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.
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.
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|Castillo-Azofeifa, David; Seidel, Kerstin; Gross, Lauren et al. (2018) SOX2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis. Development 145:|
|Nguyen, Minh Binh; Cohen, Idan; Kumar, Vinod et al. (2018) FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells. Nat Commun 9:2333|
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|Calamari, Zachary T; Hu, Jimmy Kuang-Hsien; Klein, Ophir D (2018) Tissue Mechanical Forces and Evolutionary Developmental Changes Act Through Space and Time to Shape Tooth Morphology and Function. Bioessays 40:e1800140|
|Hu, Jimmy Kuang-Hsien; Du, Wei; Shelton, Samuel J et al. (2017) An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice. Cell Stem Cell 21:91-106.e6|
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|Wald, Tomas; Spoutil, Frantisek; Osickova, Adriana et al. (2017) Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif. Proc Natl Acad Sci U S A 114:E1641-E1650|
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