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Our world is at a turning point with biological and social pathogens wreaking havoc at the same time that science and technology are exploding with new discoveries. It is a pivotal time for the new report Oral Health in America: Advances and Challenges to be released and a pivotal time for our profession to take action and lead. The art, science, and practice of dentistry is very different from 20 y ago when the original Surgeon General’s report was released. We are on the precipice of individualized health care where providers will collaborate to deliver diagnostics and therapeutics that are data driven and inclusive of the social determinants of health. To move forward with alacrity requires a strong scientific foundation, effective educational approaches, an understanding of the upstream determinants of health, and partnerships across the health professions and beyond. Oral health has never been more important, and now is the time for our profession to further develop, elevate, and translate the science into practice and policy to improve the nation’s health.

Orofacial clefts and their management impose a substantial burden on patients, on their families, and on the health system. Under the current standard of care, affected patients are subjected to a lifelong journey of corrective surgeries and multidisciplinary management to replace bone and soft tissues, as well as restore esthetics and physiologic functions while restoring self-esteem and psychological health. Hence, a better understanding of the dynamic interplay of molecular signaling pathways at critical phases of palate development is necessary to pioneer novel prenatal interventions. Such pathways include transforming growth factor–β ( Tgfβ), sonic hedgehog ( Shh), wingless-integrated site ( Wnt)/β-catenin, bone morphogenetic protein ( Bmp), and fibroblast growth factor ( Fgf) and its associated receptors, among others. Here, we summarize commonly used surgical methods used to correct cleft defects postnatally. We also review the advances made in prenatal diagnostics of clefts through imaging and genomics and the various in utero surgical corrections that have been attempted thus far. An overview of how key mediators of signaling that drive palatogenesis are emphasized in the context of the framework and rationale for the development and testing of therapeutics in animal model systems and in humans is provided. The pros and cons of in utero therapies that can potentially restore molecular homeostasis needed for the proper growth and fusion of palatal shelves are presented. The theme advanced throughout this review is the need to develop preclinical molecular therapies that could ultimately be translated into human trials that can correct orofacial clefts at earlier stages of development.

Gender inequality in science, medicine, and dentistry remains a central concern for the biomedical research workforce today. Although progress in areas of inclusivity and gender diversity was reported, growth has been slow. Women still face multiple challenges in reaching higher ranks and leadership positions while maintaining holistic success in these fields. Within dental research and academia, we might observe trends toward a more balanced pipeline. However, women continue to face barriers in seeking leadership roles and achieving economic equity and scholarship recognition. In an effort to evaluate the status of women in dental research and academia, the authors examined the role of the International Association for Dental Research (IADR), a global research organization, which has improved awareness on gender inequality. The goal of this article is to review five crucial issues of gender inequality in oral health research and academics—workforce pipeline, economic inequality, workplace harassment, gender bias in scholarly productivity, and work-life balance—and to discuss proactive steps that the IADR has taken to promote gender equality. Providing networking and training opportunities through effective mentoring and coaching for women researchers, the IADR has developed a robust pipeline of women leaders while promoting gender equality for women in dental academia through a culture shift. As knowledge gaps remained on the levels of conscious and unconscious bias and sexist culture affecting women advancement in academics, as well as the intersectionality of gender with race, gender identity, ability status, sexual orientation, and cultural backgrounds, the IADR has recognized that further research is warranted.

