Welcome to the main page of the Laboratory of Gene Expression in Eukaryotes headed by Prof. Sergio Verjovski-Almeida. Our lab is located in a beautiful sunny city São Paulo, Brazil. Look below to find out more about us, our research, open positions and publications.

HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines

In this work we for the first time systematically explore the phenomenon of cell-to-cell variation of gene expression and link it to low population-level expression of lncRNAs, showing that, similar to HIPSTR, a novel antisense lncRNA identified in this study, the expression of lncRNAs is more highly heterogeneous than of mRNAs in otherwise indistinguishable cells of totipotent human embryos, primordial germ cells, and stable cell lines.


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Here is what we study:


Human gene expression

Background. 2004-2008. Our project entitled ″Identification of molecular markers for diagnosis and prognosis in cancer using DNA microarrays″, has identified dozens of intronic non-coding anti-sense RNAs (ncRNAs) whose expression levels were correlated to the degree of malignancy of prostate tumors (Reis et al., 2004; PMID: 15221013). This discovery has an impact on the molecular diagnosis of cancer in general, arguing for inclusion of non-coding RNAs, both intra- and inter-genic, into the arsenal of tools used for molecular diagnostics, so far almost exclusively populated by exonic protein-coding RNAs.

In our project we have also identified that:

- the expression profiles of intronic ncRNAs in normal human liver and kidney tissues and in prostate tumors, using customized microarrays with nearly 30 thousand probes for non-coding intronic RNAs. It was observed that the most abundant intronic ncRNAs are transcribed from genomic loci involved with regulation of transcription, in all three tissues studied (Nakaya et al., 2007; PMID: 17386095);

- that the expression of a number of intronic ncRNAs could be modulated by androgen in a prostate cancer cell line, and that androgen modulates both the expression level of certain ncRNAs and the use of alternatively spliced exons of protein-coding genes from the same genomic locus (Louro et al., 2007; PMID: 17263875);

- that a comparative analysis between human and mice intronic ncRNAs revealed a conserved tissue-specific expression profile, suggesting an evolutionarily conserved role of these transcripts among these species, probably involved in the fine tuning of gene expression in mammalian tissues (Louro et al., 2008; PMID: 18495418).


Current studies. In August 2008, our group received a new grant from FAPESP for the period 2008-2012. The current thematic project is titled ″Functional characterization of intronic non-coding RNAs expressed in the human genome″, a collaborative project between our group and the research group of Dr. Eduardo M. Reis, an Assistant Professor in our Department. The project aims to investigate the functional implications of intronic ncRNAs in cancer as well as in gene regulation in normal cells, along with their possible use as markers of malignancy in a number of cancers. The present project will permit to consolidate in our group the use of cell biology approaches for the study of ncRNAs, a line of work that has been recently introduced in our laboratory. Currently, our group is studying the effect of over-expression of selected ncRNAs on cell proliferation and cell invasion.

The project is divided into two major parts:

(A) Functional characterization of non-coding RNAs over-expressed in human tumors, and
(B) Identification of novel non-coding RNAs and validation of gene expression profiles as possible tumor markers.

We expect to identify genes that are possible new molecular markers of early diagnosis and prognosis in prostate cancer, as well as to elucidate some of the mechanisms of action of ncRNAs, contributing to broaden the potential targets for therapeutic interventions.

Publications
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Schistosoma mansoni gene expression

Schistosoma mansoni EST genome. Our group has received support from FAPESP to build DNA microarrays on glass-slides containing 4 000 S. mansoni gene fragments. See the project here. These were selected among the 14 000 genes that were identified by the S. mansoni EST Genome Project, coordinated by our group, whose results were published in Nature Genetics on October 1st, 2003 (download PDF; PMID: 12973350).

One of our first goals will be to use microarrays to do large-scale gene expression analysis in adult worms and to study the effect of hormones and cytokines. Gene expression pattern during S. mansoni development and maturation from cercaria to schistosomula will also be studied. Collaboration with other research groups worldwide is envisaged.


