BIOL240B Genetics Research Interests: A. Molecular and Cell Biology of Proliferative Vitreoretinopathy Proliferative vitreoretinopathy (PVR) is an ophthalmological condition in which the retinal pigment epithelium (RPE) cells break free from their monolayer in the posterior retina and migrate into the vitreous chamber. This results in an estimated 10% of patients who suffer from retinal detachments with retinal tears. During PVR, the RPE undergoes an epithelial mesenchymal transformation (EMT) as the intercellular adherens and tight junctions break down between cells. Epithelial and endothelial cells are joined to one another through a junctional complex that includes an adherens junction and an occludens or tight junction. Recent studies from other labs has shown that the loss of cell adhesion during EMT is, in part, under the control of the Notch pathway and that loss of tight junction expression is regulated by the zinc finger repressor Snail, which downregulates the expression of the tight junction molecules occludin and claudin as well as the adhesion molecule E-cadherin. My lab examines the possible role of the Snail family of transcription factors (Snail and Slug) in the EMT associated with PVR using a pig RPE cell model. Using a combination of molecular and cell biological techniques, we are examining the expression levels of adherens and tight junction molecules following exposure of RPE to freshly isolated vitreous. Specifically, the roles of the Snail family of transcription repressors will be studied. A number of undergraduate research assistants will work on different aspects of this project which will serve as a learning and research training experience for them. Data gathered during the scope of this work will help to broaden the ophthalmological community's understanding of the molecular triggers that bring about the phenotypic changes observed during PVR. B. Role of CD46 in the Retinal Pigment Epithelium Most recently, I have begun work to study the role of a molecule called CD46 and its role in the retinal pigment epithelium. Preliminary data from the McLaughlin lab at the University of Louisville suggests that the complement system may play a significant role in one of the leading diseases causing blindness in the elderly population, age-related macular degeneration. This study looks at a novel role in the retina for a regulatory protein in the complement system, CD46. Using a porcine cell culture model for retinal pigment epithelium, I plan to study this complement regulatory protein, which protects host cells from autologous complement attack, and its interactions with an adhesion molecule, beta1 integrin, to determine whether it plays a role in RPE adhesion to its basement membrane and Bruch's membrane.
Education: Postdoctoral Research Fellow, 1999-2001 Ph.D., Anatomical Sciences and Neurobiology, December 1998 B.S., Biology, May 1992 Grants and Funding: Collaborator, "QSAR of Adrenergic Receptor Antagonists", KY-IDEA Networks of Biomedical Research Excellence (KY-INBRE) through the National Institutes of Health. (2004-2008) "The Outer Blood Retinal Barrier in Xenopus laevis", Kentucky Biomedical Research Infrastructure Network/National Institutes of Health. (2002-2003) "Role of the PDZ3-SH3-GuK cluster of ZO-2 in tight junction function and regulation", Kentucky Biomedical Research Infrastructure Network/National Institutes of Health. (Summer, 2002) "Acquisition of transmission electron microscopy equipment for invertebrate and vertebrate pigment cell studies, undergraduate laboratory demonstrations, and undergraduate research", Co-PI, National Science Foundation. (2001-2003) "Regulation of the Outer Blood-Retinal Barrier." National Eye Institute, Public Health Service. (1999-2002) "Regulation of Outer Blood-Retinal Barrier by RPE Tight Junctions." Fight for Sight, the Research Division of Prevent Blindness America. (1999-2000) "Migratory responses of retinal pigment epithelium to different extracellular matrix environments." Sigma Xi, The Scientific Research Society. (1996-1997) "Apical