By discovering the strategies that animals normally use to renew and regenerate their tissues, we can lay a foundation for regenerative approaches in humans. One of the principal long-term goals of my laboratory is to understand mammalian renewal and regeneration by integrating developmental and evolutionary perspectives. To do this, we are using the dentition as a model and are taking advantage of a remarkable property that is found in diverse mammalian species, which is the ability to grow teeth continuously based on the presence of adult stem cells. Despite initial progress, many gaps and challenges in our knowledge remain. We are still in the early stages of understanding how dental stem cells in the incisor epithelium behave, and we know very little about the mesenchymal stem cells. We also have a great deal to learn about how dental stem cells evolved and how they arise in the embryo during development. The overall scope of the research program proposed here will be to contend with these fundamental questions: How do adult stem cells enable the organ to renew? How do the stem cells in teeth respond to environmental influences such as hibernation and force? How did stem cells emerge during evolution of the mammalian dentition? How do progenitor cells in the embryo provide the starting materials for tooth development? Can we target tooth progenitors to cure disease? The impact of our work will be to provide a solid basic science foundation for future regenerative approaches by obtaining deep insight into a system of natural mammalian dental renewal.

Public Health Relevance

Dental decay and tooth loss constitute an important public health issue, and many patients with birth defects have tooth anomalies that require repair. A thorough understanding of the molecular processes that normally drive tooth formation and renewal will provide an important underpinning for biologically-inspired therapies. We propose to use both evolutionary and developmental approaches to achieve a greater understanding of the regulation of stem cell-driven tooth renewal, and in the long run the results from these studies will be useful for repair and regeneration of teeth and other organs.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Unknown (R35)
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Special Emphasis Panel (ZDE1)
Program Officer
Shum, Lillian
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University of California San Francisco
Schools of Dentistry/Oral Hygn
San Francisco
United States
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Kalha, Solja; Shrestha, Bideep; Sanz Navarro, Maria et al. (2018) Bmi1+ Progenitor Cell Dynamics in Murine Cornea During Homeostasis and Wound Healing. Stem Cells 36:562-573
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