NYU Dentistry Awarded Department of Defense Grant to Investigate the Causes of Oral Cancer Pain
Project will address a neglected issue that extracts an enormous toll on our injured soldiers and veterans: chronic pain and oral cancer pain.
The Department of Defense has awarded Yi Ye, PhD, a three-year grant in excess of $700,000 to expand her research into how oral cancer causes pain. The grant began on September 30, 2022 (award number W81XWH2210723).
Ye, an assistant professor of oral and maxillofacial surgery and of molecular pathobiology at NYU Dentistry and associate director for clinical research operations at the NYU Dentistry Translational Research Center, studies the neurobiology of oral cancer pain. Her research seeks to understand how pain is caused by complex, maladaptive molecular and cellular events. The goal is to trace the central modulator for such maladaptation so that pain can possibly be treated together with other comorbidities.
Active military personnel and veterans represent a large population of individuals suffering from chronic pain due to multiple types of traumatic injuries and disease, including oral cancer. Chronic pain and its effect on quality of life increase the risk for depression and suicide. Most chronic neuropathic pain disorders are resistant to current treatments. One of the impediments to understanding the causes of oral cancer pain includes a lack of knowledge of molecular and cellular interaction in the tumor microenvironment and surrounding nerves.
In the newly funded study, Ye and her team propose to investigate the role of a versatile protein called low-density lipoprotein receptor related protein (LRP1) in oral cancer pain. LRP1 serves diverse functions including lipid metabolism, protease degradation, anti-inflammation and tumor suppression. The research will focus on Schwann cells, a type of nerve cells found in the peripheral nervous system.
Ye’s collaborator, Wendy Campana, PhD, professor of anesthesiology at the University of California San Diego, has shown previously that LRP1 in Schwann cells regulates neuroinflammation (or inflammation around the nerve). The lack of LRP1 in Schwann cells accelerates immune cell accumulation to the site of nerve injury, leading to neuropathic pain-like conditions in rodent models. In previous studies, Ye has shown that Schwann cells play an important role in promoting cancer cell aggressiveness and pain. Schwann cells are critically involved in perineural invasion, a process of cancer spreading to nerves, which is associated with increased pain in patients. In a new model Ye and her team developed specifically to study perineural invasion, they found a significant presence of immune cells inside and surrounding the peripheral nerve.
Limited knowledge exists regarding the significance of neuroinflammation in pain and oral cancer progression. Accordingly, in this new DoD funded project, Ye and her team aim to identify subtypes of immune cells important to cancer pain, and to investigate whether Schwann cell LRP1 is involved in orchestrating cancer-associated neuroinflammation, and the subsequent impact of neuroinflammation on tumor progression and pain. They will also test the efficacy of two newly developed drugs that target LRP1 for oral cancer pain treatment.
Ye expects that this project will foster work in a new direction in oral cancer pain research, while addressing a neglected issue that takes a toll on injured soldiers and veterans: chronic pain and oral cancer pain. “This work,” says Ye, “will substantially expand our understanding of oral cancer chronic pain mechanisms and potentially facilitate oral cancer pain treatment for civilians and military personnel.”