Dr. Abrahams' Lab

Research Interests

Innate immune responses to infection at the maternal-fetal interface

A primary focus of the Abrahams 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 infectious components. Studies in the lab have found that the trophoblast and other gestation cells and tissues expresses Toll-like receptors (TLRs) and Nod-like receptors (NLRs) and these elicit a wide range of effects; ranging from specific antiviral/microbial responses and inflammation to apoptosis. Moreover, these varied responses towards infectious components are regulated by specific downstream signaling pathways.

Mechanisms of antiphospholipid antibody-induced pregnancy complications

Another major area of interest to the Abrahams lab is the impact antiphospholipid antibodies have on a woman's chance of reproductive success. Women with antiphospholipid syndrome are at risk for recurrent pregnancy loss, preterm labor and preeclampsia. While antiphospholipid antibodies are known to directly target the placenta and impact trophoblast function, the precise mechanisms involved are poorly understood. Studies in the lab are characterizing the mechanisms by which antiphospholipid antibodies alter trophoblast function. We are also using our in vitro model to test the efficacy of various therapeutic agents in order to determine better ways to prevent obstetrical problems in these patients.

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 compared the effect of placental-derived MV from normal and preeclamptic patients on peripheral blood immune cell activation. Moreover, we 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.

Lab Members


Bio Profile

Vikki Abrahams, PhD

Principal Investigator

Associate Professor of Obstetrics, Gynecology, and Reproductive Sciences

Bio Profile

Sarah Cross, MD

Instructor in Obstetrics, Gynecology, and Reproductive Sciences

Bio Profile

Stefan Gysler

Medical Student

Bio Profile

Nicole Martin

Undergraduate Student

Publications

Luley L, Schumacher A, Mulla MJ, Franke D, Löttge M, Fill Malfertheiner S, Tchaikovski SN, Costa SD, Hoppe B, Abrahams VM, Zenclussen AC: Low molecular weight heparin modulates maternal immune response in pregnant women and mice with thrombophilia. Am J Reprod Immunol. 2015 May; 2014 Dec 11. PMID: 25496123

Norwitz ER, Bonney EA, Snegovskikh VV, Williams MA, Phillippe M, Park JS, Abrahams VM: Molecular Regulation of Parturition: The Role of the Decidual Clock. Cold Spring Harb Perspect Med. 2015 Apr 27; 2015 Apr 27. PMID: 25918180

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; 2014 Nov 14. PMID: 25394884

Andrade D, Kim M, Blanco LP, Karumanchi SA, Koo GC, Redecha P, Kirou K, Alvarez AM, Mulla MJ, Crow MK, Abrahams VM, Kaplan MJ, Salmon JE: Interferon-α and angiogenic dysregulation in pregnant lupus patients who develop preeclampsia. Arthritis Rheumatol. 2015 Apr. PMID: 25603823

Gysler SM, Mulla MJ, Stuhlman M, Sfakianaki AK, Paidas MJ, Stanwood NL, Gariepy A, Brosens JJ, Chamley LW, Abrahams VM: Vitamin D reverses aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast. Am J Reprod Immunol. 2015 Mar; 2014 Jul 29. PMID: 25070806

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. PMID: 25370166

Young OM, Tang Z, Niven-Fairchild T, Tadesse S, Krikun G, Norwitz ER, Mor G, Abrahams VM, Guller S: Toll-like receptor-mediated responses by placental Hofbauer cells (HBCs): a potential pro-inflammatory role for fetal M2 macrophages. Am J Reprod Immunol. 2015 Jan; 2014 Oct 24. PMID: 25345551

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; 2014 Nov 26. PMID: 25429091

Girard S, Heazell AE, Derricott H, Allan SM, Sibley CP, Abrahams VM, Jones RL: Circulating cytokines and alarmins associated with placental inflammation in high-risk pregnancies. Am J Reprod Immunol. 2014 Oct; 2014 May 28. PMID: 24867252

Bakaysa SL, Potter JA, Hoang M, Han CS, Guller S, Norwitz ER, Abrahams VM: Single- and double-stranded viral RNA generate distinct cytokine and antiviral responses in human fetal membranes. Mol Hum Reprod. 2014 Jul; 2014 Apr 9. PMID: 24723465

