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Proteinase control mechanisms
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The focus of our research is the study of the proteinases that
degrade the cornea and the inhibitors that control these molecules.
The cornea is a unique tissue for two reasons: the function of the
cornea depends upon transparency of the tissue, and the cornea
synthesizes most of its proteins because the cornea is an avascular
tissue. Control of the synthesis of proteinase and proteinase
inhibitors is critical in the function of the cornea.
Plasminogen, the precursor of the fibrinolytic enzyme plasmin, was
identified as a protein that is synthesized by corneal cells but not
by most other cells with the exception of hepatic cells. Most
tissues obtain plasminogen from the blood. Current studies are
directed towards understanding the mechanism by which plasminogen
synthesis is induced by corneal cells.
Corneal cells, unlike most non-malignant cells, convert plasminogen to
angiostatin. Angiostatin is a potent antiangiogenic molecule found in the
cornea. Current studies are focused on
determining the mechanism the cornea uses to convert plasminogen to
angiostatin.
Maspin is a SERPIN identified based on its downregulation in
epithelial cells upon acquisition of the malignant phenotype. In the
cornea not only do epithelial cells synthesize this molecule but also
corneal stromal cells. Current studies are focused on elucidation of
the function of maspin in the corneal stroma.
One of the major causes of corneal ulceration is bacterial
keratitis. Bacteria invasion of host tissues requires proteinases
that degrade host tissues. Our recent studies revealed that corneal
isolates of Pseudomonas aeruginosa synthesize a number of
uncharacterized proteinases. One of these enzymes is an elastase with
different properties than classical elastase. The processing as well
as the enzymatic properties of these proteinases is being studied.
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"Maspin: synthesis by human cornea and regulation of in vitro stromal cell adhesion to extracellular matrix.",
C. Ngamkitidechakul, J.M. Burke, W.J. O'Brien, S.S. Twining
Invest. Ophthalmol Vis. Sci., 42(13), 3135-41(2001)
"Functional characterization of arginine 30, lysine 40, and arginine 62 in Tn5 transposase.",
S.S. Twining, I.Y. Goryshin, A. Bhasin, W.S. Reznikoff
J. Biol. Chem., 276(25), 23135-23143 (2001)
"The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo.",
Z. Liu, X. Zhou, S.D. Shapiro, J.M. Shipley, S.S. Twining, L.A. Diaz, R.M. Senior, Z. Werb.
Cell, 102(5), 647-655 (2000)
"A disease-associated glycine substitution in BP180 (type XVII collagen) leads to a local destabilization of the major collagen triple helix.",
M. Olague-Marchan, S.S. Twining, M.K. Hacker, J.A. McGrath, L.A. Diaz, G.J. Giudice. Matrix Biol, 19(3), 223-233 (2000)
"Blood glucose laboratory for first-year medical students: an interdisciplinary model for nutrition-focused diabetes management.",
S.A. Reiter, C.R. McGill, S.L. Lawrence, S.S. Twining.
J. Am. Diet Assoc., 100(5), 570-572 (2000)
"A critical role for neutrophil elastase in experimental bullous pemphigoid.",
Z. Liu, S.D. Shapiro, X. Zhou, S.S. Twining, R.M. Senior, G.J. Giudice, J.A. Fairley, L.A. Diaz.
J Clin Invest,105(1), 113-123 (2000)
"Tn5: A molecular window on transposition.",
W.S. Reznikoff, A. Bhasin, D.R. Davies, I.Y. Goryshin, L.A. Mahnke, T. Naumann, I. Rayment, M. Steiniger-White, S.S. Twining.
Biochem Biophys. Res. Commun., 266(3), 729-734 (1999)
"Extrahepatic Synthesis of Plasminogen in the Human Cornea is Up-Regulated by Interleukins-1a and 1b",
S.S. Twining, P.M. Wilson, and C. Ngamkitdaichakul. Biochem.J., 339, 705-712 (1999)
"Local control of alpha1-proteinase inhibitor levels: regulation of alpha1-prote inase inhibitor in the human cornea by growth factors and cytokines"
G. Boskovic, S.S. Twining. Biochim Biophys Acta. 1403(1): 37-46 (1998).
"Involvement of Sp1 Elements in the Promoter Activity of the a1 Proteinase Inhibitor",
Y. Li, L. Zhou, S.S. Twining, J. Sugar, and B.Y.T. Yue, J.Biol.Chem., 273, 9959-9965 (1998)
"Retinol and Retinaldehyde Specifically increase a1-Proteinase Inhibitor in theHuman Cornea",
G. Boskovic and S.S. Twining. Biochem. J., 322,751-756 (1997).
"Changes in Rat Corneal Matrix Metalloproteinases and Serine Proteinases under Vitamin A Deficiency",
S.S. Twining, D.P. Schulte, P.M. Wilson, B. Fish and J. Moulder. Curr. Eye Res., 16, 156-165 (1997).
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