Autoimmune Diseases; Bacterial Infections; Pregnancy Complications; Pregnancy Complications, Infectious; Antiphospholipid Syndrome; Toll-Like Receptors; Nod Signaling Adaptor Proteins; Immune System Processes
Dr. Abrahams' lab studies Reproductive Immunology with a focus on the impact the immune system and immunological processes have on pregnancy outcome. Her research is concentrated on three areas:
(1) Innate immune responses to infection at the maternal-fetal interface: A primary focus of the lab is to investigate the function of innate immune pattern recognition receptors at the maternal-fetal interface in order to understand how gestational tissues respond to infection, and how these responses play a role in adverse pregnancy outcomes, such as preterm birth. A major focus has been on placental trophoblast responses to infection. Our studies have found that the trophoblast and other gestational cells/tissues express Toll-like receptors (TLRs) and Nod-like receptors (NLRs) which elicit a wide range of effects; ranging from specific antiviral/microbial responses and inflammation to apoptosis.
(2) Mechanisms of antiphospholipid antibody-induced pregnancy complications. Another major area of interest to the lab is the impact antiphospholipid antibodies (aPL) have on a woman's chance of reproductive success. Women with antiphospholipid syndrome are at risk for recurrent pregnancy loss and preeclampsia. aPL are known to directly target the placenta. Studies in the lab are characterizing the mechanisms by which aPL alter trophoblast function. We are also testing the efficacy of various therapeutic agents on trophoblast reposnes to aPL in order to determine better ways to prevent obstetrical problems in these patients.
(3) The role of placental microparticles in the pathogenesis of preeclampsia. Normal pregnancy is associated with the presence of circulating placental microvesicles (MV) and increased shedding and altered immune activation are seen in patients with preeclampsia, suggesting that placental MV may play a role in the pathophysiology of this disease. Studies by the lab have found that placental-derived MV express high levels of the human endogenous retrovirus (HERV), syncytin-1, and have demonstrated a functional role for this protein through its interactions with immune cells.
- Mulla, MJ, Salmon, JE, Chamley, LW, Brosens, JJ, Boeras, CM, Kavathas, KB, Abrahams, VM. A role for uric acid and the Nalp3 inflammasome in antiphospholipid antibody-induced IL-1ß production by human first trimester trophoblast. Plos One 2013 Jun 6;8(6):e
- Kavathas, PB, Boeras, CM, Mulla, MJ, Abrahams, VM. Nod1, but not the ASC inflammasome, contributes to induction of IL-1b secretion in human trophoblasts after sensing of Chlamydia trachomatis. Mucosal Immunology. 2012 Jul 4. [Epub ahead of print]
- Odiari, EA, Mullam MJ, Sfakianaki, AK, Paidas, MJ, Stanwood, NL, Gariepy, A, Brosens, JJ, Chamley, LW, Abrahams, VM. Pravastatin does not prevent antiphospholipid antibody-mediated changes in human first trimester trophoblast function. Human Reproduction. 2012;27:2933-40
- Holder, BS, Tower, CL, Forbes, K, Mulla, MJ, Aplin, JD, Abrahams, VM. Immune cell activation by trophoblast-derived microvesicles is mediated by syncytin 1. Immunology. 2012; 136:184-91
- Cardenas, I., Mulla, M.J., Myrtolli, K., Sfakianaki, A.K., Norwitz, E.R., Tadesse. S., Guller, S., Abrahams, V.M.. Nod1 activation by bacterial iE-DAP induces maternal-fetal inflammation and preterm labor. Journal of Immunology 2011: 187(2):980-6.
- Mulla, M.J., Myrtolli, K., Potter, J. Boeras, C. Kavathas, P.B., Sfakianaki, A.K., Tadesse, S. Norwitz, E.R., Guller, S., Abrahams, V.M. Uric acid induces trophoblast IL-1ß production via the inflammasome: implications for the pathogenesis of preeclampsia