Teaching Interests
Cell Biology; Cellular Junctions (desmosomes, hemidesmosomes, tight junctions, adherens; gap); Histology of the eye, connective tissues, and muscles; Integrins and the Extracellular Matrix; Rat and mouse development and use of transgenic mice as models.
Research
The structural properties of the cornea make it strong to best protect the retina from damage while at the same time maintaining clarity and its curved shape so it can focus light properly. The epithelial cells that cover the cornea are maintained by a population of stem cells located within a specialized stem cell niche at a site called the limbus. Because of its clarity and strength, the cornea and its stem cell niche can be viewed using state of the art imaging methods to give us insight into how it is arranged in health and disease. In our lab, we are studying the cornea and its niche to understand is how corneal epithelial stem cells are maintained within their niche in normal tissue homeostasis and in during wound healing.
In particular, we have focused on how epithelial cells adhere to the underlying extracellular matrix via proteins called integrins. We have shown that corneal epithelial stem cells express higher amounts of specific types of integrins. These integrins mediate attachment to and the organization of the underlying matrix by binding to matrix protein in the niche. We have also developed a mouse model that allows us to reproducibly induce corneal epithelial stem cell deficiency and recurrent epithelial erosions. This model will be useful in developing treatments to minimize both the development and the progression of stem cell deficiency and to allow us to begin to design treatments for patients suffering from this disease. Our next steps involve analysis of the timing of the changes that happen as stem cell deficiency develops and the stem cell niche becomes depleted of its stem cells. For in vitro experiments, we use primary cell cultures derived from wildtype mouse keratinocytes and keratinocytes derived from various transgenic and knockout mice. Techniques used in the lab include brightfield,and confocal microscopy, time lapse cell migration studies, analyses of protein expression and signal transduction pathways using immunoblotting, immunoprecipitation, reporter assays, and zymography as well as primary culture of mouse epithelial cells.
Our long term goals are to better our understanding of how the cells that make up the epithelial niche of the cornea are maintained and what happens to those cells and their niche when the tissue they serve is injured. To be able to prevent stem cell loss and recurrent corneal erosions, we need to understand how they happen and our animal models will allow us to do just that. This knowledge will lead to improved treatment of patients with corneal epithelial stem cell deficiency and recurrent corneal erosions. It will also enhance our knowledge of the factors that regulate proliferation of epithelial stem cells during tumor and pterygia development.
Current Members
- Ahdeah Pajoohesh-Ganji, Research Scientist- Email: ahdeah@gwu.edu
- Sonali Pal-Ghosh, Lab Manager - Email: spghosh@gwu.edu
- Gauri Tadvalkar, Research Associate - Email: guari@gwu.edu
- Stepp MA, Liu Y, Pal-Ghosh S, Jurjus RA, Tadvalkar G, Sekaran A, Losicco K, Jiang L, Larsen M, Li L, and Yuspa SH. 2007. Reduced migration, altered matrix and enhanced TGF?1 signaling are signatures of mouse keratinocytes lacking Sdc1. J. Cell Sci. 120, 2851-2863. PDF
- Vanhoutte D, Schellings MW, Gotte M, Swinnen M, Herias V, Wild MK, Vestweber D, Chorianopoulos E, Cortes V, Rigotti A, Stepp MA, Van de Werf F, Carmeliet P, Pinto YM, and Heymans S. 2007. Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction. Circulation. 115, 475-482.
- Stepp MA. 2006. Corneal integrins and their functions. Exp. Eye Res. 83:3-15. PDF
- Pajoohesh-Ganji A, Pal-Ghosh S, Simmons SJ, and Stepp MA, 2006. Integrins in slow cycling corneal epithelial cells in the mouse. Stem Cells 24:1075-1086. PDF
- Stepp MA and Zieske JD. 2005. The corneal epithelial stem cell niche. Ocul. Surf. 3, 15-26. PDF
- Pajoohesh-Ganji A. and Stepp MA. 2005. In search of markers for the stem cells of the corneal epithelium. Biol. Cell 97:265-276. PDF
- Pajoohesh-Ganji A, Pal-Ghosh S, and Stepp MA. 2004. Regional distribution of ?9?1 integrin within the limbus of the mouse ocular surface. Dev. Dyn. 230:518-528. PDF
- Pal-Ghosh S, Pajoohesh-Ganji A, and Stepp MA. 2004. A mouse model for the study of recurrent epithelial erosions demonstrates a role for a9b1 integrin in progression of disease. Invest. Ophthalmol.Vis. Sci. 45:1775-1785.PDF
- Tomczuk M, Takahashi Y, Huang J, Murase S, Mistretta M, Klaffky E, Sutherland A, Bolling L, Conrod S, Marcinkiewicz C, Sheppard D, Stepp MA, and White JM. 2003. Role of Multiple b1 Integrins in Cell Adhesion to The Disintegrins Domains of Adams 2 and 3. Exp. Cell Res. 290, 68-81.
- Stepp MA, Gibson HE, Gala PH, Sta.Iglesia DD, Pajoohesh-Ganji A, Pal-Ghosh S, Brown M, Aquino C, Schwartz AM, Goldberger O, Hinkes MT, and Bernfield M. 2002. Defects in keratinocyte activation during wound healing in the syndecan-1 deficient mouse. J.Cell Sci., 115, 4517-4531. PDF
- Belkin AH and Stepp MA. 2000. Integrins as Receptors for Laminins. Microscopy Research Techniques 51, 280-301.
- Sta. Iglesia DD and Stepp MA. 2000. Disruption of the Basement Membrane After Corneal Debridement. Invest. Ophthal. Vis. Sci.: 41, 1045-1053.
- Sta. Iglesia DD, Gala PH, Qiu T, and Stepp MA. 2000. Integrin Expression During Epithelial Migration and Restratification in the Tenascin-C-deficient Mouse Cornea. J. Histochemistry and Cytochemistry, 48, 363-376.