membrane protein expression during postnatal development in the retinal pigment epithelium of normal and dystrophic rats." Sigma Xi, The Scientific Research Society. (1995-1996) DNA Sequences to NCBI: Lambert, R.C. and S.D. Wilt (2006). Ursus maritimus claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ901557. Lambert, R.C. and S.D. Wilt (2006). Phacochoerus africanus claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ901556. Lambert, R.C. and S.D. Wilt (2006). Halichoerus grypus claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ901555. Lambert, R.C. and S.D. Wilt (2006). Gorilla gorilla gorilla claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ887092. Lambert, R.C. and S.D. Wilt (2006). Alces alces claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ887091. Wilt, S.D. and K.S. Cashman (2005). Lemur macaco claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ248201. Wilt, S.D. and K.S. Cashman (2005). Cercopithecus aethiops claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ248200. Wilt, S.D. and K.S. Cashman (2005). Macaca assamensis claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ248199. Miller, K.S. and S.D. Wilt (2005). Ceratotherium simum simum claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ248198. Wilt, S.D. and C.W. Shepherd (2005). African elephant claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ185521. Wilt, S.D. and C.W. Shepherd (2005). Asian elephant claudin-1 gene, partial cds. National Center for Biotechnology Information, accession Shepherd, C.W., Miller, K.S. and S.D. Wilt. (2005) Orangutan claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ173242. Shepherd, C.W., Miller, K.S. and S.D. Wilt. (2005) Woolly monkey claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ173241. Miller, K.S., Shepherd, C.W. and S.D. Wilt. (2005) Gazelle claudin-1 gene, partial cds. National Center for Biotechnology Information, accession number DQ173240. Howard, J.M. and S.D. Wilt. (2004) Sus scrofa claudin-3 (CLDN3), partial cds. National Center for Biotechnology Information, accession number AY625258. Publications: Kiser, P.J., Liu, Z., Wilt, S.D. and G.D. Mower (in press) Changes in cellular and laminar expression of Dab-1 during the postnatal critical period in cat visual vortex and the effects of dark rearing. Brain Res. Wilt, S.D. (2004) Model organism: Xenopus laevis. In: Encyclopedia of Genetics, Revised edition. B.D. Ness, ed. Salem Press, Pasadena. 542-544. Wilt, S.D. and L.J. Rizzolo. (2001) Unique aspects of the blood brain barrier. In: Tight Junctions, J. M. Anderson and M. Cerejido, eds. CRC Press, Boca Raton. 415-433. Ban, Y., Wilt, S.D. and L.J. Rizzolo (2000) Two secreted retinal factors regulate different stages of development of the outer blood-retinal barrier. Brain Res. Dev. Brain Res.119: 259-67. Wilt, S.D., Greaton, C.J., Lutz, D.A., and B.J. McLaughlin. (1999) Mannose receptor is expressed in normal and dystrophic retinal pigment epithelium. Exp. Eye Res. 69: 405-411. Wilt, S.D. and B.J. McLaughlin. (1999) Is another mannose receptor-like lectin present in the retinal pigment epithelium? Curr. Eye Res.19: 1-3. Seligson, D. and S.D. Wilt. The history of mini-external fixation. In: Minifixation: mini-external fixation of the hand, foot, and wrist. E. Cziffer, ed. Literatura Medica, LTD, Hungary, 1994. Sponsored Student Presentations: Todd, Patricia and S.D. Wilt. (2008) An investigation of the mechanism for epithelial mesenchymal transformation in retinal pigment epithelium. Butler University Undergraduate Research Conference, Indianapolis, Indiana. Vaughn, K. and S.D. Wilt (2008) Do CD46, beta-1 integrin and discs large play a functional role in retinal pigment epithelium detachment? Butler University Undergraduate Research Conference, Indianapolis, Indiana and Bellarmine University Undergraduate Research Week. Todd, Patricia and S.D. Wilt. (2007) Are Snail1 and Snail2 activated in retinal pigment epithelium following vitreous treatment? Kentucky Academy of Sciences, University of Louisville and Bellarmine University Undergraduate