Sally Twining, PhD
Professor of Biochemistry
Professor of Ophthalmology
Phone: (414) 456-8431
Address: Medical College of Wisconsin
Department of Biochemistry
8701 Watertown Plank Road
Milwaukee, WI 53226
Sally Twining, PhD is interested in the mechanism of corneal ulceration and means for controlling corneal degradation. Corneal ulceration can be induced by bacteria, viruses, autoimmune reactions, nutritional deficiencies, chemical injuries and genetic deficiencies. Degradation of the cornea occurs when there is an imbalance between proteinases, enzymes that degrade the cornea, and proteinase inhibitors. This imbalance can occur due to over synthesis of proteinases or inhibition of synthesis of proteinase inhibitors by the cornea or release of proteinase from bacteria or inflammatory cells. Dr. Twining's research centers around corneal ulceration due to Pseudomonas aeruginosa and vitamin A deficiency. As part of this research, the mechanisms by the cornea defends itself against degradation are studied. Understanding the molecular basis of corneal ulceration and how the normal cornea protects itself will lead to better ways of treating corneal ulceration.
Recently Dr. Twining's laboratory characterized a more active form of Pseudomonas elastase that is synthesized by 85% of the Pseudomonas aeruginosa organisms recovered from ulcerating corneas. Her laboratory also showed that the cornea can synthesize molecules that usually are synthesized by the liver and distributed to the tissues through the circulatory system. These include the proteinase that degrades fibrin, plasmin, and the proteinase inhibitors, (1-proteinase inhibitor ((1-antitrypsin), (1-antichymotrypsin and (2-macroglobulin. Plasmin is required for remodeling of the cornea following injury and inflammation. The proteinase inhibitors protect the cornea from degradation by proteinases are synthesized by the cornea and those released by inflammatory cells. In collaboration with Dr. Beatrice Yue at the University of Illinois School of Medicine, the pathogenesis of keratoconus, a corneal thinning disease, was shown to involve an imbalance between proteinases and inhibitors.
Post Doctoral Training
Immunology, Mayo Clinic Foundation
Biochemistry, Medical College of Wisconsin
Current Research Interests
Role of Proteinases in Corneal Ulceration
Effects of Vitamin A on the Cornea
Mechanism of Action of Proteinase Inhibitors
Honors and Society Memberships
Member, Visual Science A, NIH Study Section (1994-1998)
Grant Reviewer, USDA, NSF (1991-present)
American Association for Advancement of Science
American Chemical Society
American Society for Biochemistry and Molecular Biology
Association for Research in Vision and Ophthalmology
Wang L, Pedroja BS, Meyers EE, Garcia AL, Twining SS, Bernstein AM. Degradation of internalized αvβ5 integrin is controlled by uPAR bound uPA: effect on β1 integrin activity and α-SMA stress fiber assembly. PLoS One. 2012;7(3):e33915.
Warejcka DJ, Narayan M, Twining SS. Maspin increases extracellular plasminogen activator activity associated with corneal fibroblasts and myofibroblasts. Exp Eye Res. 2011 Nov;93(5):618-27. Epub 2011 Jul 27.
Narayan M, Mirza SP, Twining SS. Identification of phosphorylation sites on extracellular corneal epithelial cell maspin. Proteomics. 2011 Apr;11(8):1382-90. doi: 10.1002/pmic.201000362. Epub 2011 Mar 1.
White MJ, He H, Penoske RM, Twining SS, Zahrt TC. PepD participates in the mycobacterial stress response mediated through MprAB and SigE. J Bacteriol. 2010 Mar;192(6):1498-510. Epub 2010 Jan 8.
Bohnsack RN, Patel M, Olson LJ, Twining SS, Dahms NM. Residues essential for plasminogen binding by the cation-independent mannose 6-phosphate receptor. Biochemistry. 2010 Jan 26;49(3):635-44.
Narayan M, Twining S. Focus on molecules: maspin. Exp Eye Res. 2010 Jan;90(1):2-3. Epub 2009 Jul 15.
Horswill MA, Narayan M, Warejcka DJ, Cirillo LA, Twining SS. Epigenetic silencing of maspin expression occurs early in the conversion of keratocytes to fibroblasts. Exp Eye Res. 2008 Apr;86(4):586-600. Epub 2008 Jan 12.
Ayala A, Warejcka DJ, Olague-Marchan M, Twining SS. Corneal activation of prothrombin to form thrombin, independent of vascular injury. Invest Ophthalmol Vis Sci. 2007 Jan;48(1):134-43.
Warejcka DJ, Twining SS. Specific conformational changes of plasminogen induced by chloride ions, 6-aminohexanoic acid and benzamidine, but not the overall openness of plasminogen regulate, production of biologically active angiostatins. Biochem J. 2005 Dec 15;392(Pt 3):703-12.
Ayala A, Warejcka DJ, Vaughan KA, Twining SS, Yue BY. The fibrinolysis inhibitor alpha2-antiplasmin in the human cornea. Curr Eye Res. 2005
Warejcka DJ, Vaughan KA, Bernstein AM, Twining SS. Differential conversion of plasminogen to angiostatin by human corneal cell populations. Mol Vis. 2005 Oct 20;11:859-68.