Preservation of a vital dental pulp is a central goal of restorative dentistry. Currently, there is significant interest in the development of tissue engineering scaffolds that can serve as biocompatible and bioactive pulp-capping materials, driving dentin bridge formation without causing cytotoxic effects. Our earlier in vitro studies described the biocompatibility of multidomain peptide (MDP) hydrogel scaffolds with dental pulp–derived cells but were limited in their ability to model contact with intact 3-dimensional pulp tissues. Here, we utilize an established ex vivo mandible organ culture model to model these complex interactions. MDP hydrogel scaffolds were injected either at the interface of the odontoblasts and the dentin or into the pulp core of mandible slices and subsequently cultured for up to 10 d. Histology reveals minimal disruption of tissue architecture adjacent to MDP scaffolds injected into the pulp core or odontoblast space. Additionally, the odontoblast layer is structurally preserved in apposition to the MDP scaffold, despite being separated from the dentin. Alizarin red staining suggests mineralization at the periphery of MDP scaffolds injected into the odontoblast space. Immunohistochemistry reveals deposition of dentin sialophosphoprotein by odontoblasts into the adjacent MDP hydrogel, indicating continued functionality. In contrast, no mineralization or dentin sialophosphoprotein deposition is evident around MDP scaffolds injected into the pulp core. Collagen III expression is seen in apposition to gels at all experimental time points. Matrix metalloproteinase 2 expression is observed associated with centrally injected MDP scaffolds at early time points, indicating proteolytic digestion of scaffolds. Thus, MDP scaffolds delivered centrally and peripherally within whole dental pulp tissue are shown to be biocompatible, preserving local tissue architecture. Additionally, odontoblast function and pulp vitality are sustained when MDP scaffolds are intercalated between dentin and the odontoblast region, a finding that has significant implications when considering these materials as pulp-capping agents.

To date, surgical interventions are the only means by which craniofacial anomalies can be corrected so that function, esthetics, and the sense of well-being are restored in affected individuals. Unfortunately, for patients with cleft palate—one of the most common of congenital birth defects—treatment following surgery is prolonged over a lifetime and often involves multidisciplinary regimens. Hence, there is a need to understand the molecular pathways that control palatogenesis and to translate such information for the development of noninvasive therapies that can either prevent or correct cleft palates in humans. Here, we use the well-characterized model of the Pax9−/−mouse, which displays a consistent phenotype of a secondary cleft palate, to test a novel therapeutic. Specifically, we demonstrate that the controlled intravenous delivery of a novel mouse monoclonal antibody replacement therapy, which acts as an agonist for the ectodysplasin (Eda) pathway, can resolve cleft palate defects in Pax9−/−embryos in utero. Such pharmacological interventions did not reverse the arrest in tooth, thymus, and parathyroid gland development, suggesting that the relationship of Pax9 to the Eda/Edar pathway is both unique and essential for palatogenesis. Expression analyses and unbiased gene expression profiling studies offer a molecular explanation for the resolution of palatal defects, showing that Eda and Edar-related genes are expressed in normal palatal tissues and that the Eda/Edar signaling pathway is downstream of Pax9 in palatogenesis. Taken together, our data uncover a unique relationship between Pax9 and the Eda/Edar signaling pathway that can be further exploited for the development of noninvasive, safe, and effective therapies for the treatment of cleft palate conditions and other single-gene disorders affecting the craniofacial complex.

Scientific opportunities have never been better than today! The completion of the Human Genome project has sparked hope and optimism that cures for debilitating conditions can be achieved and tailored to individuals and communities. The availability of reference genome sequences and genetic variations as well as more precise correlations between genotype and phenotype have facilitated the progress made in finding solutions to clinical problems. While certain craniofacial and oral diseases previously deemed too difficult to tackle have benefited from basic science and technological advances over the past decade, there remains a critical need to translate the fruits of several decades’ worth of basic and clinical research into tangible therapies that can benefit patients. The fifth Annual Fall Focused Symposium, “Translational Genetics – Advancing Fronts for Craniofacial Health”, was created by the American Association for Dental Research (AADR) to foster its mission to advance interdisciplinary research that is directed toward improving oral health. The symposium showcased progress made in identifying molecular targets that are potential therapeutics for common and rare dental diseases and craniofacial disorders. Speakers focused on translational and clinical applications of their research and, where applicable, on strategies for new technologies and therapeutics. The critical needs to transfer new knowledge to the classroom and for further investment in the field were also emphasized. The symposium underscored the importance of basic research, chairside clinical observations, and population-based studies in driving the new translational connections needed for the development of cures for the most common and devastating diseases involving the craniofacial complex.

