Noorjahan Panjwani, PhD
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Education
PhD, Biochemistry, University of Oxford
Postdoctoral Training
Glycobiology, Harvard Medical School (Dr. Robert Spiro's Lab)
Research Interests
Dr. Panjwani is a glycobiologist specializing in investigating the role carbohydrate-binding proteins in diseases of the eye.
General Comments: In recent years, carbohydrate-binding proteins have been shown to play a pivotal role in fundamental biological processes. One of the most well-known examples is the role of selectins in extravasation of leukocytes from the blood to the sites of inflammation (click here or on the graphic below for full amination and more information).
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Specific Projects: We study the role of carbohydrate-binding proteins in the pathogenesis of wound healing, angiogenesis, and corneal infections. Specifically, we are characterizing the role of carbohydrate-based recognition in signaling processes leading to the development of blinding corneal diseases. All projects in the lab have a solid basic science component to understand cell biological and biochemical mechanisms of wound healing and angiogenesis, and are disease-oriented with a focus on translational research to find better, novel ways to treat blinding diseases of the eye.
Below is the summary of our recent findings.
1. The role of carbohydrate-based recognition in Angiogenesis
Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a tightly regulated process involved in the pathogenesis of a number of blinding diseases including corneal graft rejection, corneal wound healing and age-related macular degeneration. The process of angiogenesis begins when the endothelial cells (EC) of a mature blood vessel wall are activated by angiogenic factors such as VEGF and bFGF. Activation promotes loosening of EC from their basement membrane and the supporting peri-endothelial cells, thereby allowing EC to migrate, proliferate, and ultimately form capillary lumen. Recent studies in the lab have suggested that that a carbohydrate-binding protein, galectin-3, plays a key role in the regulation of VEGF- and bFGF-mediated angiogenesis. Specifically, we have shown that loss of galectin-3 function by siRNA knockdown results in the reduction of angiogenic response to VEGF and bFGF in vitro and that VEGF- and bFGF-mediated angiogenesis in vivo is reduced in galectin-3 knockout mice. Furthermore, we found that loss of high affinity galectin-3 ligands by disruption of a glycosyltransferases, GnTV, markedly decreases VEGF- and bFGF- mediated angiogenesis. These data lead us to conclude that galectin-3 modulates VEGF- and bFGF-mediated angiogenic response, and therefore, potent inhibitors of galectin-3 may serve as valuable targets for treatment of a number of blinding diseases of the eye as well as nonocular conditions such as cancer, rheumatoid arthritis and diabetes.
2. The role of carbohydrate-based recognition in re-epithelialization of wounds
Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, are painful, and are difficult to treat. In most cases, failure of re-epithelialization is not attributed to inadequate cell proliferation but is the result of a reduced potential of the epithelium to migrate across the wound bed. Recent studies have provided evidence that carbohydrate-based recognition plays a pivotal role in cell migration and re-epithelialization of wounds. We have demonstrated that: (i) migrating epithelium of healing mouse corneas express elevated levels of Gal-3 compared to nonmigrating epithelium of normal corneas, (ii) the rate of re-epithelialization of corneal wounds is significantly slower in Gal-3-deficient mice compared to the wild-type mice, and (iii) exogenous Gal-3 stimulates re-epithelialization of corneal wounds. The first step in the cascade of events leading to cell migration is the polarization and extension of cellular protrusions such as lamellipodia and filopodia. More recent studies in the lab have demonstrated that: (i) Gal-3 promotes formation of lamellipodia by activating Rac1 GTPases in epithelial cells and that (ii) carbohydrate-mediated interaction between Gal-3 and complex N-glycans on α3β1 integrins is involved in Gal-3-induced lamellipodia formation.
3. The role of carbohydrate-based recognition in corneal infection
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 biochemical and cell biological mechanisms of infections in general.