Research Week. Metzler, M., Kupper, T. and Steven D. Wilt. (2006) Molecular aspects of proliferative vitreoretinopathy. Kentucky Academy of Science, Morehead State University, Morehead, KY. Lambert, R.C. Shepherd, C.W., Miller, K.M., Cashman, K.M and Steven D. Wilt. (2006) Comparative analysis of exon 1 for claudin 1, a tight junction molecule. Kentucky Academy of Science, Morehead State University, Morehead, KY. Miller, K. and S. Jenkins. (2006) Preliminary studies of Notch pathway activation in a cell culture model of proliferative vitreoretinopathy. Butler University Undergraduate Research Conference, Indianapolis, Indiana. Jenkins, S., Miller, K. and S.D. Wilt. (2006) Preliminary studies of Notch pathway activation in a cell culture model of proliferative vitreoretinopathy. 6th Annual Bellarmine University Undergraduate Research Poster Session, Louisville, KY. Shepherd, C.W., Miller, K.M., Cashman, K.M and Steven D. Wilt. (2005) Structural analysis of the claudin-1 gene, a tight junction molecule. Kentucky Academy of Science, Eastern Kentucky University, Richmond, KY. Howard, J.M. and I. Fehring. (2005) Identification of tight junction molecules in pig retinal pigment epithelium. Butler University Undergraduate Research Conference, Indianapolis, IN. Fehring, I. and J.M. Howard. (2005) A molecular and bioinformatics approach to identification of tight junction molecules in pig retinal pigment epithelium. 5th Annual Bellarmine University Undergraduate Research Poster Session, Louisville, KY. Grant, G. (2004) Neurotrophin-4 mRNA expression within the geniculate ganglion in varying ages of embryonic mice. 4th Annual Bellarmine University Undergraduate Research Poster Session, Louisville, KY. Madorsky, L. (2004) Impact of hyperbaric oxygen and UV light in vivo on guinea pig lens lipid oxidation and fluorophores. 4th Annual Bellarmine University Undergraduate Research Poster Session, Louisville, KY and Butler University Undergraduate Research Conference, Indianapolis, IN. Poster Presentations: Kojima, S., Reardon, E.J., Wilt, S.D., and L.J. Rizzolo. (2001) RPE alters claudin expression in different stages of tight junction development. Invest. Ophthalmol. Vis. Sci. 42S: 4025. Rizzolo, L.J., Peng, S. and S.D. Wilt. (2001) PDZ domains of ZO-2 modulate RPE tight junctions. Invest. Ophthalmol. Vis. Sci. 42S: 4026. Wilt, S.D. and L.J. Rizzolo. (2000) Overexpression of ZO-2 subdomains affects the regulation of RPE tight junctions. Invest. Ophthalmol. Vis. Sci. 41S: 2173. Wilt, S.D., Ban, Y. and L.J. Rizzolo. (1999) Alteration of tight junctions during the embryogenesis of retinal pigment epithelium (RPE). Mol. Biol. Cell 10S: 2368. McLaughlin, B.J., Greaton, C.J., Feng, W. and S.D. Wilt. (1998) Molecular studies of the mannose receptor. International Congress of Eye Research, Paris, France. Wilt, S.D. and B.J. McLaughlin. (1998) Identification of a 110kDa protein which may be related to the mannose receptor. Invest. Ophthalmol. Vis. Sci. 39S: 189. Wilt, S.D. and B.J. McLaughlin. (1996) NCAM in dystrophic retinas. Invest. Ophthalmol. Vis. Sci. 37S: 384. Greaton, C.J., Lane, K.B., Wilt, S.D., Shepherd, V.L. and B.J. McLaughlin. (1995) Expression of a phagocytic receptor in retinal pigment epithelium. The Ocular Cell and Molecular Biology Symposium II, San Diego, California. Wilt, S.D., Lutz, D.A., Seiler, M., Shepherd, V.L., and B.J. McLaughlin. (1995) Developmental expression of a phagocytic receptor during onset of phagocytosis. Invest. Ophthalmol. Vis. Sci. 36S: 550. Links of Interest:
NASCAR, softball, racquetball, running, in-line skating, home remodeling, scientific illustration Click HERE to go to the Bellarmine University Biology Department's page If you have questions or comments, email me at: swilt@bellarmine.edu Bellarmine University Send comments and questions to: swilt@bellarmine.edu The views and opinions expressed in this page are strictly those of the page author. The contents of this page have not been reviewed or approved by Bellarmine University.
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