Signaling molecules called small GTPases regulate a wide variety of cellular processes, including cellular migration, proliferation, and adhesion. Misregulation of these molecules has been implicated in the progression of cancer. Essential for their proper subcellular localization and activity, small GTPases are prenylated to promote association with membranes. Our lab has recently uncovered a mechanism in which splice variants of SmgGDS control the entry of small GTPases into the prenylation pathway. I am interested in understanding the different mechanisms and signals that regulate the entrance of small GTPases into the prenylation pathway.
Additionally, signaling by adenosine has been shown to be very important in cancer. Elevated concentrations of adenosine have been observed in a variety of cancer tissues. Adenosine signals through four G-protein coupled receptors, each of which couple to different classes of G proteins. Upon adenosine binding its receptor, a variety of different signaling pathways can potentially be activated. The outcome, therefore, depends largely on the expression of the four adenosine receptor subtypes on the cell surface. Many of these outcomes are very important in cancer, including enhanced proliferation, immunosuppression, and angiogenesis. I am interested in discovering whether these downstream signaling pathways activated by adenosine tie into the prenylation of small GTPases.