Schistosoma mansoni TNF-α receptor. We have recently described (Oliveira et al., 2009; PMID: 19956564) a possible TNF-α receptor (TNFR) homolog gene in S. mansoni (SmTNFR). SmTNFR encodes a complete receptor sequence composed of 599 amino acids, and contains four cysteine-rich domains as described for TNFR members.

Real-time RT-PCR experiments revealed that SmTNFR highest expression level is in cercariae, 3.5 (60.7) times higher than in adult worms. Downstream members of the known human TNF-α pathway were identified by an in silico analysis, revealing a possible TNF-α signaling pathway in the parasite. In order to simulate parasite's exposure to human cytokine during penetration of the skin, schistosomula were exposed to human TNF-α just 3 h after cercariae-to-schistosomula in vitro transformation, and large-scale gene expression measurements were performed with microarrays. A total of 548 genes with significantly altered expression were detected, when compared to control parasites. In addition, treatment of adult worms with TNF-α caused a significantly altered expression of 1857 genes. Interestingly, the set of genes altered in adults is different from that of schistosomula, with 58 genes in common, representing 3% of altered genes in adults and 11% in 3 h-old early schistosomula. The possible molecular elements and targets involved in human TNF-α effect on S. mansoni were described, highlighting the mechanism by which recently transformed schistosomula may sense and respond to this host mediator at the site of cercarial penetration into the skin.

Our present work aims at further characterizing the receptor by its immuno-localization at different organs of the parasite, by searching for possible partner protein ligands with the use of two-hybrid systems, by looking for the possible effect of siRNA of the receptor message on parasite survival in the model host.

Publications
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Bioinformatics

Our group developed competence in bioinformatics to support the large scale transcriptome sequencing and analyses projects of both humans and S. mansoni. Our team of bioinformaticians is composed of technicians with higher degree in computer sciences and graduate students in bioinformatics. They work in the large scale mapping of all human ESTs in the genome, in order to select transcribed genes of interest to be selected as probes for the construction of dedicated microarrays. These are used in our large scale gene expression studies.

Click here to see the Bioinformatics webpage of the group.

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Meet the lab

Prof. Sergio Verjovski-Almeida

Principal investigator


Sergio Verjovski-Almeida, PhD, MD

Scientific Leadership at Butantan
Senior Full Professor at USP



Instituto Butantan
Av. Vital Brasil 1500, Predio 55
05503-900 São Paulo, SP, Brasil

e-mail 1: verjo (at) iq.usp.br
e-mail 2: sergio.verjovski (at) butantan.gov.br

phone: +55-11-2627-3850 (my office)

phone: +55-11-2627-3855 (laboratory)

Postdoctoral researchers:

  • Adriana Silva Andrade Pereira, PhD
  • Elton José Rosas Vasconcelos, PhD
  • Letícia Anderson, PhD

PhD and Master students:

  • Lucas Ferreira da Silva
  • Alexandre Videira
  • David Abraham Morales Vicente
Undergraduate students:
  • Felipe Genova Panicio
  • Vinicius Mesel

Secretary:

  • Ana Paula Lopes Vidal

Lab manager:

  • Murilo Sena Amaral, PhD

Bioinformatics Technician:

  • David da Silva Pires
  • anasap (at) iq.usp.br
  • eltonjrv (at) iq.usp.br
  • leticiaa (at) iq.usp.br
  • lucasfsilva (at) usp.br
  • videira (at) iq.usp.br
  • damvyt (at) gmail.com
  • felipe.panicio (at) usp.br
  • vinicius.mesel (at) butantan.gov.br
  • ana.vidal (at) butantan.gov.br
  • murilo.amaral (at) butantan.gov.br
  • david.pires (at) butantan.gov.br
Job openings

Positions open for undergraduate or graduate work.
E-mail your CV to verjo (at) iq.usp.br or call by phone for additional information.

