The focus of the Kulkarni lab relates to understanding the signaling patwhays that promote growth and proliferation of islet cells. The lab has an interest in molecules that link growth factor signaling with proteins and pathways that also modulate tumor and uncontrolled proliferation. For example, p53 is a transcription factor which is the most frequently altered gene in human cancer. Mice deficient for p53 are developmentally normal but suceptible to spontaneous tumours. p53 is a cellular stress sensor leading to cell-cycle arrest, DNA repair, cellular senescence and apoptosis. We study the coordination and communication between the Insulin/IGF-1 and p53 signaling pathways in pancreatic islet growth. We are also intersted in the relevance of leptin signaling in the regulation of patheays that promote enhanced proliferation of progenitors in the adipocyte and endocrine lineages. We are undertaking studies to examine how mutations in the leptin receptor can modluate the ability of induced pluripotent stem cells to prolferate and differentiate towards different cell types.