Michael E. Fant, M.D., Ph.D.
1980, Vanderbilt University
UT-Houston Medical School
Pediatrics
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Michael E. Fant, M.D., Ph.D. 1980, Vanderbilt University UT-Houston Medical School |
Research Interests: Cellular mechanisms regulating placental development; mesenchymal-trophoblast signaling interactions important in placental growth and function; peptide growth factors regulating placental growth; trophoblast-specific genes in placental development
Fetal development is dependent upon normal placental growth and function. The cellular and molecular processes regulating placental growth have not been fully characterized. However, a number of placenta-specific genes have been identified that appear to be essential to normal placental development. My laboratory is currently studying the role of Plac1, a novel X-linked and placenta-specific gene, in placental development. Nothing is known regarding the function of Plac1. However, it maps to an area of the X chromosome thought to be important in placental and fetal development. Furthermore, it shares sequence homology with the zona pellucida protein 3 (an oocyte cell-surface glycoprotein essential for normal sperm-egg interactions), suggesting that Plac1 acts as an extracellular receptor-like protein to facilitate interactions (with other cells or regulatory molecules) unique to the maternal-fetal interface. Plac1 is expressed exclusively in cells of trophoblastic lineage in the mouse placenta with expression highest in early gestation and diminishing significantly by day 14.5 when mouse placental development is complete. We have similarly shown that Plac1 is limited to the trophoblast in the human. By contrast, however, human Plac1 is strongly expressed throughout gestation.
We are using a variety of approaches to define the precise role of Plac1. First, we are developing a Plac1-null mouse mutant model to confirm its importance to placental development and defining the expression pattern of the Plac1 polypeptide. Second, we are using over-expressio and gene "knock-down" approaches to study its function at the cellular level. Third, we are studying Plac1 gene regulation by peptide growth factors known to be relevant to placental growth. Finally, we will use conventional biochemical and molecular techniques to identify potential interacting peptides for Plac1. The specific focus of the student will depend on their background and interests.
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Fant M, Weisoly DL, Cocchia M, Huber R, Khan S, Lunt T, Schlessinger D (2002) Plac1, a trophoblast-specific gene, is expressed throughout pregnancy in the human placenta and modulated by keratinocyte growth factir (KGF). Molecular Reproduction and Development (in press)
Khan S, Blackburn M, Mao D-L, Huber R, Schlessinger D, Fant ME (2001) Glypican-3 (GPC3) expression in human placenta: localization to the differentiated syncytiotrophoblast. Histology and Histopathology 16:71-78.
Fang J, Furesz T, Smith Ch, Fant ME (1999) IGF binding protein-1 (IGFBP-1) is preferentially associated with the fetal-facing basal surface of the syncytiotrophoblast in the human placenta. Growth Hormone and IGF Research 9:438-444.
Fang, J Furesz T, Laurent R, Smith CH, Fant ME (1997) Spatial polarization of IGF receptors on the syncytiotrophoblast cell membrane. Pediatric Research 41:258-265.