Estágio de Iniciação Científica ou Pós-graduação disponível.
Mande seu CV para verjo (at) iq.usp.br ou telefone para obter mais informações.

Selected publications

Key publications on Human gene expression

HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines.
Yunusov D, Anderson L, DaSilva LF, Wysocka J, Ezashi T, Roberts RM, Verjovski-Almeida S.
Sci Rep. 2016 Sep 8;6:32753. doi: 10.1038/srep32753. PMID: 27605307


Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma.
Canevari RA, Marchi FA, Domingues MA, de Andrade VP, Caldeira JR, Verjovski-Almeida S, Rogatto SR, Reis EM.
Tumour Biol. 2016 Aug 2. PMID: 27485113


Jagged 1 Rescues the Duchenne Muscular Dystrophy Phenotype.
Vieira NM, Elvers I, Alexander MS, Moreira YB, Eran A, Gomes JP, Marshall JL, Karlsson EK, Verjovski-Almeida S, Lindblad-Toh K, Kunkel LM,
Zatz M.
Cell. 2015 Nov 19; 163(5):1204-13. PMID: 26582133


Global analysis of biogenesis, stability and sub-cellular localization of lncRNAs mapping to intragenic regions of the human genome.
Ayupe AC, Tahira AC, Camargo L, Beckedorff FC, Verjovski-Almeida S, Reis EM.
RNA Biol. 2015; 12(8):877-92. PMID: 26151857


Long non-coding RNA INXS is a critical mediator of BCL-XS induced apoptosis.
DeOcesano-Pereira C, Amaral MS, Parreira KS, Ayupe AC, Jacysyn JF, Amarante-Mendes GP, Reis EM, Verjovski-Almeida S.
Nucleic Acids Res. 2014 Sep 1; 42(13):8343-55. PMID: 27507889


Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations.
Fachel AA, Tahira AC, Vilella-Arias SA, Maracaja-Coutinho V, Gimba ER, Vignal GM, Campos FS, Reis EM, Verjovski-Almeida S.
Mol Cancer. 2013 Nov 15; 12(1):140. PMID: 24238219


Long non-coding RNAs and their implications in cancer epigenetics.
Beckedorff FC, Amaral MS, Deocesano-Pereira C, Verjovski-Almeida S.
Biosci Rep. 2013 Aug 30; 33(4). Review. PMID: 23875687


The intronic long noncoding RNA ANRASSF1 recruits PRC2 to the RASSF1A promoter, reducing the expression of RASSF1A and increasing cell proliferation.
Beckedorff FC, Ayupe AC, Crocci-Souza R, Amaral MS, Nakaya HI, Soltys DT, Menck CF, Reis EM, Verjovski-Almeida S.
PLoS Genet. 2013; 9(8):e1003705. Epub 2013 Aug 22. PMID: 23990798


Non-coding transcription characterization and annotation: a guide and web resource for non-coding RNA databases.
Paschoal AR, Maracaja-Coutinho V, Setubal JC, Simões ZL, Verjovski-Almeida S, Durham AM.
RNA Biol. 2012 Mar; 9(3):274-82. Review. PMID: 22336709


Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer.
Tahira AC, Kubrusly MS, Faria MF, Dazzani B, Fonseca RS, Maracaja-Coutinho V, Verjovski-Almeida S, Machado MC, Reis EM.
Mol Cancer. 2011 Nov 13; 10:141. PMID: 22078386


Long intronic noncoding RNA transcription: expression noise or expression choice?
Louro R, Smirnova AS, Verjovski-Almeida S.
Genomics. 2009 Apr; 93(4):291-8. Review. PMID: 19071207


