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Noorjahan Panjwani,
PhD
Director
of Research,
Department of
Ophthalmology,
New England Eye Center
Professor
of Ophthalmology
and Biochemistry,
Tufts University School of Medicine
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Education
PhD, Biology, University of Oxford
Glycobiology, Harvard Medical School (Dr. Robert
Spiro's Lab)
Research Interests
Acanthamoeba parasites
produce sight-threatening corneal infection, especially in contact
lens wearers. Adhesion of the organism to the surface of the cornea
is clearly a critical first step in the pathogenesis of infection.
Our goals in the recent past have been to delineate the mechanism
by which the amoebae adhere to the surface of the cornea and cause
cytolysis and necrosis of host tissues. We have demonstrated that
the amoebae adhere to the surface of corneal epithelium via a
mannose binding protein and that subsequent to the adhesion, amoebae
secrete a cytotoxic metalloproteinase. We have found novel methods
to inhibit the adhesion of amoebae to host cells and to inhibit
the parasite's ability to produce cytotoxic proteinases. Our goals
are to find a means to identify individuals who are at risk of
developing the infection by testing their tear samples and to
provide them with rationally designed strategies to protect against
the infection. These studies also contribute significantly to
the core mechanisms of cell biology.
In recent years, we have been investigating
the role of carbohydrate-binding proteins, galectins, in corneal
epithelial sheet migration, a key event in corneal epithelial
wound healing. Studies from my laboratory have suggested that
specifically galectin-3 plays a role in events which mediate corneal
epithelial sheet migration. We are currently investigating the
mechanism by which galectin-3 mediates corenal epithelial sheet
migration and wound closure. Our goal is to deleniate specific
signal transduction pathways which may be modulated by galectins.
We hope that these studies will contribute to a better understanding
of the molecular mechanisms that mediate migration of the corneal
epithelial sheet over the wound surface and will ultimately help
find novel methods to promote corneal epithelial wound closure
in patients suffering from nonhealing epithelial defects.
In addition, we are investigating the mechanisms
that mediate corneal epithelial cell-cell adhesion. Our recent
studies have demonstrated that specifically, a corneal epithelial
cell surface glycoprotein carrying a carbohydrate antigen, LewisX,
plays a key role in corneal epithelial cell-cell adhesion. This
glycoprotein also appears to play a role in corneal epithelial
cell differentiation. The synthesis of the Lewis-X oligosaccharides
is mediated by alpha(1,3)fucosyltransferases. In this project,
our goals are to characterize the core protein of the LewisX-glycoprotein
and fucosyltransferases of corneal epithelium with respect to
their function in diseases processes of the cornea.
Representative Publications
Garate M, Cubillos I, Marchant
J, Panjwani N. Biochemical characterization
and functional studies of Acanthamoeba mannose-binding
protein. Infect Immun. 2005 Sep;73(9):5775-81.
Diskin, S, Kumar, J, Cao,
Z, Schuman, JS, Gilmartin, T, Head, SR, Panjwani
N. Detection
of Differentially Expressed Glycogenes
in Trabecular Meshwork of Primary Open-Angle
Glaucoma Eyes. In press IOVS
Garate, M, Marchant, J,Cubillos, I,Cao,
Z, Khan, NA, Panjwani
N. In vitro Pathogenicity
of Acanthamoeba is Associated with the Expression
of the Mannose-Binding Protein. In press
IOVS
Cao Z, Said N, Wu HK, Kuwabara
I, Lui F-T, and Panjwani N:
Galectin-7. a potential mediator of corneal
epithelial cell migration. Arch Opthalmol
121:82-86, 2003
Cao Z, Said N, Amin S, Wu HK, Bruce
A, Garate M, Hsu, DK, Kuwabara I,
Lui FT, and Panjwani N. Galectins-3
and -7, but not galectin-1, play
a role in re-epithelialization of
wounds. J Biol Chem 277:42299-42305,
2002
Cao, Zhiyi, Helen K. Wu, Amenda Bruce, Kurt Wollenberg,
Fu-Tong Liu, and Panjwani
N. Detection of differentially expressed genes in healing
mouse corneas using cDNA microarrays. Invest Opthalmol Vis Sci 43:2897-2904, 2002
(Microarray Data Files)
Cao Z, Zhao Z, Alroy JL, Stanley P, and Panjwani
N: A Potential Role for the Lewisx Glycan Determinant in
Corneal Epithelial Cell Adhesion and Differentiation. J Biol Chem
276:21714-21723, 2001
Khan NA, Harroll EL, Panjwani N,
Cao ZY, and Paget TA: Proteases as markers for differentiation
of pathogenic and nonpathogenic species of Acanthamoeba. J Clin
Microbiol 38:2858-2861, 2000.
Terraciano AJ, Wang N, Schuman JS, Haffner G, Panjwani
N, Zhao Z, and Yang Z: Sialyl Lewis X, Lewis X, and N-acetyllactosamine
expression on normal and glaucomatous eyes. Curr Eye Res 18:73-78,
1999.
Cao Z, Jefferson DM, and Panjwani N:
Role of carbohydrate-mediated adherence in cytopathogenic mechanisms
of Acanthamoeba. J Biol Chem 273:15838-5845, 1998.
Paliakkara-Lona J, Cao Z, and Panjwani
N: Binding of Acanthamoeba
to mannose-glycoproteins of corneal epithelium: effect of injury.
Curr Eye Res 17:770-776, 1998
Panjwani N, Zhao Z., Baum J,
Hazlett, LD, and Yang Z: Acanthamoeba
bind to rabbit corneal epithelium in vitro. Invest Ophthalmol
Vis Sci 38:1858-1864, 1997.
Yang Z, Cao Z and Panjwani N:
Pathogenesis of Acanthamoeba
keratitis: carbohydrate-mediated host-parasite interactions. Infect
Immun 65:439 -445, 1997.
Panjwani N, Zhao Z, Raizman M,
and Jungalwala F: Pathogenesis of corneal infection: binding of
Pseudomonas aeruginosa to specific
phospholipids. Infect Immun 64:1819-1825, 1996.
Yang Z, Zhao Z, and Panjwani
N: Gangliosides of migrating and nonmigrating corneal epithelium
in organ and cell culture. Invest Ophthalmol Vis Sci 37:501-510,
1996.
Mohan R, Lee B, and Panjwani N:
Molecular cloning of the E-cadherin cDNAs from rabbit corneal
epithelium. Curr Eye Res 14:1135-1145, 1995.
Panjwani N, Zhao Z, Ahmad S,
Yang Z, Jungalwala F, and Baum J. Neolactoglycosphingolipids,
potential mediators of corneal epithelial cell migration. J Biol
Chem 270:14015-14203, 1995.
Book Chapters
Panjwani N:
Cornea and Sclera In Harding
JJ (ed): Biochemistry of the Eye. Chapman and Hall Ltd, London,
pp 16-51, 1997
Panjwani N and
Mohan R: Sclera. In Krachmer
J, Mannis N, and Holland E (eds): Cornea. Mosby Year Book, St.
Louis, pp 29-40, 1997
Vision
Research Laboratories
Tufts Center
for Vision Research
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