Submitted Articles
- Diskin S, Cao Z, Gong H, Soza A, Gonzalez A and Panjwani N: Galectin-8
Promotes cytoskeletal rearrangement in trabecular meshwork cells through activation of rho signaling. Invest Ophthalmol Vis Sci (In revision, 2008). - Diskin S, Cao Z, Leffler H and Panjwani N: The role of integrin glycosylation in galectin-8-mediated trabecular meshwork cell adhesion and spreading. Glycobiology (Submitted, 2008).
- Markowska A, Liu F and Panjwani N: Galectin-3 is an important mediator of VEGF-and bFGF- mediated angiogenic response. (Submitted, 2008).
- Saravanan C, Liu F, Gipson I and Panjwani N: Galectin-3 promotes lamellipodia formation in epithelial cells by interacting with complex N-glycans on a3b1 Integrins.
(Submitted to J Cell Science 2008).
Selected Publications:
- Diskin S. and Panjwani N: Carbohydrate-Based Recognition Systems in Primary Open Angle Glaucoma Curr Org Chem. Vol 12, No. 11, pp 911-917, 2008 (Invited Review)
- Saravanan C, Cao Z, Kumar J, Qiu J, Plaut A, Newburg D, Panjwani N: Milk components inhibit Acanthamoeba-induced cytopathic effect. Invest Ophthalmol Vis Sci. 2008 Mar:49(3):1010-5.
- Cao Z, Saravanan C, Goldstein MH, Wu HK, Pasricha G, Sharma S, and Panjwani N: Human tears inhibit Acanthamoeba-induced cytopathic effect. Arch Ophthalmol. 2008, Mar:126(3):348-52.
- Garate M, Alizadeh H, Neelam S, Niederkorn J, and Panjwani N: Oral immunization with Acanthamoeba mannose-binding protein provides protection against amoebic keratitis. Infect Immun, 2006, Dec:74(12):7032-7034.
- Diskin S, Kumar J, Cao Z, Schuman JS, Gilmartin T, Head SR, Panjwani N. Detection of differentially expressed glycogenes in trabecular meshwork of eyes with primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1491-9.
- 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. Invest Ophthalmol Vis Sci. 2006 Mar;47(3):1056-62.
- 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.
- Garate M, Cao Z, Bateman E, Panjwani N. Cloning and characterization of a novel mannose-binding protein of Acanthamoeba. J Biol Chem. 2004 Jul 9;279(28):29849-56.
- Ishida K, Panjwani N, Cao Z, Streilein JW. Participation of pigment epithelium in ocular immune privilege. Epithelia cultured from iris, ciliary body, and retina suppress T-cell activation by partially non-overlapping mechanisms. Ocul Immunol Inflamm. 2003 Jun;11(2):91-105.
- Haber M, Cao Z, Panjwani N, Bedenice D, Li WW, Provost PJ. Effects of growth factors (EGF, PDGF-BB and TGF-beta 1) on cultured equine epithelial cells and keratocytes: implications for wound healing. Vet Ophthalmol. 2003 Sep;6(3):211-7.
- Cao Z, Said N, Wu HK, Kuwabara I, Liu FT, Panjwani N. Galectin-7 as a potential mediator of corneal epithelial cell migration. Arch Ophthalmol. 2003 Jan;121(1):82-6.
- Cao Z, Wu HK, Bruce A, Wollenberg K, Panjwani N. Detection of differentially expressed genes in healing mouse corneas, using cDNA microarrays. Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2897-904.
- Cao Z, Said N, Amin S, Wu HK, Bruce A, Garate M, Hsu DK, Kuwabara I, Liu FT, Panjwani N. Galectins-3 and -7, but not galectin-1, play a role in re-epithelialization of wounds. J Biol Chem. 2002 Nov 1;277(44):42299-305.
- Cao Z, Zhao Z, Mohan R, Alroy J, Stanley P, Panjwani N. Role of the Lewis(x) glycan determinant in corneal epithelial cell adhesion and differentiation. J Biol Chem. 2001 Jun 15;276(24):21714-23.