Gene expression profiling reveals molecular marker candidates of laryngeal squamous cell carcinoma.
Colombo J, Fachel AA, De Freitas Calmon M, Cury PM, Fukuyama EE, Tajara EH, Cordeiro JA, Verjovski-Almeida S, Reis EM, Rahal P.
Oncol Rep. 2009 Mar; 21(3):649-63. PMID: 19212623


Identification of protein-coding and intronic noncoding RNAs down-regulated in clear cell renal carcinoma.
Brito GC, Fachel AA, Vettore AL, Vignal GM, Gimba ER, Campos FS, Barcinski MA, Verjovski-Almeida S, Reis EM.
Mol Carcinog. 2008 Oct; 47(10):757-67. PMID: 18348187


Splice variants of TLE family genes and up-regulation of a TLE3 isoform in prostate tumors.
Nakaya HI, Beckedorff FC, Baldini ML, Fachel AA, Reis EM, Verjovski-Almeida S.
Biochem Biophys Res Commun. 2007 Dec 28; 364(4):918-23. PMID: 18273443


Genome mapping and expression analyses of human intronic noncoding RNAs reveal tissue-specific patterns and enrichment in genes related to regulation of transcription.
Nakaya HI, Amaral PP, Louro R, Lopes A, Fachel AA, Moreira YB, El-Jundi TA, da Silva AM, Reis EM, Verjovski-Almeida S.
Genome Biol. 2007; 8(3):R43. PMID: 17386095


Androgen responsive intronic non-coding RNAs.
Louro R, Nakaya HI, Amaral PP, Festa F, Sogayar MC, da Silva AM, Verjovski-Almeida S, Reis EM.
BMC Biol. 2007 Jan 30; 5:4. PMID: 17263875


Evaluation of reference-based two-color methods for measurement of gene expression ratios using spotted cDNA microarrays.
Peixoto BR, Vêncio RZ, Egidio CM, Mota-Vieira L, Verjovski-Almeida S, Reis EM.
BMC Genomics. 2006 Feb 24; 7:35. PMID: 16504121


Gene expression arrays in cancer research: methods and applications.
Brentani RR, Carraro DM, Verjovski-Almeida S, Reis EM, Neves EJ, de Souza SJ, Carvalho AF, Brentani H, Reis LF.
Crit Rev Oncol Hematol. 2005 May; 54(2):95-105. Review. PMID: 15843092


As antisense RNA gets intronic.
Reis EM, Louro R, Nakaya HI, Verjovski-Almeida S.
OMICS. 2005 Spring; 9(1):2-12. Review. PMID: 15805775


Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer.
Reis EM, Nakaya HI, Louro R, Canavez FC, Flatschart AV, Almeida GT, Egidio CM, Paquola AC, Machado AA, Festa F, Yamamoto D, Alvarenga R, da Silva CC, Brito GC, Simon SD, Moreira-Filho CA, Leite KR, Camara-Lopes LH, Campos FS, Gimba E, Vignal GM, El-Dorry H, Sogayar MC, Barcinski MA, da Silva AM, Verjovski-Almeida S.
Oncogene. 2004 Aug 26; 23(39):6684-92. PMID: 15221013


More publications in Prof. Sergio Verjovski-Almeida's CV
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Key publications on Schistosoma mansoni gene expression

Interaction of an esophageal MEG protein from schistosomes with a human S100 protein involved in inflammatory response.
Orcia D, Zeraik AE, Lopes JL, Macedo JN, Santos CR, Oliveira KC, Anderson L, Wallace BA, Verjovski-Almeida S, Araujo AP, DeMarco R.
Biochim Biophys Acta. 2016 Sep 15. doi: 10.1016/j.bbagen.2016.09.015. PMID: 27639541


Human TNF-α induces differential protein phosphorylation in Schistosoma mansoni adult male worms.
Oliveira KC, Carvalho ML, Bonatto JM, Schechtman D, Verjovski-Almeida S.
Parasitol Res. 2016 Feb; 115(2):817-28. PMID: 26547565


