L. Latéy Bradford

Participant: PROMISE AGEP Research Symposium

L. Latéy Bradford
Department: Institute for Genome Sciences, Microbiology and Immunology Department
Institution: University of Maryland School of Medicine

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ABSTRACT

Dynamics in the Vaginal Ecosystem and Development of Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) is one of the most common types of infectious vaginitis. VVC is responsible for great morbidity among women of reproductive-age and significant burden to the health care system due to rising vaginitis-related health care costs. My research addresses a critical gap in knowledge related to the importance of the vaginal ecosystem in the development of VVC and the functional interactions that take place within the vagina between the host, the microbiota and the mycobiota[24, 25]. The central hypothesis of this work is that the vaginal microbiota and mycobiota serve as an active ecological barrier to the invasion of Candida spp., however changes in these populations and/or genetic variants of Candida in the community enables the evasion of microbial defense mechanisms and development of VVC. We are leveraging a unique set of vaginal samples and metadata collected in a 10-week daily-sampling prospective longitudinal study to explore changes in microbial community structure and function in women who experienced VVC. Factors associated with the disruption of the vaginal ecosystem or reestablishment of a healthy equilibrium are being identified. In the short-term, this work will provide an in-depth molecular understanding of the underlying causes of the development of VVC. In the long-term, the proposed research is destined to break new ground in the field of women’s reproductive health and improve the quality of life for women who suffer from VVC by enabling improved diagnostic methods and identifying novel targets for new drug development.

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BIOGRAPHICAL SKETCH

I am currently a 6^th-year MD/PhD candidate in the Molecular Microbiology & Immunology graduate program at the University of Maryland School of Medicine. I earned a B.S. in Biology from the University of Maryland, Baltimore County (UMBC) in 2009 and it was there that I first developed a persistent curiosity for research targeted at improving outcomes in women’s and child health. My interests continue to become more refined and focused, but ultimately I am committed to a career that translates biomedical research into effective public health initiatives and interventions. I am passionate about disease prevention and health education, as well as working to reduce health disparities in underserved communities.

GENERAL SUMMARY OF GRADUATE RESEARCH

My research project addresses a critical gap in knowledge related to the importance of the vaginal ecosystem in the development of Vulvovaginal Candidiasis (VVC) and the functional interactions that take place within the vagina between the host, the microbiota and the mycobiota[24, 25]. The primary goals of this project are to better understand the role/functions of the vaginal microbiota and mycobiota in VVC by identifying differences in community composition and gene expression before, during and after an active infection and to evaluate molecular factors that lead to the development of VVC. We are leveraging a unique set of vaginal samples and metadata collected in a 10-week daily-sampling prospective longitudinal study to explore changes in microbial community structure and function in women who experienced VVC. A comprehensive taxonomic survey of the microbiota and mycobiota in vaginal samples will be completed using high-throughput sequencing of 16S rRNA and 18S rRNA genes, respectively. Changes in bacterial and fungal abundance will be measured using validated pan-bacterial and pan-fungal qPCR assays. Metatranscriptomics analysis will be performed on samples selected before, during and after VVC episodes from each woman to identify genes and pathways that are up-regulated during VVC. Finally, whole genome sequencing and comparative analyses of vaginal Candida isolates will be conducted to investigate critical genetic features that enable the colonization and/or invasion of the vaginal mucosa. Taken together, this work will allow us to identify factors associated with the disruption of the vaginal ecosystem or reestablishment of a healthy equilibrium.

SELECTED LIST OF PRESENTATIONS AND PUBLICATIONS

LL Bradford, J Ravel, VM Bruno. Understanding Vulvovaginal Candidiasis Through a Community Genomics Approach. Curr Fungal Infect Rep. June 2013, Volume 7, Issue 2, pp 126-131.
Brotman RM, Bradford LL, Conrad M, Gajer P, Ault K, Peralta L, Forney LJ, Carlton JM, Abdo Z, Ravel J. Association between Trichomonas vaginalis and vaginal bacterial community composition among reproductive-age women. Sex Transm Dis. 2012 Oct;39(10):807-12.
Tole S, Durkan AM, Huang YW, Liu GY, Leung A, Jones LL, Taylor JA, Robinson LA. Thromboxane prostanoid receptor stimulation induces shedding of the transmembrane chemokine CX3CL1 yet enhances CX3CL1-dependent leukocyte adhesion. Am J Physiol Cell Physiol. 2010 Jun;298(6):C1469-80.

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