Dr. Brian Foster: Improving Lives Through Research
Brian Foster, PhD, Assistant Professor in the Division of Biosciences, has been at the College of Dentistry just four years, but he has already won two major research awards from the college: Paper of the Year in the basic science category in 2018 and Paper of the Year in the clinical science category in 2019. We recently caught up with Dr. Foster to learn about his award-winning work—and his ongoing quest to improve people’s lives through research.
Why are you passionate about research?
In a broad sense, you realize there are these questions about the world and how things work—in my case about biology and the development of teeth—and there are these fundamental questions that haven’t been answered. It’s really exciting to think about what experiments I can do, what new models I can develop and what new technologies I can use to answer those questions.
You’ve won Paper of the Year Awards for both basic and clinical science. Why is it important to you to explore both of these areas?
Probably 90 percent or more of what I do is basic science—growing cells in the lab, using mouse models which are a few steps removed from human biology—so when I have a chance to do something with clinical science, I really enjoy it. When I think about my research in the big picture, I’m trying to work on projects that will someday help us to prevent diseases and have a real clinical impact.
Tell us about your research on hypophosphatasia (HPP). What is HPP and what kinds of problems does it cause?
HPP is an inherited disease that causes a defective mineralization of the bones, which can be lethal, especially in infants. The most common dental problem it causes is premature tooth loss due to absence or reduction of cementum on the tooth root, causing a poor attachment of the tooth to the surrounding periodontal ligament and alveolar bone.
The most recent estimate is that one in 6,000 people have mild or moderate HPP.
One of your award-winning papers is about the new mouse model you developed for HPP research. How did your discovery help advance the study of this disease?
There was a model used for many years that really only captured the most severe type of HPP. It was very helpful—there have been more than 50 papers on it by now—but what we’ve realized is with this model, the mice couldn’t live past more than two to three weeks. We were imagining how we can help HPP patients who are 10 or 20 years old, and this mouse model was not surviving long enough to look at how HPP affects teeth at equivalent ages. We also knew a therapy was being developed to replace the defective enzyme in HPP with one that gets that enzyme level up and functioning to improve patients’ bones. In order to provide insights into HPP-associated dental problems and the ability of therapy to reverse and reduce these problems, we helped develop a new mouse model that allows mice to live longer with a less severe form of HPP.
Your other award-winning paper is about generalized arterial calcification in infancy (GACI), which impacts infants. Tell us about that and the dangers it poses.
GACI is caused by mutations in the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) gene that encodes a protein of the same name, and it almost always strikes in infancy immediately after birth. In a lot of ways, GACI is the opposite of HPP. In HPP, the molecule pyrophosphate accumulates and blocks proper bone and tooth mineralization—but in GACI it’s the opposite problem, with inappropriate calcification in soft tissue like blood vessels that causes severe hypertension and possible blood vessel ruptures. It’s a very rare disease, with only about 200 cases diagnosed to date.
And what did your research find?
We found in both a mouse model of GACI and in the very first study of dental manifestations of GACI in humans that tooth root cementum becomes dramatically thicker—about four times more than normal. This is interesting because it confirms that cementum formation is extremely sensitive to pyrophosphate levels (either increased in HPP or decreased in GACI), suggesting that modulating pyrophosphate levels is a central and fundamental mechanism directing the amount of cementum formation, and this has probably been evolutionarily honed over many millions of years since it is a shared mechanism between humans and mice.
What’s it like working with students on research projects?
I have two PhD students in my lab right now, various dental and dental hygiene students and some residents specializing in different areas of dentistry. I remember when I was a student, I had no clue how to write a paper or what experiments to do. Part of the job of a researcher is training the next generation, mentoring them and showing them the right way to do things—not just experiments, but also ethically.