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; 2014 Feb 27. PMID: 24429216

Albert CR, Schlesinger WJ, Viall CA, Mulla MJ, Brosens JJ, Chamley LW, Abrahams VM: Effect of hydroxychloroquine on antiphospholipid antibody-induced changes in first trimester trophoblast function. Am J Reprod Immunol. 2014 Feb; 2013 Dec 11. PMID: 24325143

Krikun G, Potter JA, Abrahams VM: Human endometrial endothelial cells generate distinct inflammatory and antiviral responses to the TLR3 agonist, Poly(I:C) and the TLR8 agonist, viral ssRNA. Am J Reprod Immunol. 2013 Sep; 2013 Apr 29. PMID: 23621614

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; 2013 Jun 6. PMID: 23762324

Mulla MJ, Myrtolli K, Tadesse S, Stanwood NL, Gariepy A, Guller S, Norwitz ER, Abrahams VM: Cutting-edge report: TLR10 plays a role in mediating bacterial peptidoglycan-induced trophoblast apoptosis. Am J Reprod Immunol. 2013 May; 2012 Dec 28. PMID: 23279063

Kavathas PB, Boeras CM, Mulla MJ, Abrahams VM: Nod1, but not the ASC inflammasome, contributes to induction of IL-1β secretion in human trophoblasts after sensing of Chlamydia trachomatis. Mucosal Immunol. 2013 Mar; 2012 Jul 4. PMID: 22763410

Abrahams VM, Potter JA, Bhat G, Peltier MR, Saade G, Menon R: Bacterial modulation of human fetal membrane Toll-like receptor expression. Am J Reprod Immunol. 2013 Jan; 2012 Sep 11. PMID: 22967004

Garg M, Potter JA, Abrahams VM: Identification of microRNAs that regulate TLR2-mediated trophoblast apoptosis and inhibition of IL-6 mRNA. PLoS One. 2013; 2013 Oct 15. PMID: 24143215

Odiari EA, Mulla 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. Hum Reprod. 2012 Oct; 2012 Aug 11. PMID: 22888169

Krikun G, Trezza J, Shaw J, Rahman M, Guller S, Abrahams VM, Lockwood CJ: Lipopolysaccharide appears to activate human endometrial endothelial cells through TLR-4-dependent and TLR-4-independent mechanisms. Am J Reprod Immunol. 2012 Sep; 2012 Jun 4. PMID: 22672000

Schatz F, Kayisli UA, Vatandaslar E, Ocak N, Guller S, Abrahams VM, Krikun G, Lockwood CJ: Toll-like receptor 4 expression in decidual cells and interstitial trophoblasts across human pregnancy. Am J Reprod Immunol. 2012 Aug; 2012 May 8. PMID: 22564191

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 Jun. PMID: 22348442

Panda B, Panda A, Ueda I, Abrahams VM, Norwitz ER, Stanic AK, Young BC, Ecker JL, Altfeld M, Shaw AC, Rueda BR: Dendritic cells in the circulation of women with preeclampsia demonstrate a pro-inflammatory bias secondary to dysregulation of TLR receptors. J Reprod Immunol. 2012 Jun; 2012 Mar 21. PMID: 22440523

Holder BS, Tower CL, Abrahams VM, Aplin JD: Syncytin 1 in the human placenta. Placenta. 2012 Jun; 2012 Feb 29. PMID: 22381536

Holder BS, Tower CL, Jones CJ, Aplin JD, Abrahams VM: Heightened pro-inflammatory effect of preeclamptic placental microvesicles on peripheral blood immune cells in humans. Biol Reprod. 2012 Apr; 2012 Apr 5. PMID: 22205696

Han CS, Mulla MJ, Brosens JJ, Chamley LW, Paidas MJ, Lockwood CJ, Abrahams VM: Aspirin and heparin effect on basal and antiphospholipid antibody modulation of trophoblast function. Obstet Gynecol. 2011 Nov. PMID: 22015869

Carroll TY, Mulla MJ, Han CS, Brosens JJ, Chamley LW, Giles I, Pericleous C, Rahman A, Sfakianaki AK, Paidas MJ, Abrahams VM: Modulation of trophoblast angiogenic factor secretion by antiphospholipid antibodies is not reversed by heparin. Am J Reprod Immunol. 2011 Oct; 2011 May 4. PMID: 21545366

