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


Abrahams, Vikki M

Principal Investigator

Associate Professor of Obstetrics, Gynecology, and Reproductive Sciences

Cross, Sarah Newbold

Instructor in Obstetrics, Gynecology, and Reproductive Sciences

Gysler, Stefan

Medical Student

Martin, Nicole

Undergraduate Student

Publications

Young OM, Tang Z, Niven-Fairchild T, Tadesse S, Krikun G, Norwitz ER, Mor G, Abrahams VM and 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. 2014 Oct 24; Epub 2014 Oct 24. PMID: 25345551


Girard S, Heazell AE, Derricott H, Allan SM, Sibley CP, Abrahams VM and Jones RL: Circulating cytokines and alarmins associated with placental inflammation in high-risk pregnancies. Am J Reprod Immunol. 2014 Oct;72 (4) :422-34. Epub 2014 May 28. PMID: 24867252


Gysler SM, Mulla MJ, Stuhlman M, Sfakianaki AK, Paidas MJ, Stanwood NL, Gariepy A, Brosens JJ, Chamley LW and Abrahams VM: Vitamin D Reverses aPL-induced Inflammation and LMWH-induced sFlt-1 Release by Human Trophoblast. Am J Reprod Immunol. 2014 Jul 29; Epub 2014 Jul 29. PMID: 25070806


Bakaysa SL, Potter JA, Hoang M, Han CS, Guller S, Norwitz ER and Abrahams VM: Single- and double-stranded viral RNA generate distinct cytokine and antiviral responses in human fetal membranes. Mol Hum Reprod. 2014 Jul;20 (7) :701-8. Epub 2014 Apr 9. PMID: 24723465


Hoang M, Potter JA, Gysler SM, Han CS, Guller S, Norwitz ER and 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;90 (2) :39. Epub 2014 Feb 27. PMID: 24429216


Albert CR, Schlesinger WJ, Viall CA, Mulla MJ, Brosens JJ, Chamley LW and Abrahams VM: Effect of hydroxychloroquine on antiphospholipid antibody-induced changes in first trimester trophoblast function. Am J Reprod Immunol. 2014 Feb;71 (2) :154-64. Epub 2013 Dec 11. PMID: 24325143

Krikun G, Potter JA and 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;70 (3) :190-8. Epub 2013 Apr 29. PMID: 23621614


Mulla MJ, Salmon JE, Chamley LW, Brosens JJ, Boeras CM, Kavathas PB and 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;8 (6) :e65237. Epub 2013 Jun 6. PMID: 23762324


Mulla MJ, Myrtolli K, Tadesse S, Stanwood NL, Gariepy A, Guller S, Norwitz ER and Abrahams VM: Cutting-edge report: TLR10 plays a role in mediating bacterial peptidoglycan-induced trophoblast apoptosis. Am J Reprod Immunol. 2013 May;69 (5) :449-53. Epub 2012 Dec 28. PMID: 23279063


Kavathas PB, Boeras CM, Mulla MJ and 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;6 (2) :235-43. Epub 2012 Jul 4. PMID: 22763410


Abrahams VM, Potter JA, Bhat G, Peltier MR, Saade G and Menon R: Bacterial modulation of human fetal membrane Toll-like receptor expression. Am J Reprod Immunol. 2013 Jan;69 (1) :33-40. Epub 2012 Sep 11. PMID: 22967004


Garg M, Potter JA and Abrahams VM: Identification of microRNAs that regulate TLR2-mediated trophoblast apoptosis and inhibition of IL-6 mRNA. PLoS One. 2013;8 (10) :e77249. Epub 2013 Oct 15. PMID: 24143215

Odiari EA, Mulla MJ, Sfakianaki AK, Paidas MJ, Stanwood NL, Gariepy A, Brosens JJ, Chamley LW and Abrahams VM: Pravastatin does not prevent antiphospholipid antibody-mediated changes in human first trimester trophoblast function. Hum Reprod. 2012 Oct;27 (10) :2933-40. Epub 2012 Aug 11. PMID: 22888169


Krikun G, Trezza J, Shaw J, Rahman M, Guller S, Abrahams VM and 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;68 (3) :233-7. Epub 2012 Jun 4. PMID: 22672000


