Event
Ph.D. Dissertation Defense: Darby Steinman
Monday, October 19, 2026
9:00 a.m.
Chemistry Building, Room 1112, The Great Hall
Debbie Chu
301 405 8268
dgchu@umd.edu
Title: Bacterial Extracellular Vesicles in Vaginal Microbe -Host Communication: Understanding Mechanisms That Establish Their Potential As Drug Delivery Vehicles
Committee members:
Dr. Hannah Zierden, Chair
Dr. Gregg Duncan
Dr. Steven M. Jay
Dr. Sara Molinari
Dr. Daniel Nelson, Dean’s Representative
Abstract:
Bacteria within the human body communicate with host tissues through the production of bacterial extracellular vesicles (bEVs). However, this microbe-host signaling between vaginal microbe-derived bEVs and reproductive tissues is not well understood. The distribution, cellular internalization, and biological functions of vaginal microbe-derived bEVs in the female reproductive tract remain unknown, in part due to the complexity and dynamic nature of the vaginal environment. These gaps pose a major obstacle to developing therapeutics to target diseases and bEV-mediated signaling in the female reproductive tract.
Here, we discuss hormone-driven changes to vaginal mucosal barrier properties that affect bEV mobility and subsequent microbe-host signaling. Next, we investigate the role of bEVs in microbe-host communication through characterizing the mobility of both bEVs and whole bacteria through cervicovaginal mucus (CVM). While whole bacteria remain trapped in CVM, bEVs diffuse more rapidly, allowing bEVs to reach upper reproductive tract tissues. We further define the cellular pathways responsible for bEV internalization by vaginal epithelial cells, demonstrating a strong dependence on dynamin-mediated uptake regardless of parent species. We then characterize species-dependent bEV uptake kinetics and subsequent cytokine responses, demonstrating a broad inflammatory response following exposure to dysbiotic G. vaginalis-derived bEVs. In vivo models were used to characterize immune response after chronic exposure to vaginal bEVs, demonstrating that dysbiotic G. vaginalis-derived bEVs induce a general shift in immune response towards antigen presenting cells within the vaginal environment.
Finally, we establish a proof-of-concept bEV platform capable of customization through genetic modification of the parent bacteria. Incorporation of model proteins into bEVs was optimized by modulating culture conditions, resulting in protein loading in ~40% of bEVs. These E. coli bEVs are compatible with both Lactobacillus spp. and reproductive tract cells and are retained within the vaginal tract in vivo for at least 6 hours. We demonstrate a clinically relevant application by displaying targeting peptides on the bEV surface, resulting in increased internalization by cervical cancer cells in vitro. Together, this work advances our understanding of bEV-mediated communication between the vaginal microbiome and reproductive tissues, while establishing a framework for the development of bEVs as drug delivery vehicles.
