UB oral biology and biochemistry professors receive NIH grant to study salivary gland regeneration

BUFFALO, N.Y. ­— Salivary glands are essential for everyday human functions —speaking, swallowing, tasting and protecting the mouth—yet they do not fully recover once they are significantly damaged.

“Patients who undergo radiation therapy for head and neck cancer, live with autoimmune conditions such as Sjögren’s disease, take certain medications, or simply experience age-related decline can develop chronic dry mouth that affects eating, swallowing, oral health, sleep, and overall quality of life,” says Rose-Anne Romano, PhD, associate professor of oral biology in the University at Buffalo School of Dental Medicine.

An estimated 20% of people around the world are affected to some degree by salivary gland disorders.

“Medication use—especially in older adults—is one of the most widespread contributors,” Romano says. “Overall, salivary gland dysfunction represents a significant and often underrecognized global health burden.”

Romano recently received a two-year, $440,275 grant from the National Institute of Dental and Craniofacial Research to explore how salivary glands repair and regenerate after injury. The co-primary investigator is Satrajit Sinha, PhD, professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences.

Sinha, whose specialty is gene expression, genomics and epigenomics, has had long-term collaborations with Romano and others in the dental school. He says they share common research interests and expertise for using oral tissues as a valuable model system.

The two researchers are bringing their expertise together to solve what has seemed like an intractable problem.

“Despite the clear clinical need,” Romano says, “we still do not fully understand how salivary glands maintain their normal physiological function and secrete saliva as and when needed upon the right stimulus.”

The funding for this study will allow them to investigate how the stem cells of the salivary glands facilitate recovery and regeneration of the organ after damage or disease to ensure proper saliva production and other functions, Sinha explains.

“We will also draw knowledge insights from other tissues and organs where similar regrowth and repair take place,” Sinha says. “Once this study is completed, we should be able to identify and have a better understanding of the key molecular cogs in the cellular machinery that facilitate the healing process.”

Understanding roles of specific genes

When an organ such as a salivary gland gets damaged, stem and progenitor cells help rebuild it. In the ideal scenario, these cells can replicate, decide what kind of cell they should become and grow into a fully working tissue with restored function.

“These decisions are controlled by networks of genes and signaling pathways that must turn on and off at the right time,” Romano says.

In prior studies, Romano, Sinha and other oral biology researchers have used genomic and epigenomic data to decode salivary gland identity and the molecular blueprints of tissue homeostasis and regeneration. These studies led them to discover a gene called Six1, which likely plays a key role in these processes.

To follow up on these observations, Romano and Sinha will study what happens when Six1 is selectively turned off in a mouse model. This approach will allow them to determine how essential Six1 is for proper regeneration of the tissue.

“We will examine specific cell populations to see which ones participate in repair, how they change over time and how their gene activity is regulated,” Romano says. “We will also explore how Six1 influences the way genes are switched on and off and how the cell’s epigenomic landscape shifts and adapts during recovery.”

Findings could help suffering patients with gland dysfunction

In the long term, this study will allow them to submit a larger multiyear NIH grant proposal where they can follow up and validate these findings, Sinha says.

“The hope is to generate a clearer and more complete picture of how salivary glands regenerate after injury, which will ultimately inform new strategies to restore gland function in patients suffering from chronic dry mouth and salivary gland dysfunction,” Romano says. “Ultimately, this knowledge could help us design new treatments to restore salivary gland function in people affected by conditions such as autoimmune disease, radiation therapy for head and neck cancer, medication side effects and aging.”

The National Institute Of Dental & Craniofacial Research of the National Institutes of Health under Award Number R21DE035609 supported the research reported in this publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.