[cid:image004.jpg@01D7B07E.E6E20920] Weldon School of Biomedical Engineering Seminar Series Wednesday, October 13, 2021 9:30-10:20am MJIS 1001 https://purdue-edu.zoom.us/j/95028921977 Understanding the role of the vaginal microbiome in women's reproductive health [cid:image001.jpg@01D7BB5F.BBAD8F40] Alicia Berard, Ph.D. Head, Microbiome & Mucosal Biology Lab Department of Obstetrics, Gynecology & Reproductive Health Max Rady College of Medicine University of Manitoba Abstract: Epithelial dysfunction and immune activation are associated with bacterial vaginosis, but the molecular pathways governing these processes are unclear. To address this, we utilized an integrated 'omics approach to characterize molecular differences in the vaginal mucosa of women with vaginal microbial dysbiosis and evaluated functional mechanisms with bacterial co-cultures and mouse models. Five major microbiome groups were identified in women, with two non-Lactobacillus dominant profiles associating with clinical BV diagnosis. Molecular profiling of vaginal mucosal and tissue samples showed that the master regulator pathway mTOR was a major cell signaling pathway mediating differences in host-bacterial interactions between microbiome groups. Bacterial co-cultures and mouse models indicate that BV-associated bacteria directly cause barrier integrity changes in vitro and may cause physiological dysfunction of vaginal epithelial barrier pathways in vivo, mediated through the mTOR signaling pathway. Further studies on the vaginal mucosal environment and host mTOR are needed to determine how vaginal dysbiosis develops, what drives BV recurrence, and may provide novel BV treatment options. To this end, we have developed a prospective clinical observational study (THRIVE), recruiting women with and without BV. We are collecting vaginal, rectal and blood samples over the course of 6 months to understand whether mTOR expression drives risk of recurrence, and if this pathway can be targeted for modulation using metabolites or mTOR modulators in model systems. Preliminary clinical results from THRIVE participants show that the vaginal microbiome, host proteomic changes and mucosal metabolites change drastically after treatment. Molecular signaling and immune cell differences between controls and BV positive individuals are also observed at baseline, and daily vaginal swabs are providing resolution to show microbiome stability over time. We are continuing to recruit more women into this study to increase our power to understand the drivers of microbiome switchover events and BV recurrence. Bio: Dr. Berard received her Bachelor of Science Honours degree in Biochemistry at the University of Winnipeg in 2006. She started her Master's in Medical Microbiology through the University of Manitoba and transitioned to the PhD program, graduating in 2015. Her PhD work included studies on quantitative proteomics of in vitro cell models infected with reovirus and herpes simplex virus type strains. She completed her Post-doctoral Fellowship through the University of Manitoba, working at the JC Wilt Infectious Diseases Research Center in Dr. Adam Burgener's lab. Her main projects included looking at mucosal systems in HIV pathogenesis and transmission using proteomic and systems biology of samples collected from large clinical cohort and animal model studies, as well as developing imaging and in vitro models to study the mechanistic interactions of the mucosal system barrier and the microbiome. Dr. Berard is currently the head of a Microbiome & Mucosal Biology laboratory located at the Children's Hospital Research Institute of Manitoba, through the University of Manitoba's Obstetrics and Gynecology department. She is also an Adjunct Instructor at Case Western Reserve University. As a co-investigator on international collaboration team grants recently funded, she is leading prospective clinical studies with aims to understand the drivers of recurrent bacterial vaginosis and the role of the vaginal microbiome on progression of cervical cancer in women with high-risk HPV infections. For today's talk she will be focusing on her work understanding the molecular signaling and physiological mechanisms of barrier disruption and inflammation in the context of bacterial vaginosis or "BV"-associated bacteria, and introduce the THRIVE study ("The study of Host-bacterial Relationships and Immune function in different Vaginal Environments"). ~BME Faculty Host: Dr. Douglas Brubaker~ Sincerely, Cindy Holderbaum Senior Administrative Assistant & Schedule Deputy Weldon School of Biomedical Engineering Martin C. Jischke Hall of Biomedical Engineering, (MJIS) Rm. 1021 206 S. 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