The National Institute of Dental and Craniofacial Research has awarded Brian Schmidt of the Bluestone Center for Clinical Research at New York University College of Dentistry and Nigel Bunnett of Columbia University’s Departments of Surgery and Pharmacology, a $3.7 million, five-year grant to study proteases and neuronal signaling responsible for oral cancer pain.
Schmidt and Bunnett seek to identify the proteases—or enzymes that catalyze the breakdown of proteins—and signaling pathways that initiate and sustain oral cancer pain. Bunnett and Schmidt collaboratively investigated the role of proteases in oral cancer pain in 2009 when they were faculty at the University of California San Francisco.
Schmidt moved to NYU Dentistry in 2010 and Bunnett moved to Monash University in Australia in 2011. In August, 2016, Bunnett accepted the position of Vice Chair of Research in Surgery and Professor of Surgery and Pharmacology at Columbia University; once again in the same city, Bunnett and Schmidt renewed their collaboration.
Bunnett is an expert on G protein-coupled receptors—over many years, he investigated how proteases and a specific GPCR termed protease-activated receptor 2, mediate neurogenic inflammation and pain.
PAR2 is a signaling receptor that can be activated on the surface of a cell. Bunnett’s Nature Medicine publication in 2000 on the role of PAR2 and neurogenic inflammation set the stage for pioneering work that determined the role of PAR2 and TRPV in colitis, neurogenic inflammation, and pain. The role of PAR2 in cancer pain, however, remained unexplored.
Bunnett investigated PAR2 and endosomal signaling. During the signaling process, an activated cell surface receptor, such as PAR2, is internalized within endosomes—small membrane-bound compartments within a cell. Bunnett and Schmidt now propose to delineate the mechanism by which proteases associated with oral cancer initiate pain signaling through cell surface receptors and subsequently through endosomal signaling.
