Former NIDCR directors and current researchers reflect on scientific milestones
During World War II, rampant tooth decay disqualified nearly 20% of military recruits from service. To address this issue, President Harry Truman signed legislation on June 24, 1948, to create what would eventually become the National Institute of Dental and Craniofacial Research. The institute is celebrating its anniversary throughout the year by highlighting its past accomplishments and presenting its vision for the future.
NIDCR began its slate of 75th anniversary events on March 17, 2023, with a symposium called “Scientific Strides of the NIDCR: 75 Years and Beyond,” held at the annual conference of the American Association for Dental, Oral, and Craniofacial Research (AADOCR) in Portland, Oregon. The symposium featured remarks and a Q&A session with three former NIDCR directors — Harold Slavkin, D.D.S., Lawrence Tabak, D.D.S., Ph.D., and Martha Somerman, D.D.S., Ph.D. — and its current director, Rena D’Souza, D.D.S., Ph.D., M.S. All three former NIDCR directors highlighted the importance of active, synergistic collaborations within the institute, across NIH, and with the broader research community.
Dr. D’Souza noted that the pandemic revealed the need to stay flexible as an institute to meet unforeseen challenges. She also highlighted the importance of putting patients at the center of every phase along the research continuum. “The best science is an inclusive activity” in which researchers engage with and seek to benefit patients and communities as they design, conduct, and share their work, she said.
Next, six of NIDCR’s current intramural investigators took the stage to highlight their research advances and share their visions for the future. Their presentations displayed the scope of NIDCR research, from molecular-level basic science, through translational work, to clinical studies. The intramural investigators were Marian Young, Ph.D., Pamela Robey, Ph.D., John (“Jay”) Chiorini, Ph.D., Niki Moutsopoulos, D.D.S., Ph.D., Ashok Kulkarni, Ph.D., and Janice Lee, D.D.S., M.D.
Dr. Young is NIDCR’s Deputy Scientific Director and a Senior Investigator in the Molecular Biology of Bones and Teeth Section. Her work into the formation of mineralized tissues expands on studies begun 50 years ago by her former mentor, John Termine, Ph.D. Research in this area has the potential to significantly impact the fields of tissue engineering and regenerative medicine. While the question of how bones form might initially seem simple, decades of research have shown that the intricacies of the process are difficult to tease apart. To demonstrate this complexity, Dr. Young described a specific gene that has opposing effects under different local conditions. In some parts of the body, the gene causes low bone mass, while in an adjacent tendon, it might trigger the production of bone. Dr. Young’s team aims to understand which instructions the body follows in each situation. That knowledge might reveal ways to ameliorate specific musculoskeletal diseases. As Dr. Young put it, “You have to figure out how things work before you can figure out how to fix them.”
Next, Dr. Robey, a Senior Investigator in NIDCR’s Skeletal Biology Section, highlighted the role played by specialized bone marrow fibroblastic cells in building and dismantling bone. Fibroblasts secrete proteins that help construct and maintain the structural framework of tissues. Dr. Robey is interested in the role these cells play in replacing and re-growing tissues that have been lost to disease or injury. Animals such as salamanders and starfish can easily re-grow lost limbs, but this regenerative ability is severely limited in humans. Much of Dr. Robey’s work involves developing animal models to study bone and cartilage defects and characterizing the various cell types that might function as tools for regenerating human tissue. The cells found in dental tissues are similar but not identical. She is especially keen to see a particular type of regeneration. “Maybe at some point we can build a tooth,” she said, optimistically. “That would be my goal.”
The next speaker, Dr. Chiorini, highlighted another area in which NIDCR has been a long-term leader — gene therapy. Dr. Chiorini is NIDCR’s Associate Scientific Director for Scientific Resources and Chief of the Adeno-Associated Virus Biology Section. He described gene therapy as “a concept that has been around since we discovered that DNA was the hereditary material.” At NIDCR, the emphasis has been on therapies for unmet clinical needs in the oral cavity. Specifically, Dr. Chiorini and his colleagues are interested in studying ways to repair the salivary glands after they have been damaged by radiation from cancer treatment. The work on developing this therapy began almost 40 years ago, with much of the past 20 years spent addressing critical steps in the process, like how to introduce new genes into salivary glands, which genes to introduce, and which animal model to test the techniques in.
