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NYU and Columbia Researchers Awarded NIH Grant to Investigate Proteases and Pain Signaling Related to Oral Cancer

Pictured left to right: Nigel Bunnett, PhD, and Brian Schmidt, DDS, MD, PhD. NYU IMAGE

The National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health (NIH), has awarded Brian Schmidt, DDS, MD, PhD, of the Bluestone Center for Clinical Research at New York University College of Dentistry (NYU Dentistry) and Nigel Bunnett, PhD, of Columbia University’s Departments of Surgery and Pharmacology, a $3.7 million, 5-year grant to study proteases and neuronal signaling responsible for oral cancer pain.

The pain signaling mechanisms responsible for cancer pain are not well understood. 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 both faculty at the University of California San Francisco.

Bunnett is an internationally recognized expert on G protein-coupled receptors (GPCR); over many years he investigated how proteases and a specific GPCR termed PAR2(protease-activated receptor 2), mediate neurogenic inflammation and pain. PAR2 is a signaling receptor that can be activated on the surface of a cell.

More recently  Bunnett investigated PAR2 and endosomal signaling. During the signaling process an activated cell surface receptor, such as PAR2, is internalized within endosomes.  Bunnett adds, “An activated receptor apparently continues its signaling role while contained in an endosome; to confirm this finding I investigated delivery of pain attenuating drugs into endosomes.” They 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.

Bunnett and Schmidt now seek to unequivocally identify tumor-generated proteases and define the signaling pathway from proteases to receptors on the surface of a nerve to the endosomes within the nerve.  Schmidt will utilize pain severity data gathered from his patients along with oral cancer tissue obtained during surgical resection.

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