The main interest of our laboratory is to study regulated intramembrane proteolysis (RIP) and signal transduction. RIP has emerged as a novel-signaling paradigm in the new millennium. RIP refers to events wherein proteins are cleaved within the plane of cell membranes to liberate fragments for signal transduction, as indicated in the figure to the right. Examples are the processing events that govern sterol synthesis, Notch signaling, unfolded protein responses, amyloid precursor protein (APP) catabolism, and growth factor activation.
Intramembrane cleavage proteases not only serve as highly effective post-translational regulators of protein function but also represent a unique class of enzymes that catalyze substrate hydrolysis within transmembrane domains. Two intramembrane proteases -- gamma-secretase and Rhomboid-mediated intramembrane serine protease are under investigation in our lab, utilizing the powerful tools of molecular biology, protein chemistry, chemistry, and proteomics.
