p53 counteracts reprogramming by inhibiting mesenchymal-to-epithelial transition.

The process of somatic cell reprogramming is gaining increasing interest as reprogrammed cells are considered to hold a great therapeutic potential. However, with current technologies this process is relatively inefficient. Recent studies reported that inhibition of the p53 tumor suppressor profoundly facilitates reprogramming and attributed this effect to the ability of p53 to restrict proliferation and induce apoptosis. Given that mesenchymal-to-epithelial transition (MET) was recently shown to be necessary for reprogramming of fibroblasts, we investigated whether p53 counteracts reprogramming by affecting MET. We found that p53 restricts MET during the early phases of reprogramming and that this effect is primarily mediated by the ability of p53 to inhibit Klf4-dependent activation of epithelial genes. Moreover, transcriptome analysis revealed a large transcriptional signature enriched with epithelial genes, which is markedly induced by Klf4 exclusively in p53(-/-) cells. We also found that the expression of the epithelial marker E-Cadherin negatively correlates with p53 activity in a variety of mesenchymal cells even before the expression of reprogramming factors. Finally, we demonstrate that the inhibitory effect of p53 on MET is mediated by p21. We conclude that inhibition of the p53-p21 axis predisposes mesenchymal cells to the acquisition of epithelial characteristics and renders them more prone to reprogramming. Our study uncovers a novel mechanism by which p53 restrains reprogramming and highlights the role of p53 in regulating cell plasticity.

A self-medication program for rehabilitation patients.

The purpose of this project was to develop and establish a self-medication program on the rehabilitation ward at Mount Sinai Hospital. Upon discharge most of the patients on this ward are responsible for the self-administration of medications, some of which they will be taking chronically. The objective of this program is to teach patients about their medications while still under medical supervision. Patients are counselled throughout the program by nurses and a pharmacist. Family members are also counselled on request. The program is completed by a final discussion with the patient prior to discharge. As a result of the program a manual was produced for use by pharmacy and nursing personnel to help define their respective roles in the program. Results of a patient survey indicated that a definite benefit was perceived by all patients who were helped to develop their ability to self-medicate. Errors made while in the hospital were discovered and corrected prior to discharge. Pharmacy time required to set up the program was, initially, extensive. Once the program was established, however, nursing medication administration time was greatly decreased and freed for other activities on the floor.