002.

. MOREA, E. G. O., VIVIESCAS, M. A., FERNANDES, C. A. H., MATIOLI, F. F., LIRA, C. B. B., FERNANDEZ, M. F., MORAES, B. S., DA SILVA, M. S., et al., (2017) A calmodulin-like protein (LCALA) is a new Leishmania amazonesis candidate for telomere end-binding protein. Biochimica et Biophysica Acta (BBA) - General Subjects, 1861, 2583–97. DOI: 10.1016/j.bbagen.2017.08.011.

. TEIXEIRA, S. C., LOPES, D. S., GIMENES, S. N., TEIXEIRA, T. L., DA SILVA, M. S. et al., (2017) Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy. Scientific Reports, 7, 44978. DOI: 10.1038/srep44978.

- (BOOK) DA SILVA, M. S. and CANO, M.I.N. – editores (2017) Frontiers in Parasitology: Molecular and Cellular Biology of Pathogenic Trypanosomatids. 1° edition. Bentham Science Publishers. DOI: 10.2174/97816810840531170101. ISBN 978-1-68108-406-0. ISSN 2542-4211 (Print). ISSN 2542-422X (Online).

- (BOOK CHAPTER) DA SILVA, M. S.; VIVIESCAS, M. A.; PAVANI, R. S. et al., (2017) Nuclear and Kinetoplast DNA Replication in Trypanosomatids. In: Molecular and Cellular Biology of Pathogenic Trypanosomatids.1 ed., Bentham e-books, v.1, p. 134-194.

- (BOOK CHAPTER) CALDERANO, S. G.; MORETTI, N. S.; ARAUJO, C. B., DA SILVA, M. S. et al., (2017) The Cellular Organization of Trypanosomatids During Life Cycle. In: Molecular and Cellular Biology of Pathogenic Trypanosomatids. 1 ed., Bentham e-books, v.1, p. 3-60.

2016:

. PAVANI, R. S., DA SILVA, M. S., FERNANDES, C. A. H. et al., (2016) Replication Protein A Presents Canonical Functions and Is Also Involved in the Differentiation Capacity of Trypanosoma cruzi. PLoS Neglected Tropical Diseases, 10, e0005181. DOI: 10.1371/journal.pntd.0005181.

. GIRARD, R. M.; CRISPIM, M.; STOLIĆ, I.; DAMASCENO, F. S.; DA SILVA, M. S. et al., (2016) An Aromatic Diamidine That Targets Kinetoplast DNA, Impairs the Cell Cycle in Trypanosoma cruzi, and Diminishes Trypomastigote Release from Infected Mammalian Host Cells. Antimicrobial Agents and Chemotherapy, 60(10), 5867-5877. DOI: 10.1128/AAC.01595-15.

2014:

. VASCONCELOS, E. J. R.; NUNES, V. S.; DA SILVA, M. S. et al., (2014) The Putative Leishmania Telomerase RNA (LeishTER) Undergoes Trans-Splicing and Contains a Conserved Template Sequence. Plos One, v9, e112061. DOI: 10.1371/journal.pone.0112061.

. GIARDINI, M. A., SEGATTO, M., DA SILVA, M. S., et al., (2014) Telomere and telomerase biology. In: Progress in Molecular Biology and Translational Science, 1ed., Elsevier, 125:1-40. DOI: 10.1016/B978-0-12-397898-1.00001-3.

2013:

. DA SILVA, M.S., MONTEIRO, J.P., NUNES, V.S., et al., (2013) Leishmania amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation during cell cycle. PLoS One. 8(11), e81397. DOI: 10.1371/journal.pone.0081397.

. DA SILVEIRA, R.C.V., DA SILVA, M.S., NUNES, V.S., et al. (2013) The natural absence of RPA1N domain did not impair Leishmania amazonensis RPA-1 participation in DNA damage response and telomere protection. Parasitology, 140, 547–559. DOI: 10.1017/S0031182012002028.

2012:

- (BOOK CHAPTER) DA SILVA, M. S.; da SILVEIRA, R. C. V.; PEREZ, A. M., et al., (2012) Nuclear DNA Replication in Trypanosomatid Protozoa. In: DNA Replication and Mutation. 1ed. Nova Science Publishers, 1:123-178.

2010:

. DA SILVA, M.S., PEREZ, A.M., DA SILVEIRA, R.C.V., et al., (2010) The Leishmania amazonensis TRF (TTAGGG repeat-binding factor) homologue binds and co-localizes with telomeres. BMC Microbiology, 10:136. DOI: 10.1186/1471-2180-10-136.