UB oral biology researchers receive combined $6.6 million in grants

Researchers in the Department of Oral Biology were recently awarded six grants totaling $6.6 million, helping to double funding received by the department in the previous year.

The grants, awarded by the National Institutes of Health, will fund investigations that aim to better understand the bacteria behind periodontal disease, examine the influence of white blood cells on Sjögren’s syndrome and explore the effects of a key protein on bone loss.

UB’s Department of Oral Biology is also one of just three institutions across the nation to receive a training grant from the National Institute of Dental and Craniofacial Research (NIDCR) to develop the next generation of leaders in oral biology research.

The new research projects will be led by Keith L. Kirkwood, professor; Michelle Visser, assistant professor; and Jill M. Kramer, assistant professor.

“Years of investments in the department are bearing fruit,” says Frank A. Scannapieco, professor and chair of the Department of Oral Biology and associate dean for faculty and professional development in the School of Dental Medicine.

“We have built a critical mass of high-quality people that are becoming successful or continuing to be successful. Ours is one of the most productive departments of oral biology in the country.”

The training program and research projects:

The absence of tristetraprolin (TTP), a protein critical to the control of inflammation, leads to rapid and severe bone loss, UB researchers recently discovered.

Now, with the support of a five-year, $2 million grant from the NIDCR, a team led by Kirkwood will investigate how the protein affects the breakdown and reabsorption of bone with age. 

Inflammation is a necessary reaction by the immune system to protect the body from injury or infection, but if not controlled, it can lead to the destruction of bone and prevention of bone formation.

While TTP is known to play a major role in the regulation of inflammation, its production slows with age. The research results could have a profound impact on the management of bone health in the elderly, a population at higher risk of osteoporosis and periodontitis, a disease affecting 70 percent of adults age 65 and older, according to the Centers for Disease Control and Prevention.

Insights from the study could also aid development of medication that elevates TTP levels, promoting healthy aging of bone.

Additional investigators include Bruce Troen, professor and chief of the Division of Geriatrics and Palliative Medicine; Kenneth Seldeen, research assistant professor; and Ramkumar Thiyagarajan, research associate, all in the Jacobs School of Medicine and Biomedical Sciences at UB.

The investigative team also includes Perry Blackshear, senior investigator at the National Institute of Environmental Health Sciences, and Lixia Zhang, research scientist in the UB Department of Oral Biology.

UB researchers received a five-year, $1.9 million award from the NIDCR to explore the role oral spirochetes, a group of bacteria found in dental plaque, play in periodontal disease, inflammation and other illnesses.

The research, led by Visser, will examine how a protein released by the bacteria can impair neutrophils, prominent white blood cells of the immune system that serve as the body’s first responders after infection.

The pathogenic protein, called major outer sheath protein, disrupts the neutrophils’ signaling pathways, preventing the cells from migrating to bacterial infections and beginning the process of inflammation.

The proteins play a key role in bacterial survival in periodontitis, a gum infection that affects nearly 50 percent of people in the United States in some form, says Visser.

Developing a stronger understanding of major outer sheath proteins will help researchers build therapeutic antibodies that prevent neutrophil disruption and improve oral health. The research will also survey proteins from comparable bacteria to determine if they function similarly.

Additional investigators, all from UB, include Joseph Balthasar, professor and associate dean for research, and Jun Qu, professor, both in the School of Pharmacy and Pharmaceutical Sciences; Gregory Wilding, professor and chair of the Department of Biostatistics in the School of Public Health and Health Professions; and Ashu Sharma, professor in the Department of Oral Biology.

The Department of Oral Biology is one of three institutions nationwide to receive a training grant from the NIDCR to help train the next generation of dental scientists engaged in oral health research.

The five-year, $1.5 million award will fund the Buffalo Oral-Research and Specialty Training (BORST) Program, which provides stipend and tuition support to dentists interested in pursuing both clinical specialty and doctoral research training.

By training future leaders in dentistry, the award will help address the critical need for well-trained investigators in dental, oral and craniofacial research.

BORST scholars will complete clinical residencies in periodontology, oral pathology or orthodontics. The program will also provide career development, mentorship and research training opportunities in oral health, craniofacial biology and bioengineering. Areas of research focus include immunology, oral pathogens and systematic disease, saliva, microbial pathogens, bone and tissue engineering, and clinical and translational research.

Kirkwood, principle investigator on the grant, will serve as BORST program director. Scannapieco is a co-investigator and program co-director.

B cells, one form of white blood cells, are a crucial component of the immune system that protect against infection. They also play a role in autoimmune diseases. Researchers have long known that B cells are altered in patients with Sjögren’s syndrome, but the precise way in which these cells affect the disease is not well understood. 

New research led by Kramer aims to understand how B cells become activated in Sjögren’s syndrome, and how an antibody called IgM that is secreted by B cells contributes to the disease.

Supported by a two-year, $319,000 grant from the NIDCR, Kramer will investigate IgM antibodies in the salivary glands of mice with Sjögren’s syndrome, an incurable disorder in which the body’s white blood cells attack healthy cells that produce saliva and tears.

Affecting more than 1 million Americans, 90 percent of whom are women, the disorder is characterized by dryness of the eyes and mouth, placing patients at a high risk for tooth decay and creating difficulties with talking and swallowing food.

IgM functions as the body’s garbage man, helping to clean up cellular debris and reduce inflammation before a stronger autoimmune response is triggered, says Kramer. But in a previous study, she learned the IgM found in the salivary glands of mice with Sjögren’s syndrome possessed distinctive characteristics making it more reactive to its body’s own cells.

By testing how IgM affects salivary function in mice, Kramer can learn whether the antibody’s presence in these glands is helpful, and if it could aid development of medicine and other treatments.

Additional investigators include Rose-Anne Romano, assistant professor in the Department of Oral Biology, and Guan Yu, assistant professor in the Department of Biostatistics.

In a separate two-year, $431,000 grant from the NIDCR, Kramer will examine B cell activation in Sjögren’s syndrome.

B cells are typically activated by bacteria and viruses. Research on autoimmune diseases has revealed that molecules produced by tissue damage also drive B cell activation; however, this has not been studied in Sjögren’s syndrome. Kramer will investigate if B cells from patients with Sjögren’s syndrome are hyper-responsive to these molecules.

The research may lay the groundwork for potential therapeutics targeting B cell activation through the damage-associated molecules, diminishing autoantibody production in Sjögren’s syndrome patients.

Yu is a co-investigator.

Kirkwood also received a two-year, $479,000 grant from the NIDCR to study the differences in immune system responses to periodontal pathogens between men and women.

The research will examine the effect of MKP-1, an enzyme that limits immune responses on cytokines and chemokines, which are proteins released by the immune system that promote inflammation. Researchers will also determine if DUSP1, the gene behind the enzyme, is silenced in periodontal disease tissue.

Understanding how these proteins are targeted may allow scientists to modify their expression for therapeutic benefits and create new possibilities for personalized treatment of periodontal disease.

Additional investigators include Zhang, research scientist in the Department of Oral Biology.