The long-term goals of the applicant are to become a successfully funded, independent, craniofacial
developmental biologist, conducting human-disease-focused and translatable research aimed at improving
dental, oral, and craniofacial health. This overarching goal will be actualized by the implementation of a highly
coordinated, thorough, and integrated career development plan including components of mentored guidance
and training, an adept research environment, and a complementary research project. First, a career
development plan comprised of a mentor, advisory committee, collaborators, and courses and conferences
has been established to provide the applicant with the skills and guidance to transition into a position of
independence in a timely manner. The mentor, Dr. Williams, is a successfully funded researcher and leading
expert in craniofacial biology and is thus well suited to oversee the applicant’s training. The advisory committee
includes both internal and external members that will provide critical guidance and feedback on aspects of
career development and technical components of cranial bone, tooth, enamel, cell culture, bioinformatic, and
gene-editing biology. The committee also includes two young faculty members who will specifically assist the
applicant in components directly related to career transition. In addition, courses in bioinformatics and
conferences on bone and tooth development and biomineralization are included to facilitate these components
of the training program. Second, an adept research environment – the Department of Craniofacial Biology, the
University of Colorado, along with associated resources, core facilities, and faculty members not directly
involved in the applicant’s advisory committee – is established to provide assurance of the applicant’s success.
Third, a research project has been proposed to facilitate training of the applicant in new areas of biology
essential for his path to independence while simultaneously maintaining the key goals of improving dental, oral,
and craniofacial health. Central to these goals are understanding the unique gene regulatory networks driving
cranial skeletal mineralization – a process that is well described in the mesoderm-derived trunk skeleton yet
lacks clarity in the cranial skeleton owing to its unique developmental origins. To this end, the research
proposal utilizes three aims to test the important hypothesis that Memo1 and Runx2 genetically integrate to
drive mineralization of key craniodental structures, including teeth and bones. Aim I will establish whether
Memo1 expression is directly regulated by RUNX2 in the context of in vivo cranial endochondral ossification
and in vitro amelogenesis. Aim II will more specifically determine the role of MEMO1 in cranial endochondral
ossification and its genetic integration with Runx2-II in this process. Finally, Aim III will establish the role these
molecules play in mineralization of the enamel layer during tooth development. Collectively, this
comprehensive career development and research plan will ensure the successful transition of the applicant
from a dependent research position into one of well-prepared independence.