The 4th Annual AADR Fall Focused Symposium (FFS), “Oral Health Disparities Research and the Future Face of America”, took place on November 3-4, 2011 in Washington, DC. The FFS strategy was developed by the AADR to help provide additional opportunities for members to engage in research discussions during the year by identifying specific research topics of interest among the 21 Scientific Groups and 4 Networks of the IADR and targeting a focused topic area for the FFS. The conference attracted an international group of approximately 120 registrants, including participants from Canada, India, Mexico, and China; 4 oral sessions and 32 poster presentations were offered.

The need for women in academia to unite was seen in 1881, when Professors Marion Talbot and Ellen Richards founded the American Association of University Women. During this “Progressive Era”, women suffragists fought for and gained the right to vote, first in New Zealand (1893) and later in the United States (1920). As this first wave of feminism grew, it was highlighted by French philosopher Simone de Beauvoir in her book Second Sex, on gender inequality in a patriarchic society (Beauvoir, 1949). Betty Friedan’s The Feminine Mystique sparked the second wave of feminism, presenting the needs of women trapped in a life that they did not necessarily choose (Friedan, 1963). These movements culminated with The Equal Pay Act (1963) and The Equal Rights Amendment (1972), denouncing pay and sex discrimination for women, currently ratified in 35 U.S. states (113th Congress Joint Resolution 10, 2013). These advances led to the Women in Science and Technology Equal Opportunity Act, ensuring that “men and women have equal opportunity in education, training, and employment in scientific and technical fields” (Carter, 1980) and resulting in increased numbers of female investigators funded by the National Science Foundation (24%) and the National Institutes of Health (27%) (NSF, 2012; NIH, 2012). While these social and civil achievements improved the status of women in academia, there are several career challenges remaining related to an increasingly complex work environment. Although the Council of Graduate Education report shows that women are earning more doctoral degrees (52.4%) than men (Allum et al., 2012), women are still held back in achieving successful careers in academics (Shen, 2013). The “Beyond Bias and Barriers” report (National Research Council, 2007) clearly demonstrated that women are less likely to achieve tenure in academic institutions and are often expected to meet higher standards than their male counterparts. Generally, tenure policies lack flexibility for women during their junior faculty/childbearing years (Marchant et al., 2007). Departmental climates have also been shown to influence higher attrition rates among women since they tend to be less satisfied with their jobs and thus are more likely to quit (Nesbitt et al., 2003). Consequently, the conflicts between personal and professional life develop and strongly affect women in terms of faculty promotion and retention, with 40% of women more likely to exit the tenure track for adjunct positions (National Research Council, 2007). When examining global gender issues, the World Economic Forum (Hausmann et al., 2008) measured the gender gap according to 4 distinct criteria: economic participation and opportunity, educational attainment, political empowerment, and health and survival. The Nordic countries are on the top of the list, confirming their consistent gender equality priorities, with the United States ranked 27th, showing modest improvements in wage inequality and political empowerment (Hausmann et al., 2008). These results correlate with the European Union data on gender and research funding (European Commission, 2009), where the Nordic countries are considered proactive, with policies that secure women’s participation in research by encouraging grant applications from women, increasing numbers of women on review boards, and promoting funding transparency. Unlike the United States, the European Commission has been mandating 40% women participation on advisory boards for research funding programs (Vernos, 2013), striving to eliminate bias and enhance the funding success of women academicians in all 27 countries. Despite the Equal Pay Act, salary inequality between men and women has been recognized across all fields and academic appointment levels (West and Curtis, 2006), with women medical scientists earning 80% of male median wages (Goldberg Dey and Hill, 2007). This pay gap, established as early as one year post-bachelor’s