Noorjahan Panjwani, PhD
PhD, Biochemistry, University of Oxford
Glycobiology, Harvard Medical School (Dr. Robert Spiro's Lab)
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).
Specific Projects: We study the role of carbohydrate-binding proteins in the pathogenesis of the diseases of the cornea including persistent epithelial defects, corneal neovascularization, graft rejection and infections . 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.
1. The role of a carbohydrate-binding protein, galectin-3, in re-epithelailization of corneal wounds and angiogenesis
It is well established that transmembrane integrin receptors and growth factor receptors play a crucial role in re-epithelialization of wounds and angiogenesis. Although, almost all cell surface receptors including integrins, growth factor receptors and cytokine receptors are glycosylated proteins, they have been relatively under-investigated in the context of their glycosylation patterns. Our studies represent the leading edge of our current biochemical understanding of how the glycosylation pattern of cell surface receptors regulates their function (1-6) For example, in recent studies we have shown that: (i) a carbohydrate binding protein, galectin-3, promotes reepithelialization of corneal wounds, and that, it does so by activating α3β1-integrin–Rac1 signaling in epithelial cells (4) and (ii) galectin-3 modulates VEGF- and bFGF-mediated angiogenesis by binding to the N-glycans of integrin avb3, and subsequently activating the signaling pathways that promote the growth of new blood vessels (6). These findings have broad implications for developing novel, carbohydrate-based therapeutic agents for inhibition of angiogenesis. Our studies are highly clinically relevant and have resulted in two patent applications involving the use of: (i) carbohydrate-binding protein galectins for the treatment of dry eye and nonhealing epithelial defects and (ii) saccharide-based reagents to protect against corneal infections by inhibiting the adhesion of the microbes to the surface of the cornea.
- Markowska A, Liu FT and Panjwani N. (2010) Galectin-3 is an important mediator of VEGF and bFGF-mediated angiogenic response. J. Exp. Med. 207(9) 1981-1993. PMID 20713592
- Argüeso P, Guzman-Aranguez A, Mantelli F, Cao Z, Ricciuto J and Panjwani N. (2009). Association of cell surface mucins with galectin-3 contributes to the ocular surface epithelial barrier. J Biol Chem. 284(34),23037-45 PMID 19556244
- Saravanan C, Liu FT, Gipson IK and Panjwani N. (2009). Galectin-3 promotes lamellipodia formation in epithelial cells by interacting with complex N-glycans on a3b1 integrin. J Cell Sci., 122(Pt 20),3684-93. PMID 1975493
- Diskin S, Cao Z, Leffler H and Panjwani N. (2009). The role of integrin glycosylation in galectin-8-mediated trabecular meshwork cell adhesion and spreading. Glycobiology,19(1), 29-37. PMID 18849583.
- Cao Z, Said N, Wu HK, Kuwabara I, Liu FT, Panjwani N. (2003). Galectin-7 is a potential mediator of corneal epithelial cell migration. Arch Ophthalmol., 21(1),82-6. PMID12523890
- Cao Z, Said N, Amin S, Wu HK, Bruce A, Garate M, Hsu DK, Kuwabara I, Liu FT, Panjwani N. (2002). Galectins-3 and -7, but not galectin-1, play a role in re-epithelialization of wounds. J Biol Chem., 277(44),42299-305. PMID 1914966
2. 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.
- 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.
- 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.
- Cao Z, Jefferson DM, Panjwani N. Role of carbohydrate-mediated adherence in cytopathogenic mechanisms of Acanthamoeba. J Biol Chem. 1998 Jun 19;273(25):15838-45.