Understanding diabetes and oral health

Despite a robust amount of research about diabetes, much is still unknown about its effects on oral health. Changes in inflammation are understood to contribute to the impact of diabetes, but what is driving the increase is less clear.

Through a study in the Graves Lab, led by Dana Graves, a professor of periodontics in the School of Dental Medicine, the goal has been to identify molecules that are modulated by diabetes to increase pathology.

One project, co-led by research scholar Hamideh Afzali, used single-cell RNA sequencing, which is a sophisticated assay that measures the mRNA level of thousands of genes in each individual cell. The sequencing focused on white blood cells in contrast to many wound healing studies that focus on fibroblasts. That led the research team to identify the gene S100A11 that was found at high levels in diabetic wounds in a specific white blood cell, neutrophils.

"Not as many genes were obviously affected by diabetes as we expected"," explains Graves. "There's not a huge number that are different. … And this gene is the one that Hamideh thought was pretty important."

The process was to examine the healing of a diabetic wounds in mice and conduct bioinformatic analysis during the healing process when connective tissue starts to form. The analysis led to S100A11, but the question remained whether inhibiting this gene would improve healing.

Helpful in this process was Sanan Gueyikian, a third-year neuroscience major with a minor in health care management in the College of Arts and Sciences, who measured histologic tissues to assess, quantitatively, whether healing improved. Gueyikian conducted this work through the Penn Undergraduate Research Mentoring Program (PURM), a 10-week opportunity from the Center for Undergraduate Research and Fellowships. The program provides rising second- and third-year students with a $5,000 award to work alongside Penn faculty.

"There's a long history of diabetes in my family, and the lack of information regarding its cause or what it can trigger fascinates me," Gueyikian says. "I am also interested in dental medicine and pursuing it in the future. So, Dr. Graves' lab was the perfect place for me to explore these interests."

Through the experience, she says, she learned a lot about signaling pathways and testing for genes. Gueyikian adds that, with the mentorship of Afzali, she learned to read research papers differently and understand them better. She says that this was her first experience with research and further cemented her interest in oral surgery.

"I came out with a much better understanding of the research process," she says.

A second research project in the Graves Lab, supported with a PURM student researcher, looked at periodontal disease and bone loss among diabetics. Su Ah Kim, a third-year student majoring in finance and healthcare management at the Wharton School with a minor in chemistry, worked with senior research investigator Min Liu to genotype and quantify bone loss in diabetic mice. Liu says Kim is "very smart and works very hard and learns very fast," and analyzed the bone levels to help determine whether the Akt1 gene played a significant role in the increased periodontal disease caused by diabetes.

Like Gueyikian, Kim says her family has a history of diabetes, which partly spurred her interest in the PURM project. She plans to pursue dentistry after graduating and has spent time shadowing at University Dental Associates. She hopes to combine her business and dentistry knowledge to one day own her own practice.

The research opportunity, Kim says, taught her how to be more self-sufficient, while also giving her a chance to interact with Penn Dental students who were happy to answer questions about dentistry as a career path.

"I learned in the 10 weeks that self-initiation and being proactive are fundamental for success in scientific research," Kim says.

"It was my first time conducting research in a wet lab, so I experienced learning curves with performing procedures, including genotyping and histological staining," she adds. "However, through several processes of trial and error and collaboration with other lab members, I developed a strong knowledge of each procedure, which I was able to carry out successfully on my own."

Graves is a big fan of the PURM program and has brought undergraduates into projects for many years, he says-always to great success.

"Both of them contributed a lot to their projects," says Graves. "This was not a teaching exercise; this was an opportunity to participate as a researcher. They both will be coauthors on a paper and both provided valuable data, bringing a lot of enthusiasm, while learning quickly. They were a pleasure to work with."

Participating PURM students, Sanan and Kim, he says, learned how important teamwork is in a research lab setting and how it is necessary to obtain successful results. He says both students embraced a spirit of cooperation, which is "a key factor" in lab work.

"They became real researchers toward the end, both understanding their projects well and capable of carrying out the experimental assays," he says.

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