Periodontics Professor Studying Saliva to Improve Quality of Life, Prevent Cancer
By David Enders
As bodily fluids go, saliva tends to be underestimated. In truth, it is far too valuable to waste spitting on the ground. Think of it as a noble sentry posted at the gateway to your entire digestive and respiratory system.
We take saliva for granted, but we shouldn’t have to go without it to appreciate its many wonders. In Sjogren’s syndrome, an autoimmune disorder that destroys the salivary glands, too many patients are forced to do just that. Without the ability to produce saliva, they must drink water every 10 to 15 minutes, they have difficulty eating and speaking, and their teeth deteriorate due to increased bacteria levels and lack of mineralization. Bacteria can build up and lead to other health conditions. Some 30 percent to 40 percent of Sjogren’s patients will get B cell lymphoma in the later stages of life due to changes caused by their hyperactive immune system. The disease is often manageable but incurable. Similarly, patients who undergo radiation therapy for oral cancer lose the salivary glands and have significant decrease in their quality of life.
Brij B. Singh, PhD, associate dean for research and professor of periodontics in the School of Dentistry at UT Health San Antonio, is working to change all that. After 20 years of multi-disciplined research on salivary gland function, he believes epigenetics may hold the key to reversing the condition. Dr. Singh is the primary investigator on a five-year $1.65 million grant from the U.S. Department of Health and Human Services and the National Institutes of Health (NIH) to uncover the role of epigenetic regulation in Sjogren’s syndrome.
He also has a grant for the past 20 years through NIH that deals with the mechanism of saliva secretion. This funding was just renewed this year for $2.7 million. In addition, he also received a Translational STARs (Science and Technology Acquisition and Retention) Award with a $500,000 grant from the UT System. The award was created in an effort to recruit and retain nationally recognized research leaders.
“Sjogren’s primarily affects females. More than 90 percent of cases are females over 40 years of age,” Dr. Singh explains. He suspects epigenetic changes to the 23rd chromosome may be responsible for this gender bias. Females have two X chromosomes on the 23rd pairing, and one of these two chromosomes is randomly turned off early on in cellular development. Males always have one X chromosome from their mother and one Y chromosome from their father. This means, in any given cell, a woman can express genes from the X chromosome contributed by her mother or her father. Since the X chromosome expresses far more genes than the Y, this gives her more cellular diversity than men leading to more developmental options and more ways to prevent disease.
The X chromosome is also the location of hundreds of genes that control our immune system. Dr. Singh suspects the same random X-chromosome inactivation (XCI) that increases female cellular diversity can, in rare conditions, go awry and trigger autoimmune diseases. “Our hypothesis is that in Sjogren’s syndrome epigenetic changes are happening in a way that the X chromosome which is inactivated is not completely inhibited and allows some of its genes to pass through and cause disease formation.”
Your epigenome determines how your genes are used and is greatly impacted by your unique biological environment. “As we age, our DNA is not so tightly controlled and starts to loosen up, and this can cause problems. In addition, when we get bacterial and viral infections, this also can alter our epigenome.” In Sjogren’s, epigenetic changes can stimulate the immune system to overproduce “T and B cells” that can overreact to signals and destroy the salivary glands. Poorly regulated activation of these T and B cells is associated with a variety of autoimmune disorders. This is why Sjogren’s often appears alongside other autoimmune disorders such as lupus and rheumatoid arthritis.
Many drugs that work on other autoimmune disorders have not had an impact on Sjogren’s, because they do not deactivate the underlying mechanism. A solution may not come easily, but it will come, Dr. Singh predicts. “Once we thoroughly understand the physiology, drug development will come. When we sequenced the human genome, the understanding back then was that this would help us understand many diseases and cure them, but this was never the case. In humans, the number of genes that code proteins is less than 2 percent of the entire genome, and the other 95 percent to 98 percent is all noncoding DNA and has other physiological and regulatory functions, and now we are in the process of trying to understand those functions.”
As research advances, Dr. Singh believes it is the responsibility of researchers to help manage Sjogren’s to improve quality of life. His research on calcium channels and stem cells could play a part. Calcium channels play a key role in the amazing ability of stem cells to efficiently migrate to damaged tissues and begin rebuilding. This unique ability may eventually help regenerate salivary gland cells damaged by Sjogren’s or by radiation therapy. “In radiation therapy, the first thing that normally goes bad is the salivary glands.”
As the associate dean for research, Dr. Singh is responsible for the school’s research goals, including contributing to the broad body of basic and applied knowledge related to oral health. “Our dental research faculty has done tremendously well. We have been able to generate nearly $10 million a year in funding for the past few years which is remarkable for a faculty of about 35 individuals. My goal is to maintain this level and increase it as much as possible to bring in more researchers, to look in new areas, and to push our efforts to meet the needs of our diverse populations in South Texas.”
Outside of research, Dr. Singh admits he never seems to have much spare time. But when he does, he enjoys spending time traveling with his family and indulging a guilty pleasure of reading medical fiction. “You can imagine something completely different and maybe think of new approaches to old problems.” A new approach may finally give saliva the respect it deserves.