This proposed K23 Award will assist Loris Hwang, MD, at the University of California, San Francisco, in establishing herself as a young investigator in the clinical translational research of the biology of the reproductive tract in adolescent women. The K23 will provide Dr. Hwang the support necessary to accomplish the following goals: 1) to conduct clinical translational research on cervical epithelial maturity, mucosal immunity, and Chlamydia trachomatis infection in adolescents;2) to gain knowledge of basic and mucosal immunology;3) to gain practical experience and knowledge of immunoassay techniques to measure mucosal immune factors;4) to become proficient in advanced technologies for manipulation and analysis of digital images;and 5) to develop an independent clinical translational research career. To achieve these goals, Dr. Hwang has assembled a complementary mentoring team. Her primary mentor, Anna-Barbara Moscicki MD, conducts longitudinal studies of natural HPV infection and has extensive experience in the evaluation of cervical maturity and molecular epidemiology studies of mucosal immunology. Her co-mentor, Richard S. Stephens, PhD MPH, studies the host-microbe interaction in C. trachomatis infection from a cellular microbiology perspective. C. trachomatis is the most common reportable bacterial sexually transmitted infection (STI) in the US, with the highest age-specific rates in adolescent women ages 15-24 years. Cervical infection typically induces a host inflammatory response. However, over-zealous inflammation can lead to serious sequelae including pelvic inflammatory disease and infertility. During adolescence, normal cervical epithelial maturation consists of the transformation of the immature columnar epithelium into more mature squamous epithelium. This area of transformation has been shown to be richer in immune activation markers than mature epithelium, possibly putting adolescents at increased risk for complications. Accessing the resources of an on-going longitudinal study of the natural history of HPV in adolescent women, Dr. Hwang will: 1) examine the association between extent of cervical immaturity and the expression of mucosal immune factors in women without any known cervical or vaginal infections;and 2) examine the associations among the extent of cervical immaturity, incidence of cervical C. trachomatis infection, and expression of mucosal immune factors during C.trachomatis infection. Study designs will include longitudinal intra-woman and interwomen comparisons of immune factors, acquisition of infection, and response to infection. Other factors including contraception use, tobacco use, and sexual behaviors will also be included in the analyses. Public health relevance: The findings of this study will contribute to our understanding of the immunobiology of the adolescent female reproductive tract and may help inform future prevention and therapy of STIs.