Through some impressive interdisciplinary collaboration, Dr. Chiorini’s group managed to adapt adeno-associated viruses (AAVs) to function like “trucks” delivering modified genes to cells. AAVs do not provoke a strong response from the human immune system and have other natural characteristics that make them ideal as gene-delivery vehicles. In 2009, former NIDCR investigator Bruce Baum, Ph.D., completed a largely successful proof-of-concept clinical trial that tested the use of the technique to deliver DNA to people whose salivary glands had been damaged by radiation treatment for cancer. About half of the patients in the trial reported improvement.
“The future of gene therapy in the oral cavity is very bright,” Dr. Chiorini concluded.
Salivary glands also have potential to be engineered to take on the functions of other glands, including the pancreas, pituitary gland, thyroid gland, and adrenal glands, possibly allowing gene therapy in the salivary gland to correct deficiencies in these other glands as well.
Next, the audience heard from Dr. Kulkarni, Chief of the Functional Genomics Section and the Director of NIDCR’s Gene Transfer Core. Much of NIDCR’s research on human diseases relies on using mice as animal models. To ensure a ready supply of genetically appropriate animals, NIDCR created the Gene Transfer Core. Dr. Kulkarni has managed the core since it was established in 1995. During his tenure, the facility has made about 2,500 different types of transgenic mice (mice with new genes inserted) and over 100 mouse knockout models (where a gene is deleted or silenced). Notable mouse models made by his team include those for studying genetic conditions that affect the formation of tooth enamel and dentin, namely amelogenesis and dentinogenesis imperfecta. NIDCR’s Gene Transfer Core has also made models for research in mission-critical research areas like sensory biology, immunology, salivary gland biology, and skeletal biology. Many of these models are used by extramural researchers and within NIDCR’s intramural program, including Drs. Young’s and Robey’s groups.
Harnessing CRISPR technology dramatically accelerated Dr. Kulkarni’s work. In the past, it took at least three years to make a knockout model using mouse embryonic stem cells, he said. “Now we can make a knockout model in three months using CRISPR.” In the future, Dr. Kulkarni hopes to further expand his facility’s collaboration with the extramural research community, sharing mouse models and ensuring the models are preserved in repositories.
Then, Dr. Moutsopoulos, Associate Scientific Director for Tenure Track/Assistant Clinical Investigator Faculty Development and Investigator in the Oral Immunity and Infection Section, offered an overview of investigations into periodontal disease. She described the ways NIDCR’s research has been relevant not only in the context of oral health but also within the broader fields of microbiology and immunology. She and her colleagues aim to leverage their focus on rare diseases into a better understanding of the basic biology of human oral diseases, including common forms of periodontitis.
Dr. Moutsopoulos hailed NIH’s interdisciplinary approach to research and the collection of talented scientists working on campus. She specifically cited the ability of intramural researchers to observe a patient in the Clinical Center, go to the lab to study the biological mechanisms underlying that patient’s condition, then return to the patient to attempt novel interventions.
Dr. Lee, Clinical Director and Chief of the Craniofacial Anomalies and Regeneration Section, echoed these sentiments, highlighting how NIDCR’s researchers in the Clinical Center form part of a strong network, building successful collaborations with industry and academic partners and expanding their efforts in clinical trials, which now make up half of their research portfolio.
Looking ahead, Dr. Lee emphasized the importance of continued focus on translating discoveries so that they can be used to benefit the public. She highlighted NIDCR’s clinical study on a treatment for fibrous dysplasia, a rare disease where bone is replaced with fibrous scar tissue, and the identification of SARS-CoV-2 in the oral cavity, both of which were initiated and completed during the pandemic. She praised the efforts of NIDCR’s seven clinical investigators and the team of nurses, physicians, and support staff.
Attendees stuck around for recognition of the contributors to the report Oral Health in America: Advances and Challenges. The venue’s seats had filled up quickly, so any latecomers stood in the back. Most attendees, even those who were standing, stayed until the end. Befitting an anniversary symposium, the mood was celebratory, as the speakers recognized the contributions of NIDCR’s researchers, the strength of the institute’s collaborative network to build on the foundation laid by its predecessors, and the commitment to producing science that benefits researchers and the public for generations to come.
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