degree, widens by 10 years post-degree (69%) and it is consistent for the level of education: Master’s degree (76%), professional degree (72%), and doctoral degree (80%) (Goldberg Dey and Hill, 2007). Among dental faculty, men are consistently compensated at a higher level than women (ADEA, 2011, 2013) (Table). In an examination of the mean salaries for women vs. men in senior dental school positions, where men hold positions at a 3:1 ratio over women, the differentials currently range from $2,806 to $93,443 (Table). The comparative Table shows that the salary gap between women and men has not only not improved in the past two years but has also widened (ADEA, 2011, 2013). Table. Guaranteed Annual Salary of Full-time Faculty by Primary Appointment and Gender in 2008-2009 and 2010-2011 Since social models have changed and continue to evolve, it is hoped that women will not have to face dilemmas in balancing careers with child-rearing (Ledford et al., 2013). “As more women lean in their careers, more men lean in their families” (Sandberg, 2013). To increase women’s participation in academic leadership, paid maternity/paternity leave and a delayed ‘tenure clock’, as well as consideration and selection of women as finalists for leadership positions, the presence of women on research committees and scientific review and editorial boards, should not be just mandates but an institutional strategic priority. Clearly, issues facing women in academia are multiple and complex, influenced by many personal/perceptual as well as social or state/federal barriers to equality. Recent evidence showed that several dental schools did not offer paid maternity or paternity leave (3.1%), an automatically delayed ‘tenure clock’ with childbirth or adoption (13.3%), dual career appointments (21.9%), and mandatory representation on search committees (15.6%) (Dannels et al., 2009). Analysis of these data stresses the need for critical institutional policies that will promote the career advancement of women in dental academics. Today, there are numerous leadership programs preparing women academicians for better navigation of the labyrinth of academic life and to meet their fullest potential, such as the American Dental Education Association Leadership Institute and Executive Leadership in Academic Medicine (ELAM). Both programs have been successfully promoting the career advancement of women, with currently 15.3% of U.S. dental school deans being women, of whom 60% were ELAM graduates (ADA, 2013). Moreover, over the past decades, the number of women dental students has increased from 23.80% in the early 1980s to 46.6% in 2010 (Gonzalez et al., 2011), resulting in increased enrollment of women in advanced education programs (40.2%) (ADA, 2012) and increased participation in dental academia (ADEA, 2013). Further, Drs. Martha Somerman and Isabel Garcia currently serve as the Director and Deputy Director, respectively, of the National Institute of Dental and Craniofacial Research (NIDCR), demonstrating the presence of women in dental research and leadership at the national level. In 2011, the International Association for Dental Research (IADR) established the “Women in Science” Network with a mission to focus on women’s issues related to career development and health research. The network’s goals are to examine dental academia policies and benefits related to key issues, such as recruitment and retention, promotion and tenure, salary, and childcare, as well as mentorship of junior women faculty and graduate trainees. The Women in Science Network is supportive of our academic institutions developing, encouraging, empowering, and equally promoting faculty regardless of their gender. The network, currently with 181 active and student members, has an active presence in every American Association for Dental Research (AADR) and International Association for Dental Research (IADR) meeting, organizing symposia and workshops with a focus on increasing women’s participation in dental academia, holding business and brainstorming meetings, as well as mentoring graduate students and junior faculty. Dr. Marie Nylen provided a legacy for change through her leadership as the first female president of both the AADR (1979-1980) and the IADR (1981-1982). Since the mid-1990s, the role of women in leadership positions in IADR/AADR has expanded, with 7 out of 15 female IADR presidents (46.7%) and 6 out of 16 female AADR Presidents (37.5%) – excellent statistics for progressive organizations that continue to foster the development of women scientists, clinicians, and educators for future leadership roles.

