Host-Microbial Interactions in the Female Reproductive Tract
Female reproductive tract infections are a critically important problem to global health. Millions of women are affected by sexually transmitted infections, infections during pregnancy, and postpartum infections. Worldwide, infections are the leading cause of infertility, they are a leading cause of premature birth, and infections are a major cause of maternal death during or following childbirth. Gaps in our knowledge of the pathogenesis of these infections have hindered efforts to reduce their burden on women’s health. Innovative strategies are needed to develop better preventive and therapeutic strategies against infections of the female reproductive tract.
The Aronoff lab is addressing the problem of female reproductive tract infections through integrated explorations of host-microbial interactions, microbial pathogenesis, innate immunity, and mucosal immunology. We are primarily interested in understanding how innate immune defenses against bacterial infections are regulated. In particular, our studies focus on toxigenic, Gram positive bacteria that cause life-threatening infections of reproductive-age women. One of these pathogens is the anaerobic bacterium Clostridium sordellii, which causes reproductive tract infections and a unique toxic shock syndrome following childbirth or spontaneous/therapeutic abortions. The other pathogen we study is Group A Streptococcus (GAS), a more common cause of toxic shock syndrome, which is a major cause of postpartum sepsis.
Our lab studies interactions between these toxigenic bacteria and reproductive tract macrophages and epithelial cells. We are particularly interested in the modulation of the behaviors of these cells by a major class of lipid mediators called prostaglandins. Prostaglandins are small molecules, derived from the metabolism of the cell membrane constituent fatty acid called arachidonic acid. Our lab and others have established that prostaglandins (which are produced in abundance at sites of infection) have potent immunoregulatory properties that influence multiple functions of the innate immune system. Investigating how prostaglandins regulate cellular behavior at a molecular level is an important approach to identifying novel pharmacological targets for enhancing host defenses against infection. Through these studies we are gaining a better understanding of the intracellular signaling cascades that regulate antimicrobial behaviors of macrophages and epithelial cells.
In addition to our work on reproductive tract infections, we have active research projects in respiratory diseases (Streptococcus pneumoniae infections) and gastrointestinal diseases (Clostridium difficile colitis). The Aronoff lab provides a highly collaborative, productive and friendly environment for examining microbial pathogenesis, innate immunity, and women's reproductive health.
Dr. Aronoff is also a faculty member of the Graduate Program in Immunology, the Program in Biomedical Sciences, and the Reproductive Sciences Program at the University of Michigan.
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