Periodontitis (gum disease) is one of the most common causes of tooth loss in adults. Dr Mandeep Ghuman is interested in why gum tissues normally do not fully heal themselves following treatment of the disease, and he has spent his research career exploring the cells, and the molecules they release, that could be manipulated to promote tissue regeneration.

Mandeep trained as a dentist at Queen Mary, University of London. As part of his studies, he transferred to King’s for a year to complete his intercalated BSc, conducting a research project in oral microbiology. “Looking back that's where I got the inspiration to pursue a clinical academic career,” Mandeep said. “I was always interested in the more fundamental biological aspects of dentistry. However, when I graduated, I went into practice and thought I would just be a regular dentist.”

Mandeep quickly realised that working in a dental practice wasn’t for him, so he went back into hospital to complete some more clinical training. “Ultimately, I realised what I was really hankering for was to do more research,” he said. “So, I spontaneously emailed a couple of professors who were working in fields that interested me. One of them, Professor Francis Hughes, responded.”

Mandeep met with Professor Hughes on a monthly basis for a year to develop a research proposal. He ended up resigning from his surgical job and working in Professor Hughes’ lab on a visiting basis, gathering some pilot data and getting laboratory research experience. This paid off; Mandeep secured a Clinical Research Training Fellowship with the Medical Research Council (MRC), which allowed him to complete a PhD.

At the time, Mandeep was interested in bone biology. Patients with gum disease progressively lose part of their jawbone that supports the teeth, which cannot be grown back. For his PhD project, Mandeep explored whether the cells of the gums overlying the bone holding the teeth might inhibit bone from reforming once lost. Using cell culture approaches, he found that inhibitors to bone forming proteins were released by the gum cells and reduced bone forming activity of bone cells.

After his PhD, Mandeep was employed as a research fellow with Professor Hughes. He secured an NIHR-funded Clinical Lectureship, allowing him to carry out his specialist training in periodontology alongside some protected research time. He also started second supervising some of Professor Hughes’ PhD students. For his postdoctoral work, Mandeep began to focus on stem cells, a special group of cells that exist in many adult tissues and have the potential to renew and replace damaged cells. At the time, stem cells were becoming better described, particularly in the dental tissues. Mandeep therefore began exploring how periodontal stem cells might be influencing their neighbouring cells, potentially affecting tissue regeneration in the mouth.

Today, Mandeep continues to research aspects of regenerative cell biology with regards to the periodontal tissues. His group are now exploring the factors that periodontal cells release in small, membrane-bound packages called extracellular vesicles. He is taking a comparative approach, assessing the differences between oral tissues and skin. “If we cut our skin badly as adults, we tend to scar,” Mandeep explained. “But one of the great things about working as a dentist, particularly as a periodontist, is that you can do quite a lot of surgery in the mouth and the healing potential there is very good. To understand why the mouth is so good at avoiding scar formation, we’re comparing the factors released by the skin cells and the oral cells. The aim is to identify unique secretions from the oral cells that could potentially be applied to reduce scar formation outside the mouth.”

Mandeep is also analysing diseased gum tissue to explore its potential for regeneration. “Patients with advanced gum disease may require surgery, which involves removing the diseased tissue. Some of these patients are kind enough to donate their tissue samples to us, which allows us to analyse the microbiome of the diseased gum and to determine which genes are being expressed by the periodontal cells. We hope to identify therapeutic opportunities to manipulate the tissue to grow and heal. Currently, dentists discard this diseased tissue after surgery, but there is some evidence that it might have some healing or regenerative capacity. If there's a way of manipulating it, that might be better for the patient than throwing it away.”

Mandeep has remained focused on tissue regeneration while shifting his system of choice from bone to stem cells and cell secretions. “I think some of it was about trying to catch the zeitgeist,” he explained. “There are trends in research that come and go. Some of this is due to technological capability, because previously we didn’t have the molecular or analytical tools to answer the questions we really want to address. So, we put these on hold until the next technological advance, which might allow us to start exploring these new areas. In dental research, we sometimes have to wait a few years for these techniques to become more cost effective for us; unlike some areas of medical research, it can be tricky for those in dental research to attract a grant that will be able to cover those sorts of technical expenses.”

Looking to the future, Mandeep emphasises the need for clinical academics to keep abreast of the latest developments in research. “I think technological developments are a big factor in determining direction of research,” he said. “The advent of AI and machine learning will affect all our careers, especially those of our younger colleagues. It’s going to have a profound influence in all areas of life, including research. If you're not becoming familiar and engage with it, I think you could get left behind.”