Experimental and animal studies, as well as genetic mutations in man, have indicated that the development of dentition is under the control of several genes. So far, mutations in MSX1 and PAX9 have been associated with dominantly inherited forms of human tooth agenesis that mainly involve posterior teeth. We identified a large kindred with several individuals affected with molar oligodontia that was transmitted as an isolated autosomal-dominant trait. Two-point linkage analysis using DNA from the family and polymorphic marker D14S288 in chromosome 14q12 produced a maximum lod score of 2.29 at Θ = 0.1. Direct sequencing of exons 2 to 4 of PAX9revealed a cytosine insertion mutation at nucleotide 793, leading to a premature termination of translation at aa 315. Our results support the conclusion that molar oligodontia is due to allelic heterogeneity in PAX9, and these data further corroborate the role of PAX9 as an important regulator of molar development.

The role of stable transcription complexes in initiating and consolidating programs of gene expression during lineage specification has been extensively studied. Despite the progress made in the identification of key molecules of tooth initiation and patterning, the mechanisms leading to cell differentiation during odontogenesis are unknown. Odontoblasts are exclusive dentin-producing cells that are phenotypically and functionally distinct from osteoblasts. However, not much is known about the precise determinants of odontoblast terminal differentiation-in particular, how the fate of these cells becomes delineated from that of osteogenic mesenchyme. Cbfa1(-/-) mice completely lack osteoblasts and bone, while tooth development arrests at the time of odontoblast differentiation. The purpose of this paper is to overview our studies on the role of Cbfa1 in odontoblast determination and differentiation using the Cbfa1(-/-) mouse model and various experimental approaches. Our expression analyses confirm the down-regulation of Cbfal expression in newly differentiated and functional odontoblasts. Second, we demonstrate that Cbfa1(-/-) incisor organs arrest at a later stage than molars, and that al(I) :ollagen, a marker of odontoblast differentiation shared in common with osteoblasts, is not significantly affected by the absence of the transcription factor. Interestingly, Dspp expression in Cbfa1(-/-) appeared markedly down-regulated in putative odontoblasts. The overexpression of Cbfa1 in an odontoblast cell line (MDPC-23) results in the selective down-regulation of Dspp and not type I collagen. It is likely that, in addition to its influence on tooth epithelial morphogenesis, Cbfa1 plays a non-redundant and stage-specific role in the lineage determination and terminal differentiation of odontoblasts from dental papilla mesenchyme.

A frameshift mutation recently identified within the paired domain of the transcription factor, PAX9, has been linked to a unique form of oligodontia in a single, multigenerational family (Stockton et al., 2000). We now describe the phenotypic and segregation analyses of this remarkable kindred, the initial approach taken to identify a candidate gene involved in this form of oligodontia, and the power of this single-family pedigree to generate significant linkage in a genome search. Of the 43 family members enrolled in this study, 21 individuals were affected with several congenitally missing permanent teeth. The pattern of inheritance of the oligodontia trait suggested the involvement of a single gene bearing a dominant mutation. To various degrees, affected members lacked permanent first, second, and third molars in all four quadrants. Several individuals with missing molars also lacked second premolars-most commonly, maxillary second premolars and mandibular central incisors. To the best of our knowledge, this pattern of non-syndromic, familial tooth agenesis has not been previously described in the literature. Since a missense mutation in the homeobox gene, MSX1, was previously linked to tooth agenesis in a single family lacking second premolars and third molars, we performed a mutational analysis of MSX1 by PCR. The absence of a mutation in exons 1 and 2 of MSX1 suggested that allelic mutations in the coding region of MSX1 are not associated with this phenotypically distinct form of oligodontia. Computer simulation of linkage analysis further proved that this pedigree alone was sufficient to generate a significant result for a total genome scan.

D’Souza RN, Dunnvald M, Frazier-Bowers S, Polverini PJ, Wright JT, de Rouen T, Vieira AR (2013). Translational genetics: Advancing fronts for craniofacial health. J Dent Res 92:1058-1064. (Original DOI: 10.1177/0022034513507954 )