Schatz F, Kayisli UA, Vatandaslar E, Ocak N, Guller S, Abrahams VM, Krikun G and Lockwood CJ: Toll-like receptor 4 expression in decidual cells and interstitial trophoblasts across human pregnancy. Am J Reprod Immunol. 2012 Aug;68 (2) :146-53. Epub 2012 May 8. PMID: 22564191


Holder BS, Tower CL, Forbes K, Mulla MJ, Aplin JD and Abrahams VM: Immune cell activation by trophoblast-derived microvesicles is mediated by syncytin 1. Immunology. 2012 Jun;136 (2) :184-91. PMID: 22348442


Panda B, Panda A, Ueda I, Abrahams VM, Norwitz ER, Stanic AK, Young BC, Ecker JL, Altfeld M, Shaw AC and 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;94 (2) :210-5. Epub 2012 Mar 21. PMID: 22440523


Holder BS, Tower CL, Abrahams VM and Aplin JD: Syncytin 1 in the human placenta. Placenta. 2012 Jun;33 (6) :460-6. Epub 2012 Feb 29. PMID: 22381536


Holder BS, Tower CL, Jones CJ, Aplin JD and Abrahams VM: Heightened pro-inflammatory effect of preeclamptic placental microvesicles on peripheral blood immune cells in humans. Biol Reprod. 2012 Apr;86 (4) :103. Epub 2012 Apr 5. PMID: 22205696

Han CS, Mulla MJ, Brosens JJ, Chamley LW, Paidas MJ, Lockwood CJ and Abrahams VM: Aspirin and heparin effect on basal and antiphospholipid antibody modulation of trophoblast function. Obstet Gynecol. 2011 Nov;118 (5) :1021-8. PMID: 22015869


Carroll TY, Mulla MJ, Han CS, Brosens JJ, Chamley LW, Giles I, Pericleous C, Rahman A, Sfakianaki AK, Paidas MJ and Abrahams VM: Modulation of trophoblast angiogenic factor secretion by antiphospholipid antibodies is not reversed by heparin. Am J Reprod Immunol. 2011 Oct;66 (4) :286-96. Epub 2011 May 4. PMID: 21545366


Tang Z, Tadesse S, Norwitz E, Mor G, Abrahams VM and Guller S: Isolation of hofbauer cells from human term placentas with high yield and purity. Am J Reprod Immunol. 2011 Oct;66 (4) :336-48. Epub 2011 May 4. PMID: 21545365


Rose JA, Rabenold JJ, Parast MM, Milstone DS, Abrahams VM and Riley JK: Peptidoglycan induces necrosis and regulates cytokine production in murine trophoblast stem cells. Am J Reprod Immunol. 2011 Sep;66 (3) :209-22. Epub 2011 Mar 9. PMID: 21385270


Abrahams VM: Reproductive immunology: the clinical view. Expert Rev Clin Immunol. 2011 Sep;7 (5) :555-6. PMID: 21895465


Cardenas I, Mulla MJ, Myrtolli K, Sfakianaki AK, Norwitz ER, Tadesse S, Guller S and Abrahams VM: Nod1 activation by bacterial iE-DAP induces maternal-fetal inflammation and preterm labor. J Immunol. 2011 Jul 15;187 (2) :980-6. Epub 2011 Jun 15. PMID: 21677137


Mulla MJ, Myrtolli K, Potter J, Boeras C, Kavathas PB, Sfakianaki AK, Tadesse S, Norwitz ER, Guller S and Abrahams VM: Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol. 2011 Jun;65 (6) :542-8. PMID: 21352397


Toti P, Arcuri F, Tang Z, Schatz F, Zambrano E, Mor G, Niven-Fairchild T, Abrahams VM, Krikun G, Lockwood CJ and 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;65 (5) :470-9. Epub 2010 Nov 19. PMID: 21087336


Tang Z, Abrahams VM, Mor G and Guller S: Placental Hofbauer cells and complications of pregnancy. Ann N Y Acad Sci. 2011 Mar;1221 :103-8. PMID: 21401637


