Rosaura Hernández Rivas


Cinvestav Researcher 3D

PhD Molecular Biology (1992), IBT, UNAM

Category in the SNI: Level II

Tel: +52 (55) 5061-3325
Fax: +52 (55) 5061-3938
rohernan@mail.cinvestav.mx

Academic preparation

PhD (Molecular biology)  UNAM Mexico 1992.
Master in Science (Molecular Biology). CINVESTAV-IPN (Mexico).
Degree in biology. UNAM  Mexico 1987.

Postdoctoral stays

Department of Experimental Pathology, CINVESTAV-IPN. In the laboratory of Dr Esther Orozco Orozco. (1993-1994).

Unit of Experimental Parasitology at the Pasteur Institute, Paris. In the laboratory of Dr. Artur Scherf (1884-1996)

Sabbatical stays

Biologie des Hote-Parasite Interactions, Institut Pasteur. Paris, France. In the laboratory of Dr. Artur Scherf (2005).

Biologie des Hote-Parasite Interactions, Institut Pasteur. Paris, France. In the laboratory of Dr. Artur Scherf (2011).

Research and teaching experience

  • Biomedical Research Institute. Molecular Biology ofApartment UACPYP CCH (From March to September 1992).
  • Department of Experimental Pathology, CINVESTAV-IPN (March 1993).
  • Department of Molecular Biomedicine, CINVESTAV-IPN from November 1996 to date).
  • Role of chromatin in the differential expression of genes in Plasmodium falciparum.

  • Study of nuclear architecture in Plasmodium and its involvement in the expression of virulence genes.

  • Characterization and study of non-coding RNA of the parasite and its involvement in the formation of heterochromatin.

  • Epigenetic mechanisms implicated in the encystment of E. invadens

Collaborations

  • Dr. Artur Scherf. Institut Pasteur. Unité des Interaction Hote-Parasite. Paris Francia.
  • Dr. Kirk Deitsch. Department of Microbiology and Immunology. Weill Medical College. Cornell University. NY. U.S.A.
  • Dr. Félix Recillas Targa, Instituto de Fisiología Celular. Universidad Nacional Autónoma de México. México, D. F.
  • Dra. Nancy Guillén Instituto Pasteur, Unité des Interaction Hote-Parasite. Paris Francia.
  • Dr. Santiago Martinez Calvillo. Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México.
  • Dr. Goldberg Daniel. Professor of Medicine and of Molecular Microbiology at Washington University in St. Louis School of Medicine.

Area of expertise: Molecular Biology

Publications

International Publications: 41
National Publications: 7
International chapters book: 3
National chapters book: 4
Graduated Students
Doctor of Philosopy Science: 4
Master in Science: 22
B.S: 2

Congress: 76

Honours and Awards

  • Gabino Barreda Medal 1992 PhD from the National Autonomous University of Mexico.
  • 1992 Honorable Mention in the doctoral degree examination. National Autonomous University of Mexico
  • 1993 Award, Lola and Igo Flisser for the best doctoral thesis in Parasitology.
  • 1994 Scholarship, Foundation pour la Recherche Médicale.
  • 1995 Scholarship, Pasteur-Weizmann.
  • 1996 Scholarship, Foundation pour la Recherche Médicale.
  • 2006 Award, Lola and Igo Flisser for the best doctoral thesis in Parasitology my PhD student Omar Khayyam Ruvalcaba.
  • 2006 Honorable Mention, Lola and Igo Flisser Award for the best doctoral thesis in Parasitology my PhD student Dvorak Montiel County.

Funding

International

  1. European Union for research and technical development (1999-2002) "Adhesion of Plasmodium falciparum -infected erythrocytes to host glycosaminoglycans and de- sequestration studies in Saimiri monkeys" . Durantes three years from March 9, 1998.
  2. Mexico - France Bilateral Project ANR- CONACyT " Paractin : Impact of actin and actin related proteins in human parasitic infections" . From July 2011 to July 2014. Amount $ 3,069,372.29

National

  1. México CONACyT (1998-2000) " Molecular and Cellular Study var -CSA gene of Plasmodium falciparum and its relationship with Maternal Malaria ".
  2. CONACyT ( Mexico ) ( 2001-2004 ) " Isolation and characterization of var gene promoter -CSA of Plasmodium falciparum ".
  3. CONACyT ( México ) ( 2005 to January 30, 2008 ) . Identification and characterization of the binding region of PfTBP two Plasmodium falciparum genes and identification of partial TBP associated factors ( TAFs ).
  4. CONACyT ( México ) ( June 2008 to June 2011 ) . Identification of nuclear factors that interact with Rep20 subtelomeric region in Plasmodium falciparum".
  5. CONACyT ( México ) January 2013 to January 2016 . " Processing the amino terminus of histone H3 in P. falciparum : Probable epigenetic mechanism ".

Work description

Plasmodium falciparum, a protozoan that is the causal agent of the most severe form of human malaria, has a complex life cycle within two different hosts: the Anopheles mosquito and humans. In order to complete its life cycle, P. falciparum invades different types of cells and self-propagates in very distinct environments in the mosquito (gut, hemolymph and salivary glands) as well as in the human host (liver and erythrocytes). Each of these distinct environments exerts selective pressure related to morphological changes and forces Plasmodium to exhibit differential gene expression during its life cycle.  Therefore our primary research interests are centred on the study of transcriptional gene regulation in P. falciparum at three different levels: 1) chromatin structure, 2) nuclear architecture, and 3) non-coding RNA.

