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Salivary Gland Has a Lot of Nerve

August 25, 2016

Sarah Knox
Sarah Knox's research focuses on the salivary gland. Photo by Elisabeth Fall

By Andy Evangelista

In the family of biological fluids, saliva is like a middle child: often underappreciated or taken for granted. You even call it “spit.”

But spit is a good thing, and oral health experts tout its importance. It lubricates your mouth, helps you swallow, protects teeth against bacteria and aids in the digestion of food.

Manabu Manandhar, a student researcher in Sarah Knox's lab, has combined two of his passions: research and dentistry. Read more

If you don’t have enough spit, life is miserable: massive tooth decay, infections and wounds in the mouth, constant thirst and inability to taste or even eat hot or hard foods. Those who can’t generate saliva don’t even get a good night’s sleep because they wake up often to rehydrate, and then are tired during the day.

Such is the case for some 4 million people in the United States — mostly women — with an autoimmune disorder called Sjögren's syndrome, which includes severe dry mouth as a symptom. It’s similar for those with throat and neck cancer – more than 60,000 diagnosed every year – because the radiotherapy that kills their cancer also destroys the salivary glands, stunting the flow of saliva.

Investigating the 'saliva factory'

Sarah Knox, a scientist in the School of Dentistry’s Department of Cell and Tissue Biology, focuses on the salivary gland – the saliva factory. Knox digs deep into the microscopic inner workings of this factory. She sees vibrant and healthy cells, but also those that are destroyed by the same radiation that kills tumor cells.

In particular, Knox explores the parasympathetic nerves, which diminish in supply and power when the salivary gland is zapped by radiation. “These nerves play a very significant role in tissue maintenance and continuous tissue repair over their lifetime.” 

Also, the parasympathetic nerves may be a target or avenue for treatment that would restore salivary gland function in people with head and neck cancer and immune disorders.

In Knox’s laboratory, researchers study biopsied salivary gland tissue from cancer patients to understand how tissue cells succumb to radiation. They also grow salivary glands from mice for in vivo studies of how the nerves trigger tissue regeneration.

“We want to hunt down the neuronal factors that promote regeneration,” said Knox. “Our goal is to find and identify molecules that we can use to regenerate patients’ salivary glands or create them anew. The idea is to return these unfortunate people to a quality of life they deserve.”

Far-reaching implications

Knox’s quest to understand fully how the salivary gland and its nerves function will have great value, far beyond oral health. By deciphering the mechanisms by which nerves communicate with tissue cells and, in particular, stem cells, her lab is answering some fundamental questions about how organs throughout the body form, grow and repair.

Every organ in the body, from the beginning of their development, is supplied with nerves, which regulate stem cells that are essential to organ architecture, repair and regeneration. Knox’s lab utilizes ex and in vivo experiments, mouse genetics, bioinformatics and human tissue samples to learn what controls stem cell behavior and how that influences organ and tissue formation and regeneration.

That research may offer a roadmap for therapies that could restore organ function in people with cancer, immune system disorders and diseases of aging. For example, one way to regenerate tissue may be to reactivate endogenous stem cells that remain in tissue even after the tissue is damaged. Knox’s lab, in its studies of throat and neck cancer patients with salivary gland dysfunction, hopes to identify molecules that perhaps can lead to novel drugs or alter nerve signaling systems to jump start those stem cells. The lab also is looking at how it may target genes involved in the replenishment of tissue.

“The body already harbors the tools we need to understand and create tissue repair,” she said.

In the UCSF tradition of collaboration and innovation, especially among basic scientists, Knox’s School of Dentistry laboratory connects with cancer researchers, immunologists, clinicians, geneticists and others at the Parnassus and Mission Bay campuses.

Her research training is as a bioengineer, but she understands that collaboration with scientists from many fields is needed to complete the blueprint of tissue and organ architecture and, thus, build therapies.

Like the nerve systems she studies, Knox is making the right connections.