Abrahams VM: The role of the Nod-like receptor family in trophoblast innate immune responses. J Reprod Immunol. 2011 Mar;88 (2) :112-7. Epub 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 and 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;178 (1) :253-60. Epub 2010 Dec 23. PMID: 21224062

Aldo PB, Mulla MJ, Romero R, Mor G and Abrahams VM: Viral ssRNA induces first trimester trophoblast apoptosis through an inflammatory mechanism. Am J Reprod Immunol. 2010 Jul 1;64 (1) :27-37. Epub 2010 Feb 17. PMID: 20175771


Abrahams VM: Thirty years of reproductive immunology: an introduction. Am J Reprod Immunol. 2010 Jun;63 (6) :411-2. PMID: 20565388


Luo G, Abrahams VM, Tadesse S, Funai EF, Hodgson EJ, Gao J and 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;17 (6) :532-9. Epub 2010 Apr 1. PMID: 20360593


Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ and Abrahams VM: Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol. 2010 May;63 (5) :339-48. Epub 2010 Feb 3. PMID: 20132164


Straszewski-Chavez SL, Abrahams VM, Aldo PB, Romero R and Mor G: AKT controls human first trimester trophoblast cell sensitivity to FAS-mediated apoptosis by regulating XIAP expression. Biol Reprod. 2010 Jan;82 (1) :146-52. Epub 2009 Sep 2. PMID: 19726736

Straszewski-Chavez SL, Abrahams VM, Alvero AB, Aldo PB, Ma Y, Guller S, Romero R and Mor G: The isolation and characterization of a novel telomerase immortalized first trimester trophoblast cell line, Swan 71. Placenta. 2009 Nov;30 (11) :939-48. Epub 2009 Sep 18. PMID: 19766308


Abrahams VM: Mechanisms of antiphospholipid antibody-associated pregnancy complications. Thromb Res. 2009 Nov;124 (5) :521-5. Epub 2009 Aug 8. PMID: 19665761


Mulla MJ, Brosens JJ, Chamley LW, Giles I, Pericleous C, Rahman A, Joyce SK, Panda B, Paidas MJ and Abrahams VM: Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am J Reprod Immunol. 2009 Aug;62 (2) :96-111. PMID: 19614626


Hutchinson ES, Brownbill P, Jones NW, Abrahams VM, Baker PN, Sibley CP and Crocker IP: Utero-placental haemodynamics in the pathogenesis of pre-eclampsia. Placenta. 2009 Jul;30 (7) :634-41. Epub 2009 Jun 3. PMID: 19497617


Mulla MJ, Yu AG, Cardenas I, Guller S, Panda B and Abrahams VM: Regulation of Nod1 and Nod2 in first trimester trophoblast cells. Am J Reprod Immunol. 2009 Apr;61 (4) :294-302. PMID: 19260860


de la Torre E, Mulla MJ, Yu AG, Lee SJ, Kavathas PB and Abrahams VM: Chlamydia trachomatis infection modulates trophoblast cytokine/chemokine production. J Immunol. 2009 Mar 15;182 (6) :3735-45. PMID: 19265152


Koga K, Cardenas I, Aldo P, Abrahams VM, Peng B, Fill S, Romero R and Mor G: Activation of TLR3 in the trophoblast is associated with preterm delivery. Am J Reprod Immunol. 2009 Mar;61 (3) :196-212. PMID: 19239422

Abrahams VM, Aldo PB, Murphy SP, Visintin I, Koga K, Wilson G, Romero R, Sharma S and Mor G: TLR6 modulates first trimester trophoblast responses to peptidoglycan. J Immunol. 2008 May 1;180 (9) :6035-43. PMID: 18424724


Guller S, Ma YY, Fu HH, Krikun G, Abrahams VM and 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;1127 :129-33. PMID: 18443340


Huang SJ, Chen CP, Schatz F, Rahman M, Abrahams VM and Lockwood CJ: Pre-eclampsia is associated with dendritic cell recruitment into the uterine decidua. J Pathol. 2008 Feb;214 (3) :328-36. PMID: 18069648


Abrahams VM: Antagonizing toll-like receptors to prevent preterm labor. Reprod Sci. 2008 Feb;15 (2) :108-9. PMID: 18276947


