Research in Focus

“Gates of Heaven” Calcium Channel Drives Oral Cancer Pain and Growth

ORAI1 fuels oral cancers — and may provide promising therapeutic target

An essential protein that acts as a gatekeeper for calcium entering cells promotes the growth of oral cancer and generates pain, according to a new study published in Science Signaling led by NYU Dentistry researchers.

“Our results show that ORAI1 channels — named after the three sisters in Greek mythology who guarded the gates of heaven — fuel the growth of oral cancer tumors and produce an abundance of molecules that, once secreted, interact with neurons resulting in an increased sensitivity to pain,” said Ga-Yeon Son, a postdoctoral fellow in the Department of Molecular Pathobiology and the study’s first author.

“Calcium entering cells is necessary for many good things, but too much calcium for a long time has the opposite effect,” said Rodrigo Lacruz, professor of molecular pathobiology and the study’s senior author.

In collaboration with NYU Pain Research Center scientists Rajesh Khanna, professor of molecular pathobiology, director of the NYU Pain Research Center, and a coauthor of the study, and Yi Ye, professor of molecular pathobiology, the team looked at the levels of a calcium-dependent enzyme called matrix metalloprotease 1 (MMP1) that is secreted outside of cancer. MMP1 is abundant in multiple types of cancer, including oral cancer cells, where its overexpression is associated with metastasis and poor prognosis.

“Future research will focus on targeting the ORAI1 channel in oral cancer to see if that can prevent or delay the progression from oral epithelial dysplasia to oral cancer tumors and concurrently alleviate the pain burden experienced by oral cancer patients,” added Son.

Gene Therapy Treats Chronic Pain by Dialing Down Sodium

Researchers at the NYU Pain Research Center have developed a gene therapy that treats chronic pain by indirectly regulating a specific sodium ion channel, according to a new study published in the Proceedings of the National Academy of Sciences. (PNAS). The innovative therapy, tested in cells and animals, is made possible by the discovery of the precise region where a regulatory protein binds to the NaV1.7 sodium ion channel to control its activity.

Scientists have been trying for years to develop pain treatments to selectively block NaV1.7, a sodium ion channel, which can be harnessed to provide relief from chronic pain with little success. Raj Khanna, PhD, professor of molecular pathobiology and director of the NYU Pain Research Center, has taken a different approach: rather than blocking NaV1.7, his goal is to indirectly regulate it using a protein called CRMP2, which “talks” to the sodium channel and regulates its activity, allowing more or less sodium into the channel.

“We found a way to take an engineered virus — containing a small piece of genetic material from a protein that all of us have — and infect neurons to effectively treat pain,” said Dr. Khanna. “We are at the precipice of a major moment in gene therapy, and this new application in chronic pain is only the latest example.”

NYU Dentistry Wins STAT Madness 2023

A targeted gel to treat gum disease garnered the most votes in the bracketed competition

NYU Dentistry has won the STAT Madness 2023 competition, a virtual tournament celebrating recent breakthroughs in science and medicine. The NYU Dentistry research beat out 63 other studies from across the country, making it the first time that research from a dental school has won STAT Madness.

"We are so excited that our team’s innovative research has won this competition. It is a recognition of the importance of discoveries in oral health, as our research will provide an alternative treatment to the most prevalent oral disease," said Xin Li, professor of molecular pathobiology, who led the study with Deepak Saxena, Yuqi Guo, and Fangxi Xu, also of the Department of Molecular Pathobiology.

School Dental Program Prevents 80 Percent of Cavities with One-Time, Non-Invasive Treatment

Silver diamine fluoride, as well as sealants, protected against cavities in school-based program

In a study of nearly 3,000 children in kindergarten through third grade at 47 New York City schools, silver diamine fluoride — a liquid that is brushed onto the surface of teeth to prevent cavities or keep them from worsening — was as effective against cavities as dental sealants, the standard of care. A single dose of either topical treatment given in elementary schools prevented roughly 80% of cavities and kept 50% of cavities from worsening when children were seen two years later.

The findings, published in JAMA Network Open, offer an efficient and cost-effective approach to improving children’s oral health through school-based care.

In 2017, NYU Dentistry researchers received funding from the Patient-Centered Outcomes Research Institute (PICORI) to run the nation’s largest school-based cavity prevention study, which they named CariedAway.

