Early career oral biology researchers receive NIH funding for disease-oriented projects

BUFFALO, N.Y. —  Zhibin Cui, DDS, PhD, and Harim Tavares dos Santos, DDS, PhD, joined the Department of Oral Biology in the University at Buffalo School of Dental Medicine in fall 2024 as promising research trailblazers.

And their promise is already coming to fruition. The National Institutes of Health recently awarded each of them a two-year, $320,000 grant for separate projects. Cui is studying the connection between a gene mutation and an aggressive form of oral cancer while Tavares dos Santos is studying a rare cell’s effect on salivary gland disorders.

“We were excited to hire Dr. Cui and Dr. Tavares dos Santos because of the research acumen they bring,” says Stefan Ruhl, DDS, PhD, professor and chair of the Department of Oral Biology. “Their contributions are enhancing the cutting-edge research that is a hallmark of the oral biology department and the dental school as a whole.”

Keith Kirkwood, DDS, PhD, Centennial Endowed Professor in the Department of Oral Biology and senior associate dean for research, notes that receiving simultaneous two-year RO3 grants, which can lead to larger grants, is impressive and speaks to the important work Cui and Tavares dos Santos are pursuing.

Cui, an assistant professor, is exploring whether oral squamous cell carcinoma, a tongue cancer linked to smoking, could be caused by two gene mutations, HRAS and CASP8. This form of cancer is highly aggressive; more than half the patients don’t survive five years past diagnosis.

Previous research has shown that CASP8 mutations could occur relatively early on, sometimes in a precancerous oral lesion. Thus, catching the cancer early is of paramount importance, and this research could pave the way toward that goal.

Formerly an assistant professor in the Department of Otolaryngology-Head and Neck Surgery at the University of California, San Francisco, Cui has studied these genes for years and has published two papers on this gene mutation.

CASP8, he explains, helps control how abnormal cells die and how tissue responds to inflammation. HRAS helps regulate when cells grow and divide, but when HRAS is mutated, it can become stuck in an “on” state, causing cells to keep multiplying.

His study examines whether CASP8 mutations remove an important protective brake, allowing HRAS-mutant oral cells to progress toward cancer more easily.

 “When we go back to the clinical data, we realized that the CASP8 gene mutation always co-occurs with the HRAS gene mutation,” he says. “So, we want to explore this further.”

Cui and his research team are testing the double mutation in transgenic mice to observe whether a tumor develops over several months.

“Eventually,” he adds, “we would like to develop a diagnostic marker for benign oral lesions that will transform to cancers and identify new treatment approaches for this cancer subgroup.”

Tavares dos Santos, also an assistant professor, is exploring whether a rare cell, called tuft, shapes stable salivary glands or contributes to salivary gland disorders. Tuft cells affect Sjögren’s disease, an autoimmune condition that eradicates moisture from the salivary gland, which results in difficulty talking and swallowing.

“Tufts are like tiny environmental sensors. They release chemical signals that communicate with other cells and help the tissue respond to changes in its environment,” said Tavares dos Santos, who began studying tuft cells while working as a postdoctoral fellow at the University of Missouri. He published a paper in the Journal of Histochemistry & Cytochemistry in 2022 showing that tuft cells are present in the salivary glands of mice, pigs and humans.

“But in other organs, we know that tuft cells can change in number and activity during inflammatory diseases,” he explains.

His research explores what the specific function of these cells are in a healthy salivary gland and whether they are related to salivary diseases, including Sjögren’s disease.

In the preliminary data that Tavares dos Santos and his team has gathered, it appears that tuft cell numbers change in Sjögren’s disease.

“Our main question is: Are the tuft cells the cause of the disease or just a consequence?” he says.

Along with studying mouse models, Tavares dos Santos and his team are collaborating with Saurin Popat, a head and neck surgeon at Sisters of Charity Hospital in Buffalo, to study human samples.

“If we determine that these tuft cells are involved with the initiation, progression, or perpetuation of Sjögren’s disease, they could be definitely targeted for treatment drugs,” he says. “What we want to know at this moment is: What are the receptors? What is on the surface of the cells that could be targeted?”

Tavares dos Santos notes that he’s grateful for the support of the oral biology department.

 “Every door that I knocked on with a question has been welcomely opened,” he says. “I hope to build a career here and reach my ultimate goal, which is to help people who have Sjögren’s disease and also to expand my lines of research.”