Research papers by Diego Diez
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    WELCOME

    I am a postdoctoral researcher in Professor Kanehisa's laboratory, at Bioinformatics Center (Kyoto University). My background is Biochemistry, Molecular Biology and Bioinformatics. I am interested in genome evolution, regulatory networks and complex systems.

    My research is centered on pathological aspects of inflammation, in particular to the role of inflammation in asthma and atherosclerosis. I am interested on the integration of experimental data with systems biology methods (i.e. network analysis) to obtain a better understanding on the pathways driving disease onset and progression. My current work has been centered on integration of protein-protein interactions (PPI) and gene expression data.

    I continue contributing to the varDB project, where my interests are centered on the evolutionary aspects of antigenic variations in different pathogenic organisms.

    I got my PhD working with Professor Juan Bernal at the Instituto de Investigaciones Biomedicas (CSIC/UAM). My research centered on understanding the transcriptional aspects of thyroid hormone action in the brain.

    Until August 2009 I had a fellowship of the Japanese Society of the Promotion of Science (JSPS) program (long term postdoctoral research fellowship), to whom I am very grateful.

    My (extended) resume.

    Diego.

    RESEARCH

    Network analysis of inflammation

    Atherosclerosis is a complex disease with many factors involved. It is also the main cause of cardiovascular disease and stroke, the first cause of death on industrilized societies. Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symtoms, airway obstruction and bronchospasm.

    In this project I am interesting on the reconstruction of regulatory networks driving disease onset and progression. To this aim I apply a number of systems biology and bioinformatics approaches, and integrate patient's derivide expression data with existing knowledge about protein-protein interactions.

    varDB: a database of antigenic variant gene sequences

    Pathogens from very different taxonomic origins like viruses, bacteria and fungi, use antigenic variation as a way to generate epitope diversity. The mechanisms involved are various but shared in some cases. The varDB project aims to be a central repository for antigenic variant gene families that may provided a way for cross-species studies. Therefore, a method to automacally retrieved sequences from the original repositories, and classifiy them into gene families is being developed.

    These sequences will be used to identify sets of shared regulatory motifs that may be hidden in the sequences of many pathogens, irrespective thir phylogenetic origin.

    Evolution of the Ras switch in eukaryotes

    The Ras switch is a regulatory module fundamental in many biological processes like cell proliferation and differentiation. Ras proteins are small guanine nucleotide binding proteins that alternate between a GDP-bound, inactive state and a GTP-bound active state. Two protein families regulate the activity of Ras proteins: Guanine nucleotiotide exchange factors (GEF) and GTPase activator proteins (GAP).

    We analyzed the repertorie of Ras proteins and its regulators among several eukaryote organisms, including yeast, worm, insect, fish, birds and mammals. The results we describe are important to understand how complex regulatory networks, like the Ras switch, evolve from a set of limited paralogues sequences.

    Thyroid hormone action in the brain

    The effects of thyroid hormone (TH) in the brain are well studied in the postnatal period. However, the role of TH in the fetal and adult brain is less understood. TH exert most of their functions through the binding to nuclear receptors that act as transcription factors modulating the expression of target genes.

    At Juan Bernal's laboratory we studied the roles of TH in both the developing and adult brain. A transcriptomic approach was used to identify genes sensitive to TH under different experimental paradigms. Validation of the candidate genes is done using RT-PCR. We found evidence of a role of TH in homeostasis of the adult and fetal brain.

    Codelink: an R package for analysis of GE healthcare gene expression bioarrays

    This Bioconductor package provides basic functionality to help in the analysis of Codelink™ arrays. Codelink™ is a microarray platform for assessing gene expression using short (30mer) oligonucleotide probes.