Schistosoma mansoni Egg, Adult Male and Female Comparative Gene Expression Analysis and Identification of Novel Genes by RNA-Seq.
Anderson L, Amaral MS, Beckedorff F, Silva LF, Dazzani B, Oliveira KC, Almeida GT, Gomes MR, Pires DS, Setubal JC, DeMarco R, Verjovski-Almeida S.
PLoS Negl Trop Dis. 2015 Dec 31; 9(12):e0004334. PMID: 26719891


Synergy of Omeprazole and Praziquantel in vitro Treatment against Schistosoma mansoni Adult Worms.
Almeida GT, Lage RC, Anderson L, Venancio TM, Nakaya HI, Miyasato PA, Rofatto HK, Zerlotini A, Nakano E, Oliveira G, Verjovski-Almeida S.
PLoS Negl Trop Dis. 2015 Sep 24; 9(9):e0004086. PMID: 26402251


Exploring the Schistosoma mansoni adult male transcriptome using RNA-seq.
Almeida GT, Amaral MS, Beckedorff FC, Kitajima JP, DeMarco R, Verjovski-Almeida S.
Exp Parasitol. 2012 Sep; 132(1):22-31. PMID: 21745473


Effect of human TGF-β on the gene expression profile of Schistosoma mansoni adult worms.
Oliveira KC, Carvalho ML, Verjovski-Almeida S, LoVerde PT.
Mol Biochem Parasitol. 2012 Jun; 183(2):132-9. PMID: 22387759


Schistosoma mansoni histones: From transcription to chromatin regulation; an in silico analysis.
Anderson L, Pierce RJ, Verjovski-Almeida S.
Mol Biochem Parasitol. 2012 Jun; 183(2):105-14. Review. PMID: 22414701


Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts.
DeMarco R, Mathieson W, Manuel SJ, Dillon GP, Curwen RS, Ashton PD, Ivens AC, Berriman M, Verjovski-Almeida S, Wilson RA.
Genome Res. 2010 Aug; 20(8):1112-21. PMID: 20606017


Bursts of transposition from non-long terminal repeat retrotransposon families of the RTE clade in Schistosoma mansoni.
Venancio TM, Wilson RA, Verjovski-Almeida S, DeMarco R.
Int J Parasitol. 2010 May; 40(6):743-9. PMID: 20018191


Identification of the Schistosoma mansoni TNF-alpha receptor gene and the effect of human TNF-alpha on the parasite gene expression profile.
Oliveira KC, Carvalho ML, Venancio TM, Miyasato PA, Kawano T, DeMarco R, Verjovski-Almeida S.
PLoS Negl Trop Dis. 2009 Dec 1; 3(12):e556. PMID: 19956564


Analysis of Schistosoma mansoni genes shared with Deuterostomia and with possible roles in host interactions.
Venancio TM, DeMarco R, Almeida GT, Oliveira KC, Setubal JC, Verjovski-Almeida S.
BMC Genomics. 2007 Nov 8; 8:407. PMID: 17996068


A quantitative view of the transcriptome of Schistosoma mansoni adult-worms using SAGE.
Ojopi EP, Oliveira PS, Nunes DN, Paquola A, DeMarco R, Gregorio SP, Aires KA, Menck CF, Leite LC, Verjovski-Almeida S, Dias-Neto E.
BMC Genomics. 2007 Jun 21; 8:186. PMID: 17584941


Use of a 44k oligoarray to explore the transcriptome of Schistosoma mansoni adult worms.
Verjovski-Almeida S, Venancio TM, Oliveira KC, Almeida GT, DeMarco R.
Exp Parasitol. 2007 Nov; 117(3):236-45. PMID: 17517391


SmTRC1, a novel Schistosoma mansoni DNA transposon, discloses new families of animal and fungi transposons belonging to the CACTA superfamily.
DeMarco R, Venancio TM, Verjovski-Almeida S.
BMC Evol Biol. 2006 Nov 7; 6:89. PMID: 17090310