Tang Z, Tadesse S, Norwitz E, Mor G, Abrahams VM, Guller S: Isolation of hofbauer cells from human term placentas with high yield and purity. Am J Reprod Immunol. 2011 Oct; 2011 May 4. PMID: 21545365

Rose JA, Rabenold JJ, Parast MM, Milstone DS, Abrahams VM, Riley JK: Peptidoglycan induces necrosis and regulates cytokine production in murine trophoblast stem cells. Am J Reprod Immunol. 2011 Sep; 2011 Mar 9. PMID: 21385270

Abrahams VM: Reproductive immunology: the clinical view. Expert Rev Clin Immunol. 2011 Sep. PMID: 21895465

Cardenas I, Mulla MJ, Myrtolli K, Sfakianaki AK, Norwitz ER, Tadesse S, Guller S, Abrahams VM: Nod1 activation by bacterial iE-DAP induces maternal-fetal inflammation and preterm labor. J Immunol. 2011 Jul 15; 2011 Jun 15. PMID: 21677137

Mulla MJ, Myrtolli K, Potter J, Boeras C, Kavathas PB, Sfakianaki AK, Tadesse S, Norwitz ER, Guller S, Abrahams VM: Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol. 2011 Jun. PMID: 21352397

Toti P, Arcuri F, Tang Z, Schatz F, Zambrano E, Mor G, Niven-Fairchild T, Abrahams VM, Krikun G, Lockwood CJ, Guller S: Focal increases of fetal macrophages in placentas from pregnancies with histological chorioamnionitis: potential role of fibroblast monocyte chemotactic protein-1. Am J Reprod Immunol. 2011 May; 2010 Nov 19. PMID: 21087336

Tang Z, Abrahams VM, Mor G, Guller S: Placental Hofbauer cells and complications of pregnancy. Ann N Y Acad Sci. 2011 Mar. PMID: 21401637

Abrahams VM: The role of the Nod-like receptor family in trophoblast innate immune responses. J Reprod Immunol. 2011 Mar; 2011 Jan 31. PMID: 21277024

Shaw JL, Wills GS, Lee KF, Horner PJ, McClure MO, Abrahams VM, Wheelhouse N, Jabbour HN, Critchley HO, Entrican G, Horne AW: Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFκB activation resulting in a microenvironment predisposed to ectopic pregnancy. Am J Pathol. 2011 Jan; 2010 Dec 23. PMID: 21224062

Aldo PB, Mulla MJ, Romero R, Mor G, Abrahams VM: Viral ssRNA induces first trimester trophoblast apoptosis through an inflammatory mechanism. Am J Reprod Immunol. 2010 Jul 1; 2010 Feb 17. PMID: 20175771

Abrahams VM: Thirty years of reproductive immunology: an introduction. Am J Reprod Immunol. 2010 Jun. PMID: 20565388

Luo G, Abrahams VM, Tadesse S, Funai EF, Hodgson EJ, Gao J, Norwitz ER: Progesterone inhibits basal and TNF-alpha-induced apoptosis in fetal membranes: a novel mechanism to explain progesterone-mediated prevention of preterm birth. Reprod Sci. 2010 Jun; 2010 Apr 1. PMID: 20360593

Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, Abrahams VM: Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol. 2010 May; 2010 Feb 3. PMID: 20132164

Straszewski-Chavez SL, Abrahams VM, Aldo PB, Romero R, Mor G: AKT controls human first trimester trophoblast cell sensitivity to FAS-mediated apoptosis by regulating XIAP expression. Biol Reprod. 2010 Jan; 2009 Sep 2. PMID: 19726736

Straszewski-Chavez SL, Abrahams VM, Alvero AB, Aldo PB, Ma Y, Guller S, Romero R, Mor G: The isolation and characterization of a novel telomerase immortalized first trimester trophoblast cell line, Swan 71. Placenta. 2009 Nov; 2009 Sep 18. PMID: 19766308

Abrahams VM: Mechanisms of antiphospholipid antibody-associated pregnancy complications. Thromb Res. 2009 Nov; 2009 Aug 8. PMID: 19665761