    The codelink package has functions for reading, analyzing and assessing quality of microarray data. Further information can be found in the package vignette.
    [Package home page]

    I have supervised/helped in the development of other R packages, most of them submitted to Bioconductor:

    GeneRegionScan: A package designed to help in the analysis of specific genes obtained from Affymetrix experiments, but using prove-level information. This kind of approach enables the study of alternative splicing events, and the association between genotypic differences (SNPs) and changes in expression levels.
    [Package home page]

    Agi4x44PreProcess: A package designed to help in the analysis of Agilent 4x44 microarray platform.
    [Package home page]

     

    PUBLICATIONS
    1. Diez D, Sanchez-Jimenez F, and Ranea JA, Evolutionary expansion of the Ras switch regulatory module in eukaryotes. Nucleic Acids Res, 2011. 39(13): p. 5526-37.
      [pubmed] [preprint]
    2. Grijota-Martinez C, Diez D, Morreale de Escobar G, Bernal J, and Morte B, Lack of action of exogenously administered t3 on the fetal rat brain despite expression of the monocarboxylate transporter 8. Endocrinology, 2011. 152(4): p. 1713-21.
      [pubmed] [preprint]
    3. Kirwan G, Diez D, Haeggström J, Goto S, and Wheelock C, Systems Biology Approaches for Investigating the Relationship Between Lipids and Cardiovascular Disease. Current Cardiovascular Risk Reports, 2011. 5(1): p. 52-61.
      [pubmed] [preprint]
    4. Morte B, Ceballos A, Diez D, Grijota-Martinez C, Dumitrescu AM, Di Cosmo C, Galton VA, Refetoff S, and Bernal J, Thyroid hormone-regulated mouse cerebral cortex genes are differentially dependent on the source of the hormone: a study in monocarboxylate transporter-8- and deiodinase-2-deficient mice. Endocrinology, 2010. 151(5): p. 2381-7.
      [pubmed] [preprint]
    5. Morte B, Diez D, Auso E, Belinchon MM, Gil-Ibanez P, Grijota-Martinez C, Navarro D, Morreale de Escobar G, Berbel P, and Bernal J, Thyroid Hormone Regulation of Gene Expression in the Developing RatFetal Cerebral Cortex: Prominent Role of the Ca2+/Calmodulin-Dependent Protein Kinase IV Pathway. Endocrinology, 2010. 151(2): p. 810-820.
      [pubmed] [preprint]
    6. Hayes CN, Diez D, Joannin N, Kanehisa M, Wahlgren M, Wheelock CE, and Goto S, Tools for investigating mechanisms of antigenic variation: new extensions to varDB. Genome Inform, 2009. 23(1): p. 46-59.
      [pubmed] [preprint]
    7. Diez D, Wheelock AM, Goto S, Haeggstrom JZ, Paulsson-Berne G, Hansson GK, Hedin U, Gabrielsen A, and Wheelock CE, The use of network analyses for elucidating mechanisms in cardiovascular disease. Mol Biosyst, 2010. 6(2): p. 289-304.
      [pubmed] [preprint]
    8. Diez D, Hayes N, Joannin N, Normark J, Kanehisa M, Wahlgren M, Wheelock CE, and Goto S, varDB: a database of antigenic variant sequences- current status and future prospects. Acta Trop, 2009. In press.
      [pubmed] [preprint]
    9. Folkersen L, Diez D, Wheelock CE, Haeggstrom JZ, Goto S, Eriksson P, and Gabrielsen A, GeneRegionScan: a Bioconductor package for probe-level analysis of specific, small regions of the genome. Bioinformatics, 2009. 25(15): p. 1978-9.
      [pubmed] [preprint]
    10. Wheelock CE, Wheelock AM, Kawashima S, Diez D, Kanehisa M, van Erk M, Kleemann R, Haeggstrom JZ, and Goto S, Systems biology approaches and pathway tools for investigating cardiovascular disease. Mol Biosyst, 2009. 5(6): p. 588-602.
      [pubmed] [preprint]
    11. Hayes CN, Diez D, Joannin N, Honda W, Kanehisa M, Wahlgren M, Wheelock CE, and Goto S, varDB: a pathogen-specific sequence database of protein families involved in antigenic variation. Bioinformatics, 2008. 24(21): p. 2564-5.
      [pubmed] [preprint]
    12. Diez D, Grijota-Martinez C, Agretti P, De Marco G, Tonacchera M, Pinchera A, de Escobar GM, Bernal J, and Morte B, Thyroid hormone action in the adult brain: gene expression profiling of the effects of single and multiple doses of triiodo-L-thyronine in the rat striatum. Endocrinology, 2008. 149(8): p. 3989-4000.
      [pubmed] [preprint]
    13. Diez D, Alvarez R, and Dopazo A, Codelink: an R package for analysis of GE healthcare gene expression bioarrays. Bioinformatics, 2007. 23(9): p. 1168-9.
      [pubmed] [preprint]