Epithelial cells line the surface of various organs and are responsible for many important biological functions including secretion, absorption and protection. As the first line of defense in frequent contact with environmental carcinogens, epithelium-derived neoplasm (the carcinomas) account for over 90% of all human tumors. It is thus critically important to better understand the structure and function of epithelial cells. Our laboratory has shown earlier that keratins, a group of intermediate proteins that were thought to be uniquely associated with skin epidermis and its appendages such as hair and nail, are present in almost all epithelial cells and their neoplasm. We showed that specific basic and acidic keratins form keratin pairs that represent markers for different pathways and stages of epithelial differentiation. By studying keratin expression in corneal epithelium (Photo 2 above), we showed that corneal epithelial stem cells are not evenly distributed in the entire corneal epithelium. Rather, corneal epithelial stem cells are found to be limited to peripheral cornea in a narrow zone known as the limbus. In collaboration with Robert Lavker and George Cotsarelis, we showed that hair follicular epithelial stem cells are not located at the bottom of hair follicle in the hair root. Rather such hair follicular stem cells reside in upper follicle in the bulge area. More recently, our group discovered a group of four epithelial membrane proteins, called uroplakins, which are made by mammalian bladder urothelium as major differentiation products. We demonstrated that the four major uroplakins (UPIa, Ib, II and IIIa) form 2 heterodimeric pairs (Ia/II and Ib/IIIa) before they can exit from the ER and undergo further assembly to form a 16-nm proteins, which then assemble into hexagonally packaged 2D crystals called urothelial plaques (Photo 1, 3 and 4). These plaques cover almost completely the apical surface of bladder epithelium, and are required for the bladder epithelium to form a remarkable permeability barrier. We assembled a group of investigators (the NYU Urothelial Biology Group, which is an integral part of the NYU Center of Excellence on Urological Diseases) to study, using multidisciplinary approaches, the structure, function and disease implications of uroplakins and other urothelial membrane proteins. In training graduate and postdoctoral students, we emphasize scientific methods (Photo 5).