Gender biased differential alternative splicing patterns of the transcriptional cofactor CA150 gene in Schistosoma mansoni.
DeMarco R, Oliveira KC, Venancio TM, Verjovski-Almeida S.
Mol Biochem Parasitol. 2006 Dec; 150(2):123-31. PMID: 16904200


Identification of 18 new transcribed retrotransposons in Schistosoma mansoni.
DeMarco R, Machado AA, Bisson-Filho AW, Verjovski-Almeida S.
Biochem Biophys Res Commun. 2005 Jul 22; 333(1):230-40. PMID: 15939396


Schistosome transcriptome: insights and perspectives for functional genomics.
Verjovski-Almeida S, Leite LC, Dias-Neto E, Menck CF, Wilson RA.
Trends Parasitol. 2004 Jul; 20(7):304-8. Review. PMID: 15193558


Saci-1, -2, and -3 and Perere, four novel retrotransposons with high transcriptional activities from the human parasite Schistosoma mansoni.
DeMarco R, Kowaltowski AT, Machado AA, Soares MB, Gargioni C, Kawano T, Rodrigues V, Madeira AM, Wilson RA, Menck CF, Setubal JC, Dias-Neto E, Leite LC, Verjovski-Almeida S.
J Virol. 2004 Mar; 78(6):2967-78. Erratum in: J Virol. 2004 May; 78(9):4950. PMID: 14990715


Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni.
Verjovski-Almeida S, DeMarco R, Martins EA, Guimaraes PE, Ojopi EP, Paquola AC, Piazza JP, Nishiyama MY Jr, Kitajima JP, Adamson RE, Ashton PD, Bonaldo MF, Coulson PS, Dillon GP, Farias LP, Gregorio SP, Ho PL, Leite RA, Malaquias LC, Marques RC, Miyasato PA, Nascimento AL, Ohlweiler FP, Reis EM, Ribeiro MA, Sa RG, Stukart GC, Soares MB, Gargioni C, Kawano T, Rodrigues V, Madeira AM, Wilson RA, Menck CF, Setubal JC, Leite LC, Dias-Neto E.
Nat Genet. 2003 Oct; 35(2):148-57. PMID: 12973350


More publications in Prof. Sergio Verjovski-Almeida's CV
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Lab on the map

About São Paulo:

Founded: January 25, 1554
Area: 1,522.986 km²
Population: 11 037 593

Official website of the city
Official tourism site

Weather forecast
Buses and metrô

Wikipedia about São Paulo

Our bookmarks

In the section below we share our collection of the links that are used almost daily by researchers of our group.

Databases

UCSC Genome Browser
ArrayExpress Archive
SRA Database
The Human Protein Atlas
UniProt
GeneCards V3

JASPAR Database
RBPDB

Schistosoma mansoni
Genome Project



GO enrichment analysis

Metascape
Enrichr
AmiGO
DAVID
GATHER


Cell banks

ATCC
DSMZ
CLS
Rio de Janeiro Cell Bank


Tools for every day

Synergizer

Reverse Complement
RNAfold webserver
RNAz webserver
catRAPID

NEBcutter V2.0
Primer3
IDT OligoAnalyzer
BLOCK-iT™ RNAi Designer
Optimized CRISPR Design
Genome Engineering Tools
QUMA

CPC
CPAT
ORF Finder
HCpolya


NCBI tools

PubMed
BLAST
Primer-BLAST
AceView

List of all NCBI resources

Publishers

Nature Publishing Group
AAAS Science Journals
Oxford University Press
HighWire Press
CSHL Press
BioMed Central
Springer (Life Sciences)
Elsevier (Life Sciences)
PLoS


Other links

ISI web of knowledge
Google Scholar
CrossRef


Genome browser at USP iCloud

Schistosoma mansoni
Genome Browser