Our lab primary research focus is the stem cells of the limbal-corneal epithelial lining regenerative approaches when this lining is compromised by the loss or malfunction of these stem cells. The cornea refracts incoming light to generate a focused image on the retina. Biological deficiencies or loss of the stem cells locate exclusively on the narrow outer limbal rim allow invasion of the central corneal surface by the related, but distinct, pro-vascular epithelia of the surrounding conjunctiva. This invasion leads to swelling, and neovascularization of the central corneal zone and facilities the development of infections and permanent scars. Partial or full blindness ensues. Hence, we are advocated at defining the features of these corneal stem cells and develop sources for their replenishment through in vitro stem cell expansion or de novo generation by guided reprograming of induced pluripotent stem cells(iPSCs). For the later purpose we are currently exploring how the transient ectopic expression of the master gene for corneal bio genesis (PAX6) redirects a known default spontaneous differentiation of iPSCs into ectodermal epithelial towards the specific limbal-corneal epithelial phenotype, as it seems to occur during natural embryonic and fetal development in humans. Studies of optimization of in vitro limbal stem cells expansion and their application to regenerative medicine in animal models and blind patients are carried out in collaboration with clinically oriented laboratories at the Catholic University of Korea, Seoul, Korea and The Department of Ophthalmology at Ege University in Izmir, Turkey. The laboratory second area of interest is the biological mechanisms that underpin exfoliation syndrome (XFS), an age-related and gene and environmental factor induced syndrome. While XFS is a systemic syndrome related to the aggregation associate with Alzheimer’s, Huntington’s and age- related macular degeneration. XFS most obvious impact is the generation of protein aggregates within the aqueous (watery) spaces of the eye. These deposits clog the sieving area through which they constantly generate aqueous exit the eye increasing intraocular pressure. In turn, the elevated intraocular pressure causes glaucoma, the death of the neurons that carry visual information to the brain. In collaboration with Dr Audrey Bernstein from this Department and Dr. Robert Ritch from the New York Eye and Ear Infirmry of Mount Sinai, we have recently demonstrated that XFS cells display reduced capacity to perform removal of emerging intracellular protein and organelle debris (autophagy). This overt dysfunctional phenotype which may also prevent the XFS cells from performing the constant extracellular matrix reengineering via proteolytic enzyme secretion and denatured protein endocytosis. The impaired housekeeping allows the formation of large denatured protein aggregates that characterize XFS.