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Molecular genetics of mammalian microRNAs
- Roles of miRNAs in stem cells and cancer
- microRNA regulatory networks (targetomics)
- Identification of disease genes regulated by microRNAs
The fundamental aim of our research is to define the roles of mammalian microRNAs (miRNAs) in normal physiology and disease. To achieve this goal,
we combine the classical methods of mouse genetics and cell/molecular biology with modern genomics, and bioinformatics
technologies. Our analysis of the first mouse germline miRNA knockout, miR-155, revealed an essential
role for this miRNA in humoral immunity and B and T lymphocyte differentiation. This work established that
individual miRNAs are of key importance in mammals. We are studying the functional roles of other phylogenetically
conserved miRNAs, including let-7 and miR-99/100 using targeted gene knockout embryonic stem cells (ES) and mice.
A second long term goal of our lab is to discover the circuitry or network of posttranscriptional gene
silencing by mammalian miRNAs. For example, we identified Pu.1 and c-Maf as direct targets of miR-155
in B and T cells respectively by microarray analysis. As a corollary to this line of inquiry, we expect to more
generally discover the key circuitry or ‘targetomes’ of additional miRNAs in diverse tissues/cells.
We hope that our research will eventually lead to increased understanding on the impact of miRNAs on global
gene expression and human disease.
Selected Publications
Rodriguez A, Zhou Z, Tang ML, Meller S, Chen J, Bellen H, Kimbrell DA (1996) Identification of immune system and response genes, and novel
mutations causing melanotic tumor formation in Drosophila melanogaster. Genetics 143:929-940.
Rodriguez A, Oliver H, Zou H, Chen P, Wang X, Abrams JM (1999) Dark is a Drosophila homologue of Apaf-1/CED-4 and functions in an evolutionarily
conserved death pathway. Nature Cell Biology 1:272-279.
Leulier F, Rodriguez A, Khush RS, Abrams JM, Lemaitre B (2000) The Drosophila caspase Dredd is required to resist Gram-negative bacterial infection.
EMBO Reports 1:353-358.
Rodriguez A, Chen P, Oliver H, Abrams JM (2002) Unrestrained caspase-dependent cell death caused by loss of Diap1 function requires the Drosophila
Apaf-1 homolog, Dark. EMBO Journal 21:2189-2197.
Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Research
14:1902-1910.
Chew SK, Akdemir F, Chen P, Lu WJ, Mills K, Daish T, Kumar S, Rodriguez A, Abrams JM (2004) The apical caspase dronc governs programmed and unprogrammed cell
death in Drosophila. Developmental Cell 7:897-907.
Akdemir F, Farkas R, Chen P, Juhasz G, Medved'ová L, Sass M, Wang L, Wang X, Chittaranjan S, Gorski SM, Rodriguez A, Abrams JM (2006) Autophagy occurs
upstream or parallel to the apoptosome during histolytic cell death. Development 133:1457-1465.
Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M,
Bradley A (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316:608-611.
Vigorito E, Perks KL, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S, Das PP, Miska EA, Rodriguez A, Bradley A, Smith KG, Rada C, Enright AJ, Toellner KM,
Maclennan IC, Turner M (2007) microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 27:847-859.
Contact Information
- Antony Rodriguez, Ph.D.
- Department of Human and Molecular Genetics
- Baylor College of Medicine
- One Baylor Plaza
- Margaret Alkek Research Building, R806
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-1980
- Fax:
- E-mail: antonyr@bcm.tmc.edu
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