GENITAL TRACT BIOLOGY Raina N. Fichorova, MD, PhD, Director DIVISION MEMBERS Radiana T. Trifonova, MD, PhD Rosaria Rita Siervo Sassi, MD Vanessa Tang, MD Jennifer M. Chen, BA Grace Hsu, BS Volunteers: Esther Fleischman, Hidemi Yamamoto, Maksim Sigal MISSION To advance medical knowledge, prevention and cure of inflammatory conditions sequelae in the female genital tract: The main goal of our research program is to advance women’s health. Our research objective is to identify epithelial cell pathways and mucosal immune mechanisms associated with resistance and susceptibility to infection in the female genital tract. ACCOMPLISHMENTS IN AY 2007-2008 The laboratory worked on seven externally funded research projects focused on the diagnosis of inflammatory and infectious conditions of the female genital tract, mechanisms of related morbidity and prevention technologies. In 2007 Dr. Fichorova received an award from the Expanding the Boundaries OB/GYN Research Foundation-BWH and she was promoted to Associate Professor at Harvard Medical School. Major research accomplishments are summarized below. Dr. Fichorova was awarded an NIH grant to study mechanisms of host innate immunity to T. vaginalis. Human trichomoniasis is one of the most common non-viral sexually transmitted infections; over 180 million people worldwide, including 8-10 million Americans, become infected annually. In addition to being a leading cause of vaginitis, trichomoniasis has been linked to preterm delivery (40%), low birth weight, particularly in the African-American community, infertility and cervical cancer. T. vaginalis infection also predisposes women to HIV and other viral infections. Dr. Fichorova’s lab has made major contributions to understanding the immunopathogenic role of lipophosphoglycan (LPG), the major trichomonad surface glycoconjugate, which is in many ways reminiscent of the pathogenic bacterial Gram-negative cell wall component LPS. In collaboration with scientists at SUNY Upstate Medical University New York and the Mass Spectrometry Core at BU School of Medicine, the lab has shown that LPG is essential for the parasite signaling to vaginal epithelial cells and has defined the LPG structural domain that plays a key role in regulating vaginal inflammatory responses (Glyconjugate Journal 2008, Microbicides 2008). We obtained a new NIH R21/R33 award to collaborate with Osel Inc. toward the development of a novel probiotic product to be applied by women as a preventative against the heterosexual transmission of HIV. In 2007 a new award was received from the Contraceptive Research and Development Program (CONRAD) to assess markers of inflammation after vaginal product use; another new research project, funded by Michigan State University, was initiated to identify early biomarkers of preterm labor by characterizing the immunoinflammatory reaction in vaginal swab specimens. The Lab was awarded accreditation by the College of American Pathologists, remaining the flagship for standardization of cytokine testing in human vaginal secretions. Dr. Fichorova led the Cytokine Project of the NIH Microbicide Quality Assurance Program and a multi-center study identifying biological and technical variables affecting cytokine detection (Analytical Chemistry 2008). Another collaborative paper on vaginal cytokines, bacterial vaginosis and HIV was published in 2007 in Infectious Diseases in Obstetrics and Gynecology. EDUCATIONAL MISSION The Lab hosted the 2007 Explorations Program sponsored by the HMS Office for Diversity and Community Partnership (Minority Faculty Development Program, K-12 Programs) and the Biomedical Science Careers Program for middle school students. Dr. Fichorova lectured at an NIH workshop, International Congress of Vaginitis, International Conference and International Meeting Microbicides 2008. Dr. Fichorova has been training a research fellow, Dr. R. Trifonova, who is conducting research on vaginal microbicides. Dr. Trifonova first-authored an oral presentation and received a full scholarship awarded by the Biannual International Conference Microbicides 2008. This year the Lab welcomed a new research assistant, Dr. Vanessa Tang, who is being trained and will perform research while preparing for application to OB/GYN residency programs in 2009. Dr. Tang replaced Dr. Sassi, an OB/GYN from Brazil, who spent ~1.5 years in the laboratory, co-authored two papers and after passing the board exams is beginning clinical residency. Estee Fleischman, a summer intern and undergraduate at Brandeis received the Rapaporte Foundation Summer Internship Grant, awarded by the Women's and Gender Studies Program at Brandeis, for participating in our program. Hidemi Yamamoto, a volunteer, undergraduate student and pre-medicine major at Harvard University Extension School received a Faculty Aide Grant to do research and develop scholarship skill. PARTNERS TEAM PROJECTS Dr. Fichorova’s laboratory continues collaborations with scientists from the BWH Department of Pathology and OB/GYN Epidemiology Center investigating biological mechanisms underlying the link between talc use in genital hygiene, mucosal immune dysregulation and risk of ovarian cancer. Another ongoing collaboration is with Dr. A. Onderdonk at the Channing Laboratory to study vaginal microflora-epithelial interactions under two funded projects. Two new collaborations were established with Channing Lab scientists Dr. M. Gadjeva and Dr. R. Cohen related to infection and immunity and biomarkers of inflammation. GOALS FOR AY 2008-2009 Expand research on vaginal mucosal immunity and continue translational research toward validation of biochemical markers of vaginal inflammation and immune dysfunction. Continue offering educational experience to premedical and Harvard medical students and OB/GYN residents and fellows.