Autoimmune Diseases; Fetal Membranes, Premature Rupture; Immunity, Innate; Placenta; Pregnancy Complications; Pregnancy Complications, Infectious; Pregnancy in Diabetics; Antiphospholipid Syndrome; Antibodies, Antiphospholipid; MicroRNAs; Toll-Like Receptors; Nod Signaling Adaptor Proteins; Exosomes; Immune System Processes; Inflammasomes
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. Our studies have found that the placental trophoblast and the fetal membranes express Toll-like receptors (TLRs), Nod-like receptors (NLRs), and inflammasome components. We also study these immune systems in the context of non-infectious stimuli during pregnancy. Through these innate immune pathways, these tissues/cells 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 characterize the mechanisms by which aPL alter trophoblast function. We use mechanistic findings to identify new predictors of adverse pregnancy outcomes in these pateints, We also use our in vitro studies to test the efficacy of various therapeutic agents on trophoblast resposnes 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 exosomes and increased shedding and altered immune activation are seen in patients with preeclampsia, suggesting that placental MV and exosomes 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.We have also identified microRNAs enriched in trophoblast-derived exosomes and are examining their biological function.
- Viral single stranded RNA induces a trophoblast pro-inflammatory and antiviral response in a TLR8-dependent and -independent manner. Potter JA, Garg M, Girard S, Abrahams VM. Viral single stranded RNA induces a trophoblast pro-inflammatory and antiviral response in a TLR8-dependent and -independent manner. Biol Reprod. 2015 Jan;92(1):17
- Glucose and metformin modulate human first trimester trophoblast function: a model and potential therapy for diabetes-associated uteroplacental insufficiency. Han CS, Herrin MA, Pitruzzello MC, Mulla MJ, Werner EF, Pettker CM, Flannery CA, Abrahams VM. Glucose and metformin modulate human first trimester trophoblast function: a model and potential therapy for diabetes-associated uteroplacental insufficiency. Am J Reprod Immunol. 2015 Apr;73(4):362-71
- Aspirin-triggered lipoxin prevents antiphospholipid antibody effects on human trophoblast migration and endothelial cell interactions. Alvarez AM, Mulla MJ, Chamley LW, Cadavid AP, Abrahams VM. Aspirin-triggered lipoxin prevents antiphospholipid antibody effects on human trophoblast migration and endothelial cell interactions. Arthritis Rheumatol. 2015 Feb;67(2):488-97
- Human fetal membranes generate distinct cytokine profiles in response to bacterial Toll-like receptor and Nod-like receptor agonists. Hoang M, Potter JA, Gysler SM, Han CS, Guller S, Norwitz ER, Abrahams VM. Human fetal membranes generate distinct cytokine profiles in response to bacterial Toll-like receptor and Nod-like receptor agonists. Biol Reprod. 2014 Feb 27;90(2):39
- A role for uric acid and the Nalp3 inflammasome in antiphospholipid antibody-induced IL-1β production by human first trimester trophoblast. Mulla MJ, Salmon JE, Chamley LW, Brosens JJ, Boeras CM, Kavathas PB, Abrahams VM. A role for uric acid and the Nalp3 inflammasome in antiphospholipid antibody-induced IL-1β production by human first trimester trophoblast. PLoS One. 2013 Jun 6;8(6):e65237
- Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8 secretion through activation of Toll-like receptor 8. Gysler SM, Mulla MJ, Guerra M, Brosens JJ, Salmon JE, Chamley LW, Abrahams VM. Mol Hum Reprod. 2016 Jul;22(7):465-74.27029214