“One CariedAway cavity prevention treatment, provided just before schools closed during the pandemic, was remarkably effective over the following two-year period,” said Richard Niederman, DMD, professor of epidemiology & health promotion, co-principal investigator of CariedAway, and the study’s senior author, who led the study with Ryan Richard Ruff, MPH, PhD, associate professor of epidemiology & health promotion, co-principal investigator of CariedAway, and the study’s first author.

Researchers Modify Drug to Enter Cells and Treat Pain

Altered version of anti-nausea drug netupitant reaches inside cells to disrupt signaling and provide sustained pain relief

Altering the chemical properties of an anti-nausea drug enables it to enter an interior compartment of the cell and provide long-lasting pain relief, according to a new study led by researchers at the NYU Pain Research Center. The study, published in the Proceedings of the National Academy of Sciences (PNAS), illustrates how pain signaling occurs inside cells rather than at the surface, highlighting the need for drugs that can reach receptors within cells.

“Sustained signaling in endosomes is necessary for the hyperexcitability of pain-sensing neurons involved in chronic pain,” said Nigel Bunnett, PhD, professor and chair of the Department of Molecular Pathobiology, associate dean for research, and the study’s senior author. “As a result, treating pain may require the development of drugs that penetrate cells, are retained in endosomes, and disrupt signaling inside the cell.”

Periodontal Inflammation Parallels Novel “Cytokine Score”

Higher levels of cytokines in saliva match greater periodontal inflammation

Researchers in the Ashman Department of Periodontology & Implant Dentistry have developed a single score to describe the level of cytokines in saliva, and this score is linked with the severity of clinical periodontal inflammation, according to a study published in the journal PLOS ONE.

In the PLOS ONE study, the researchers wanted to know if clinically detected gum inflammation could predict the level of cytokines in saliva. They found that PISA (Periodontal Inflamed Surface Area) scores were significantly associated with new cytokine scores, independent of other factors including age, gender, smoking, and body mass index (BMI). The higher a cytokine score, the greater the periodontal inflammation.

“While more research is needed to test the “cytokine score,” it could hold promise for measuring how well a patient responds to treatment for periodontal disease, predicting periodontal disease recurrence, or detecting ongoing inflammation related to systemic diseases, like cardiovascular disease, diabetes, and Alzheimer’s,” said Angela Kamer, DMD, MS, PhD, associate professor of periodontology & implant Dentistry and the study’s senior author.

Study coauthors included Vera Tang, DDS, MS, clinical assistant professor of periodontology & implant Dentistry (first author), and Leena Palomo, DDS, MSD, professor and chair of the Ashman Department of Periodontology & Implant Dentistry.

Dr. Timothy Bromage’s Research Highlighted in UN Report for the Year of Water

In advance of the 2023 United Nations Conference marking the “Year of Water,” the UN Secretary General has issued a report featuring a comprehensive water study that Timothy Bromage, PhD, professor of molecular pathobiology, and researchers at NYU Abu Dhabi conducted jointly with the Ministry of Natural Resources and Environment and the National University of Samoa from 2018 to 2020, at the request of the government of Samoa. The report, titled “The Biosecurity of Upolu Fresh and Salt Water Environment Water Resources,” can be viewed here, along with two scientific papers coauthored by Dr. Bromage that emerged from the study.

Study Conducted by Dr. Shulamite Huang Evaluates the Impact of Dental Office Closures During Covid-19 on Dental Conditions Among Children

The study concluded that lack of access to dental care during a time of significant health care system strain led to additional burden on hospital emergency departments

At the 2023 IADR meeting, Shulamite S. Huang, PhD, assistant professor of epidemiology & health promotion, presented findings from a study evaluating the impact of dental office closures due to the pandemic on the share of dental conditions on hospital emergency departments (EDs) among Medicaid/CHIP-eligible children. The study concluded that the lack of access to dental care during a time of significant health care system strain led to additional burden on EDs, and that future work is warranted to examine how to maintain dental care access during times of health care system strain.

NYU Dentistry Researchers Among Coauthors of Study That Reveals How Female Bones Permanently Change After Giving Birth

In a study that appeared in the journal PLOS ONE, researchers, including Timothy Bromage, PhD, professor of molecular pathobiology, and Dr. Bin Ju, adjunct assistant professor of molecular pathobiology, revealed that female bones permanently change after giving birth. The research, based on an analysis of primates, sheds new light on how giving birth can permanently change the body. The study was led by Paola Cerrito, PhD, whose doctoral thesis in anthropology was co-mentored by Dr. Bromage.