Reproductive Immunology and Mucosal Immunology
Our group is based in the Departments of Obstetrics and Gynecology, Immunology and Microbiology and Oncology of Wayne State University, the Perinatology Research Branch (PRB) of Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) and the Barbara Ann Karmanos Cancer Institute. We are also a member of the Mucosal Immunology Studies Team (MIST) of the National Institute of Allergy and Infectious Diseases, NIH.
We have four major lines of investigation. Immunological concepts and technologies are integral to our research. We work collaboratively with colleagues in Wayne State University and other leading institutions in the US, Europe and Asia.
First, we study the immune regulation of pregnancy, fetal and child development. A large number of common reproductive and developmental disorders have immunological basis. Our goal is to harness the knowledge gained from our work to develop diagnostic, therapeutic and preventive strategies to reduce adverse pregnancy outcomes, infant mortality and disability.
Humoral Immunity in normal and pathological pregnancies
The function of maternal humoral immunity has been assumed to be unimportant in pregnancy, and B cells were thought to be out-numbered by other immune cells in the uterus and decidua. However, in reproductive mucosal areas, antibodies confer frontline protection by limiting microbial invasion, eliciting immunity against noxious pathogens and promoting ignorance or tolerance to innocuous commensal microbes. Dysregulation of antibody responses are associated with a variety of pregnancy complications. With our expertise in immunology, we are studying the regulation of humoral immune responses in pregnancy. We are also analyzing how mechanisms regulating the normal behaviors of B cells break down in pathological pregnancy, and whether the restoration of these mechanisms can alleviate or prevent diseases.
Mucosal immunity in the female reproductive tract
The female reproductive mucosal immune system protects the host against infections and adapts to a spectrum of physiological events, such as menstruation and pregnancy. During pregnancy, the placental immune system maintains a delicate immunological balance during pregnancy to ensure tolerance to a semi-allogeneic conceptus and surveillance against urogenital pathogens. A shift from this balance underlies many pregnancy complications, such as preeclampsia, intrauterine growth restriction and preterm labor. How the placental immune environment is initiated or maintained is not fully understood. We are identifying novel molecules and cells that play critical roles in the establishment and maintenance of the placental immune environment.
Development of new maternal vaccines
Maternal vaccination, a form of vaccination given to women of child-bearing age before, during or after pregnancy that is aimed at providing the mother, the fetus and the baby against infections that would threaten healthy reproduction, has achieved much progress in the past decades, with several maternal vaccines, such as the inactivated influenza vaccine and tetanus, diphtheria and acellular pertussis (TDaP) vaccine, recommended to all pregnant women in each pregnancy. However, there are still a large number of infectious pathogens aginst which no vaccines are available for pregnant women. Leveraging our expertise in basic immunology, we are studying the humoral immune protection mechansims induced by maternal vaccination to various pathogens using mouse models and human specimens in order to develop maternal vaccines with better efficacy and safety.
Second, we study the regulation of antibody diversification and production in order to understand and treat their defects in immunodeficiency, inflammation and autoimmunity.
Antibody diversification and production by B cells
We apply a diverse array of cellular, histological and molecular techniques to elucidate mechanisms of antibody diversification and production by B cells, including heavy chain class switching from IgM to IgD, IgG, IgA or IgE and somatic hypermutation. These processes are critical for the diversification of the antibody repertoire and the generation of effective immunity against infection and cancer. They critically depend on the enzyme activation-induced cytidine deaminase (AID). Loss-of-function mutations in AID result in immunodeficiency while uncontrolled function of AID predisposes the individual to cancer. The cellular and molecular mechanisms of class switching and somatic hypermutation mediated by AID are under investigation.
Third, we study the pathogenic mechanisms of gynecologic malignancies with the goal of identifying biomarkers for early cancer diagnosis and accurate prognosis and molecular targets for treatment.
Pathogenesis and biomarkers of epithelial ovarian cancer
We employ cell culture-, patient specimen- and mouse model-based strategies to elucidate the cellular and molecular pathways underlying the growth, metastasis and immunomodulation of epithelial ovarian cancer. Our current focuses are the identification of novel biomarkers of ovarian cancer prognosis and the regulation of the ovarian cancer immune microenvironment.
Our work is supported by
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