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From Clinical to Lab
From the clinic to the lab
By JIM BISCO
Published: April 1, 2010
Salivary research was pioneered in UB’s Department of Oral Biology by its first chair, Solon (Art) Ellison, and then propelled into the modern technological era by Michael Levine, whose work influenced a generation of young researchers, among them Mira Edgerton.
“So many of us here now have been trained by Mike. He stressed the importance of getting involved in research in a substantial way,” she says today about her work with him in the 1980s. “At the time, salivary research was in its infancy, and it was exciting to be a part of that. For a dentist, it was very interesting because it was such a new area and people don’t really appreciate the importance of saliva to oral health.”
Edgerton, a research professor in the departments of Oral Biology and Restorative Dentistry, has been mining the rich potential of salivary research for more than 20 years. She has seen patients in the clinic who have lost saliva due to medications, chemotherapies and various other reasons. She has seen patients in her prosthodontics practice with Sjogren’s syndrome, an inflammatory disease that destroys salivary function.
“When you see what a severe problem it is to their oral health and sometimes even to their eating and swallowing and functioning, you appreciate the importance of saliva,” she says.
Edgerton says that her clinical practice gives her unique insights into patients with particular problems and the clinical issues that can be addressed in basic research. “In my research component here, I look at specific aspects of basic science and salivary research that could potentially benefit these patients at some point,” she says.
During her specialty training at UB in the 1980s, Edgerton recalls that the search for an effective salivary substitute was under way to help people afflicted with dry mouths. While the search continues for that elusive goal, the research focus, according to Edgerton, has narrowed.
“We didn’t really understand what the multitude of components were in saliva. Saliva has hundreds of proteins and most of them have their own distinct function and there are families of proteins with interrelated functions,” she observes. “I think where the field has evolved is to a better understanding of individual components and proteins in saliva and how we can enhance them.”
Edgerton began to explore salivary antimicrobial agents, specifically the histatin and defensin proteins that keep bacteria and yeast from overgrowing. Such overgrowth leads to oral candidiasis, an opportunistic disease in patients receiving cancer chemotherapy, AIDS patients, diabetics and in many elderly groups, especially those using oral prostheses.
“Histatin is sort of the innate immune in the salivary,” she explains, “then there is the host immune—two branches of immunity that we’re studying that prevent oral candidiasis. Sjogren’s patients have a lot of oral candidiasis because they lack the innate immune of the histatins and salivary components, whereas the HIV patients are missing another immune component.”
HIV-positive patients have been a particular focus—a population that develops high levels of this disease. For a long time the search was on for the missing immune component that predisposes these patients to the disease, lowering their CD4 cell levels.
Edgerton has collaborated with Sarah Gaffen, a former member of the UB oral biology department and now part of the University of Pittsburgh, in research that revealed why these patients are so susceptible to candidiasis—they lack a Th cell known as Th-17, a principle defense component required for immunity.
“We’re trying to develop the immune components for HIV patients who are Th-17 deficient,” she says. “If we understand the immune basis for the defect, then we can look at ways to modulate or replace or enhance what they’re missing in their immune system.
Edgerton’s hope is that salivary proteins can be used as therapeutics. “There still is not any good drug on the market now to treat oral candidiasis. It’s actually a very large problem. So we’re hoping that natural proteins will be therapeutic agents. Our ultimate goal is to come to a clinical chair-side application for this research.”
This goal reflects the new focus of the National Institutes of Health (NIH) on bringing basic research findings more quickly to clinical applications, according to Edgerton. “I think we’re seeing things on the horizon that will translate to clinic,” she says. “There’s an awfully big patient population that has bacterial yeast infections for which targeted peptide therapies will be very, very helpful. We’re getting close.”
Edgerton has received NIH funding for her research for the past 20 years. She recently received a grant through a provision of the American Recovery and Reinvestment Act that provides supplemental funding to explore areas beyond the focus of one’s research.
“Often when you’re doing research, you find really cool and interesting things that you’d like to pursue but are not directly what the main thrust of your work is,” she says. “The stimulus money funds that for you. In one of the fungal proteins that we looked at, we discovered that if the yeast are missing this protein, they can’t colonize in mice and they don’t have any infection properties. We never expected to find that. It was something we found in the course of looking at our histatin targets. So we submitted to the NIDCR (National Institute of Dental and Craniofacial Research) that we would like to see why is it essential for the yeast to colonize and become variable in this protein. It was a neat opportunity to go beyond what we initially planned with our various findings.”
Edgerton, who is director of the PhD program in oral biology, appreciates working with a wide variety of students, from undergraduates to post-graduates. “The really fun thing about being at a university dental school is to get students excited and involved with research, to look beyond what they see in clinic,” she says.
Edgerton has played an integral role in helping to build what is recognized as an internationally recognized oral biology department. “We’ve recruited a lot of younger, new people in the department that have great careers ahead of them,” she says. “Oral biology is a great place to be as a researcher. It’s a really collegial department with lots of exchange of ideas.”
Her career path was a far cry from when she started out in college (Ohio State) as a music performance major, a violinist. “I decided that it was probably going to be too tough a lifestyle and career, so I went back to the sciences,” she recalls. “Dentistry just seemed to be an interesting area that combined science, research and medicine. So I came to it in a roundabout way and never regretted it for a minute. It’s a terrific career. Everyone should have so much fun. It’s the spectrum of things that I really like.”
Edgerton is married to Kenneth McHenry, associate professor in the Department of Restorative Dentistry, whom she met at UB. Does this result in shop talk across the dinner table? “We talk more about the people in dentistry,” she says. “Things like ‘I have this really interesting patient’ or ‘I had an interesting talk with a student.’”