Dental caries, the most common, chronic, infectious childhood disease, has a substantial impact on children?s quality of life. The high prevalence of dental caries that persists despite its preventability necessitates improvement in diagnostics and therapeutic interventions for this young and vulnerable population. Over the years, significant progress has been made in caries research. Despite these advances, research gaps remain, limiting the ability to answer two fundamental questions: 1) Why do not all individuals with elevated levels of Streptococcus mutans (Sm), an important infectious, cariogenic bacterium, develop caries? 2) How does host genetic variation contribute to the susceptibility to dental caries? The former continues to be a major enigma in the field of oral microbiology. Though host susceptibility has been recognized as an important determinant in medical infectious diseases, it remains an under-studied factor in caries research. Dr. Nini Tran, an Assistant Professor at the UCLA School of Dentistry, is a pediatric dentist-scientist with a well-rounded training and a long-standing commitment to a research career. The career development plan enables Dr. Tran to gain additional expertise in three areas: 1) Microbiology and microbiome research, 2) biostatistics and bioinformatics, 3) saliva diagnostics. Dr. Tran will be supported by an outstanding multidisciplinary mentoring team with expertise to cover all elements of her research and career development. Dr. David Wong, a pioneer in the field of saliva diagnostics, is her primary mentor; Dr. Wenyuan Shi, Dr. Jeff Miller, Dr. Renate Lux, Dr. Xuesong He, Dr. Floyd Dewhirst, and Dr. Ann Griffen are the leading microbiology and microbiome experts; Dr. David Elashoff provides biostatistics support, while Dr. Jeff McLean has expertise in next-generation sequencing and bioinformatics analyses. Through a tailored curriculum of courses, workshops and the proposed research, Dr. Tran will develop crucial skills to achieve her goal of becoming a successful independent clinician-scientist in the field of childhood caries diagnostics and therapeutics. This research investigates a discordant, preschool child population whose caries status contradicts what is expected based on their Sm level in comparison to the accordance counterpart. Integrating innovative study design and novel tools, the research plan aims to 1) characterize Sm strain individuality and its ecological relationship within different microbial communities, 2) explore salivary host biomarkers related to childhood caries, and 3) validate Sm-associated microbial virulence signatures and host salivary biomarkers for precise and comprehensive caries assessment. This research will generate the basis for R01 proposals, focusing on oral microbiome inter- species interaction, and host and oral microbial interaction related to childhood caries susceptibility, and the development of diagnostics and therapeutics for childhood caries. Finally, this award will position Dr. Tran to become a top tier pediatric dentist-scientist, and enable her to make a significant contribution to the field of pediatric dentistry.

Public Health Relevance

! Dental caries, though preventable, is the most common, chronic infectious childhood disease with substantial impact on children?s quality of life. With innovative study design and novel tools, this proposal aims to uncover knowledge gaps in microbiology and host susceptibility of childhood dental caries. Findings from this research will give insight into why certain children are more susceptible or resistant to dental caries and potentially lead to the development of a saliva-based diagnostic tool using the identified microbial and host genetic markers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DE027718-03
Application #
9977157
Study Section
NIDR Special Grants Review Committee (DSR)
Program Officer
King, Lynn M
Project Start
2018-09-15
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095