All this knowledge has been generated by using novel techniques such as:

  • Chromatin immunoprecipitation (DNA-ChIP)
  • EMSA assays of DNA and RNA
  • Northwestern and Southwestern
  • RNA / DNA oligonucleotide pulldown
  • In situ hybridization assays by using DNA or RNA probes (FISH -RNA/DNA)
  • Nuclear Run-on Assays

Recent results

Telomeres are not just the physical end of linear chromosomes, they exert essential functions, for example, in genome integrity and cell division. One relevant aspect is that telomeres recruit specific molecules that create a chromatin environment that represses gene activity in a distance-dependent manner. This effect is also called the telomere position effect (TPE). In Plasmodium several genes implicated in virulence such as the var genes are located adjacent to subtelomeric regions. Recently, data have also begun to emerge in our lab about a possible role for   non-coding RNA (lncRNA) from telomeres and subtelomeric regions in Plasmodium gene regulation. In higher eukaryotes ncRNAs have well-established roles in the assembly of heterochromatin via RNA interference (RNAi), but this is a controversial subject for Plasmodium since the genus does not possess a functional RNAi system.  Therefore, we propose that these ncRNAs may be involved in telomeric silencing by a mechanism different from RNAi.

Additionally we have identified that the histone H3 clipping regulate gene expression of genes implicated in the replication of  this parasite and that controlled H3  histone proteolysis may be part of a mechanism for introducing variation into the chromatin polymer.

Representative publications

  1. Hernández-Rivas R, Herrera-Solorio AM, Sierra-Miranda M, Delgadillo DM, Vargas M.  Impact of chromosome ends on the biology and virulence of Plasmodium falciparum. Mol Biochem Parasitol. 2013 Feb;187(2):121-8.

  2. Sierra-Miranda M, Delgadillo DM, Mancio-Silva L, Vargas M, Villegas-Sepulveda N, Martínez-Calvillo S, Scherf A, Hernandez-Rivas R..Two long non-coding RNAs generated from subtelomeric regions accumulate in a novel perinuclear compartment in Plasmodium falciparum. Mol Biochem Parasitol. 2012 Sep;185(1):36-47.

  3. Chêne A, Vembar SS, Rivière L, Lopez-Rubio JJ, Claes A, Siegel TN, Sakamoto H, Scheidig-Benatar C, Hernandez-Rivas R, Scherf A. PfAlbas constitute a new eukaryotic DNA/RNA-binding protein family in malaria parasites. Nucleic Acids Res. 2012 Apr;40(7):3066-77.

  4. Hernández-Rivas R, Pérez-Toledo K, Herrera Solorio AM, Delgadillo DM, Vargas M. Telomeric heterochromatin in Plasmodium falciparum. J Biomed Biotechnol.2010;2010:29050

  5. Pérez-Toledo K, Rojas-Meza AP, Mancio-Silva L, Hernández-Cuevas NA, DelgadilloDM, Vargas M, Martínez-Calvillo S, Scherf A, Hernandez-Rivas R. Plasmodiumfalciparum heterochromatin protein 1 binds to tri-methylated histone 3 lysine 9and is linked to mutually exclusive expression of var genes. Nucleic Acids Res.2009 May; 37(8):2596-606.

  6. Mancio-Silva L, Rojas-Meza AP, Vargas M, Scherf A, Hernandez-Rivas R.
    Differential association of Orc1 and Sir2 proteins to telomeric domains in Plasmodium falciparum. J. Cell Sci. 2008 Jun 15; 121(Pt 12):2046-53.

  7. Lopez-Rubio JJ, Gontijo AM, Nunes MC, Issar N, Hernandez Rivas R, Scherf A.5' flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites.
    Mol Microbiol. 2007 Dec; 66(6):1296-305. Epub 2007 Nov 19.

  8. Lucio Freitas-Junior*, Rosaura Hernández-Rivas*, Stuart A. Ralph, Dvorak Montiel-Condado, Omar K. Ruvalcaba Salazar, Ana Paola Rojas-Meza, Lilia Mancio-Silvas and Artur Scherf. (2005) Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in Malaria parasites.Cell. 2005 Apr 8;121(1):25-36.

* These authors contributed equally to this work

Shaded publications have been highlighted by he journal by a special comment (Preview o Commentary)

Biochem Parasitol. 2005 Apr;140(2):183-96

Dulce Maria Delgadillo . Research Assistant

  • José Miguel Miranda Sierra .PhD  Student
  • Adriana Contreras Quiroz . PhD Student
  • Gabriela Meza Romero. PhD Student
  • José Eduardo Perez Mojica . Master Student
  • Daniela Lozano Beloved. Master Student

The ncRNAs define a novel subdomain in the P. falciparum nucleus. (A) RNA-FISH signals are shown in red, and DNA-FISH signals are shown in green (TARE-6). The signals of the TARE-6 ncRNA and telomeric DNA do not co-localize in ring stages, but in the late-schizont stage some telomere clusters are transcribed and co-localize with TARE-6 ncRNA probe. (B) P. falciparum nucleus present a complex nuclear architecture with several subcompartments localized in the nuclear periphery as are: telomeric clusters, var gene expression site, nucleolus and non-coding RNA compartment. (C) RNA-FISH signals are shown in red (TARE-6), and 28S rDNA DNA-FISH signals are ingreen. The signals from 28S rDNA and the non-coding TARE-6 transcript do not co-localize. (D) Two-color RNA-FISH of a var2CSA RNA probe (green) and TARE-6 ss ncRNA transcripts (red) for ring stage parasites (FCR3-CSA parasite population). The signals from the var2CSA transcripts and the TARE-6 ncRNAs do not co-localize. In all images, nuclear DNA was stained with DAPI (blue). Scale bars: 1 _m for the ring and schizont stages. 70 nuclei were analyzed from two independent experiments.