Mulla MJ, Brosens JJ, Chamley LW, Giles I, Pericleous C, Rahman A, Joyce SK, Panda B, Paidas MJ, Abrahams VM: Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am J Reprod Immunol. 2009 Aug. PMID: 19614626

Hutchinson ES, Brownbill P, Jones NW, Abrahams VM, Baker PN, Sibley CP, Crocker IP: Utero-placental haemodynamics in the pathogenesis of pre-eclampsia. Placenta. 2009 Jul; 2009 Jun 3. PMID: 19497617

Mulla MJ, Yu AG, Cardenas I, Guller S, Panda B, Abrahams VM: Regulation of Nod1 and Nod2 in first trimester trophoblast cells. Am J Reprod Immunol. 2009 Apr. PMID: 19260860

de la Torre E, Mulla MJ, Yu AG, Lee SJ, Kavathas PB, Abrahams VM: Chlamydia trachomatis infection modulates trophoblast cytokine/chemokine production. J Immunol. 2009 Mar 15. PMID: 19265152

Koga K, Cardenas I, Aldo P, Abrahams VM, Peng B, Fill S, Romero R, Mor G: Activation of TLR3 in the trophoblast is associated with preterm delivery. Am J Reprod Immunol. 2009 Mar. PMID: 19239422

Abrahams VM, Aldo PB, Murphy SP, Visintin I, Koga K, Wilson G, Romero R, Sharma S, Mor G: TLR6 modulates first trimester trophoblast responses to peptidoglycan. J Immunol. 2008 May 1. PMID: 18424724

Guller S, Ma YY, Fu HH, Krikun G, Abrahams VM, Mor G: The placental syncytium and the pathophysiology of preeclampsia and intrauterine growth restriction: a novel assay to assess syncytial protein expression. Ann N Y Acad Sci. 2008 Apr. PMID: 18443340

Huang SJ, Chen CP, Schatz F, Rahman M, Abrahams VM, Lockwood CJ: Pre-eclampsia is associated with dendritic cell recruitment into the uterine decidua. J Pathol. 2008 Feb. PMID: 18069648

Abrahams VM: Antagonizing toll-like receptors to prevent preterm labor. Reprod Sci. 2008 Feb. PMID: 18276947

Abrahams VM: Pattern recognition at the maternal-fetal interface. Immunol Invest. 2008. PMID: 18716932

Ma Y, Krikun G, Abrahams VM, Mor G, Guller S: Cell type-specific expression and function of toll-like receptors 2 and 4 in human placenta: implications in fetal infection. Placenta. 2007 Oct; 2007 Jun 22. PMID: 17588655

Krikun G, Lockwood CJ, Abrahams VM, Mor G, Paidas M, Guller S: Expression of Toll-like receptors in the human decidua. Histol Histopathol. 2007 Aug. PMID: 17503341

Costello MJ, Joyce SK, Abrahams VM: NOD protein expression and function in first trimester trophoblast cells. Am J Reprod Immunol. 2007 Jan. PMID: 17156193

Fest S, Aldo PB, Abrahams VM, Visintin I, Alvero A, Chen R, Chavez SL, Romero R, Mor G: Trophoblast-macrophage interactions: a regulatory network for the protection of pregnancy. Am J Reprod Immunol. 2007 Jan. PMID: 17156192

Huang SJ, Schatz F, Masch R, Rahman M, Buchwalder L, Niven-Fairchild T, Tang C, Abrahams VM, Krikun G, Lockwood CJ: Regulation of chemokine production in response to pro-inflammatory cytokines in first trimester decidual cells. J Reprod Immunol. 2006 Dec; 2006 Jun 27. PMID: 16806486

Abrahams VM, Schaefer TM, Fahey JV, Visintin I, Wright JA, Aldo PB, Romero R, Wira CR, Mor G: Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C). Hum Reprod. 2006 Sep; 2006 Jun 3. PMID: 16751646

Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, Visintin I, Rutherford T, Mor G: TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006 Apr 1. PMID: 16585214

Hills FA, Abrahams VM, González-Timón B, Francis J, Cloke B, Hinkson L, Rai R, Mor G, Regan L, Sullivan M, Lam EW, Brosens JJ: Heparin prevents programmed cell death in human trophoblast. Mol Hum Reprod. 2006 Apr; 2006 Mar 23. PMID: 16556679

