Guillermo Oliver, Ph.D.
Department of Genetics and Tumor
St. Jude Children's Research Hospital
Department of Anatomy and Neurobiology
St. Jude Children's Research Hospital
MS 331, Room 3055
332 N. Lauderdale
Memphis, TN 38105
Phone: (901) 495-2697
Fax: (901) 495-2907
Email: Guillermo Oliver
- Ph.D. Institution: University of Uruguay, Montevideo, Uruguay
The general goal of my research program is to understand the cellular and molecular mechanisms controlling mammalian organ development in health and disease by focusing in two homedomain-containing transcription factors (Six3 and Prox1). During the last few years, we generated a number of valuable animal models that have been critical in the progress of our research. The detailed characterization of many of these animal models highlighted the important roles of these two genes in mammalian embryonic development and disease. We gathered valuable information about how these genes control basic aspects of brain, visual system and lymphatic development and generated a number of animal models of disease aimed to better understand the role of these genes in a variety of human disorders.
The detailed characterization of generated Six3 standard and conditional knock-out mouse strains revealed the critical function of this gene during brain formation and regionalization as we previously demonstrated that Six3 directly represses Wnt1 expression in the anterior neuroectoderm and that this step is essential for forebrain development. Using a generated Six3 conditional mouse strain we also determined that conditional deletion of Six3 in the presumptive lens ectoderm affected lens induction and specification positioning Six3 at the top of the regulatory pathway leading to lens formation. Using a similar conditional deletion approach we identified Six3 as the first gene whose activity is required to initiate neuroretina specification.
In relationship with Prox1, our previous work revealed that in mammals, Prox1 activity is critical for the development of many organs and tissues, such as lymphatic vasculature, dentate gyrus, lens, retina, and heart. Our initial work identified Prox1 as the first specific marker for lymphatic endothelial cells (LECs) and described the first mouse model devoid of a lymphatic vasculature. Subsequently, we demonstrated that blood endothelial cells (BECs) are the default condition from which a LEC fate is induced by Prox1. In a surprising twist, we also demonstrated that a defective lymphatic vasculature promotes late-onset obesity in Prox1 heterozygous mice, a result that could have important implications in public health. Later by using a lineage tracing approach, we showed that in mammals the lymphatic vasculature is exclusively venous derived, an issue that has been debated for over a century. More recently, we demonstrated that the LEC phenotype is plastic and requires constant expression of Prox1 to maintain its differentiated state.
- Yang Y, GarcĂa-Verdugo JM, Soriano-Navarro M, Srinivasan RS, Scallan JP, Singh MK, Epstein JA, Oliver G. Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos. Blood. 2012 Sep 13;120(11):2340-8. doi: 10.1182/blood-2012-05-428607. Epub 2012 Aug 2. PubMed PMID: 22859612; PubMed Central PMCID: PMC3447786.
- Lavado A, Oliver G. Six3 is required for ependymal cell maturation. Development. 2011 Dec;138(24):5291-300. doi: 10.1242/dev.067470. Epub 2011 Nov 9. PubMed PMID: 22071110; PubMed Central PMCID: PMC3222208.
- Srinivasan RS, Oliver G. Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves. Genes Dev. 2011 Oct 15;25(20):2187-97. doi: 10.1101/gad.16974811. PubMed PMID: 22012621; PubMed Central PMCID: PMC3205588.
- Liu W, Lagutin O, Swindell E, Jamrich M, Oliver G. Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate. J Clin Invest. 2010 Oct;120(10):3568-77. doi: 10.1172/JCI43219. Epub 2010 Sep 20. PubMed PMID: 20890044; PubMed Central PMCID: PMC2947236.
- Wang Y, Oliver G. Current views on the function of the lymphatic vasculature in health and disease. Genes Dev. 2010 Oct 1;24(19):2115-26. doi: 10.1101/gad.1955910. Review. PubMed PMID: 20889712; PubMed Central PMCID: PMC2947764.
- Lavado A, Lagutin OV, Chow LM, Baker SJ, Oliver G. Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis. PLoS Biol. 2010 Aug 17;8(8). doi:pii: e1000460. 10.1371/journal.pbio.1000460. PubMed PMID: 20808958; PubMed Central PMCID: PMC2923090.