Ma Y, Mor G, Abrahams VM, Buhimschi IA, Buhimschi CS, Guller S: Alterations in syncytiotrophoblast cytokine expression following treatment with lipopolysaccharide. Am J Reprod Immunol. 2006 Jan. PMID: 16364007

Mor G, Straszewski-Chavez SL, Abrahams VM: Macrophage-trophoblast interactions. Methods Mol Med. 2006. PMID: 16511980

Abrahams VM, Visintin I, Aldo PB, Guller S, Romero R, Mor G: A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells. J Immunol. 2005 Dec 15. PMID: 16339547

Straszewski-Chavez SL, Abrahams VM, Mor G: The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy. Endocr Rev. 2005 Dec; 2005 May 18. PMID: 15901666

Kim YM, Romero R, Oh SY, Kim CJ, Kilburn BA, Armant DR, Nien JK, Gomez R, Mazor M, Saito S, Abrahams VM, Mor G: Toll-like receptor 4: a potential link between "danger signals," the innate immune system, and preeclampsia? Am J Obstet Gynecol. 2005 Sep. PMID: 16157088

Abrahams VM, Mor G: Toll-like receptors and their role in the trophoblast. Placenta. 2005 Aug. PMID: 15993703

Mor G, Romero R, Aldo PB, Abrahams VM: Is the trophoblast an immune regulator? The role of Toll-like receptors during pregnancy. Crit Rev Immunol. 2005. PMID: 16167887

Kim YM, Romero R, Chaiworapongsa T, Kim GJ, Kim MR, Kuivaniemi H, Tromp G, Espinoza J, Bujold E, Abrahams VM, Mor G: Toll-like receptor-2 and -4 in the chorioamniotic membranes in spontaneous labor at term and in preterm parturition that are associated with chorioamnionitis. Am J Obstet Gynecol. 2004 Oct. PMID: 15507964

Abrahams VM, Bole-Aldo P, Kim YM, Straszewski-Chavez SL, Chaiworapongsa T, Romero R, Mor G: Divergent trophoblast responses to bacterial products mediated by TLRs. J Immunol. 2004 Oct 1. PMID: 15383557

Abrahams VM, Kim YM, Straszewski SL, Romero R, Mor G: Macrophages and apoptotic cell clearance during pregnancy. Am J Reprod Immunol. 2004 Apr. PMID: 15212680

Abrahams VM, Straszewski-Chavez SL, Guller S, Mor G: First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod. 2004 Jan. PMID: 14665707

Straszewski-Chavez SL, Abrahams VM, Funai EF, Mor G: X-linked inhibitor of apoptosis (XIAP) confers human trophoblast cell resistance to Fas-mediated apoptosis. Mol Hum Reprod. 2004 Jan. PMID: 14665704

Mor G, Abrahams VM: Potential role of macrophages as immunoregulators of pregnancy. Reprod Biol Endocrinol. 2003 Dec 2; 2003 Dec 2. PMID: 14651752

Abrahams VM, Collins JE, Wira CR, Fanger MW, Yeaman GR: Inhibition of human polymorphonuclear cell oxidative burst by 17-beta-estradiol and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Am J Reprod Immunol. 2003 Dec. PMID: 14750553

Abrahams VM, Straszewski SL, Kamsteeg M, Hanczaruk B, Schwartz PE, Rutherford TJ, Mor G: Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res. 2003 Sep 1. PMID: 14500397

Abrahams VM, Kamsteeg M, Mor G: The Fas/Fas ligand system and cancer: immune privilege and apoptosis. Mol Biotechnol. 2003 Sep. PMID: 13679631

Mor G, Sapi E, Abrahams VM, Rutherford T, Song J, Hao XY, Muzaffar S, Kohen F: Interaction of the estrogen receptors with the Fas ligand promoter in human monocytes. J Immunol. 2003 Jan 1. PMID: 12496390

Wira CR, Fahey JV, Abrahams VM, Rossoll RM: Influence of stage of the reproductive cycle and estradiol on thymus cell antigen presentation. J Steroid Biochem Mol Biol. 2003 Jan. PMID: 12648527

Edwards JC, Cambridge G, Abrahams VM: Do self-perpetuating B lymphocytes drive human autoimmune disease? Immunology. 1999 Jun. PMID: 10447731