Abrahams VM: Pattern recognition at the maternal-fetal interface. Immunol Invest. 2008;37 (5) :427-47. PMID: 18716932

Ma Y, Krikun G, Abrahams VM, Mor G and 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;28 (10) :1024-31. Epub 2007 Jun 22. PMID: 17588655


Krikun G, Lockwood CJ, Abrahams VM, Mor G, Paidas M and Guller S: Expression of Toll-like receptors in the human decidua. Histol Histopathol. 2007 Aug;22 (8) :847-54. PMID: 17503341


Costello MJ, Joyce SK and Abrahams VM: NOD protein expression and function in first trimester trophoblast cells. Am J Reprod Immunol. 2007 Jan;57 (1) :67-80. PMID: 17156193


Fest S, Aldo PB, Abrahams VM, Visintin I, Alvero A, Chen R, Chavez SL, Romero R and Mor G: Trophoblast-macrophage interactions: a regulatory network for the protection of pregnancy. Am J Reprod Immunol. 2007 Jan;57 (1) :55-66. PMID: 17156192

Huang SJ, Schatz F, Masch R, Rahman M, Buchwalder L, Niven-Fairchild T, Tang C, Abrahams VM, Krikun G and Lockwood CJ: Regulation of chemokine production in response to pro-inflammatory cytokines in first trimester decidual cells. J Reprod Immunol. 2006 Dec;72 (1-2) :60-73. Epub 2006 Jun 27. PMID: 16806486


Abrahams VM, Schaefer TM, Fahey JV, Visintin I, Wright JA, Aldo PB, Romero R, Wira CR and 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;21 (9) :2432-9. Epub 2006 Jun 3. PMID: 16751646


Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, Visintin I, Rutherford T and Mor G: TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006 Apr 1;66 (7) :3859-68. 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 and Brosens JJ: Heparin prevents programmed cell death in human trophoblast. Mol Hum Reprod. 2006 Apr;12 (4) :237-43. Epub 2006 Mar 23. PMID: 16556679


Ma Y, Mor G, Abrahams VM, Buhimschi IA, Buhimschi CS and Guller S: Alterations in syncytiotrophoblast cytokine expression following treatment with lipopolysaccharide. Am J Reprod Immunol. 2006 Jan;55 (1) :12-8. PMID: 16364007


Mor G, Straszewski-Chavez SL and Abrahams VM: Macrophage-trophoblast interactions. Methods Mol Med. 2006;122 :149-63. PMID: 16511980

Abrahams VM, Visintin I, Aldo PB, Guller S, Romero R and Mor G: A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells. J Immunol. 2005 Dec 15;175 (12) :8096-104. PMID: 16339547


Straszewski-Chavez SL, Abrahams VM and Mor G: The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy. Endocr Rev. 2005 Dec;26 (7) :877-97. Epub 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 and Mor G: Toll-like receptor 4: a potential link between "danger signals," the innate immune system, and preeclampsia? Am J Obstet Gynecol. 2005 Sep;193 (3 Pt 2) :921-7. PMID: 16157088


Abrahams VM and Mor G: Toll-like receptors and their role in the trophoblast. Placenta. 2005 Aug;26 (7) :540-7. PMID: 15993703


Mor G, Romero R, Aldo PB and Abrahams VM: Is the trophoblast an immune regulator? The role of Toll-like receptors during pregnancy. Crit Rev Immunol. 2005;25 (5) :375-88. PMID: 16167887

Kim YM, Romero R, Chaiworapongsa T, Kim GJ, Kim MR, Kuivaniemi H, Tromp G, Espinoza J, Bujold E, Abrahams VM and 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;191 (4) :1346-55. PMID: 15507964


Abrahams VM, Bole-Aldo P, Kim YM, Straszewski-Chavez SL, Chaiworapongsa T, Romero R and Mor G: Divergent trophoblast responses to bacterial products mediated by TLRs. J Immunol. 2004 Oct 1;173 (7) :4286-96. PMID: 15383557


Abrahams VM, Kim YM, Straszewski SL, Romero R and Mor G: Macrophages and apoptotic cell clearance during pregnancy. Am J Reprod Immunol. 2004 Apr;51 (4) :275-82. PMID: 15212680


Abrahams VM, Straszewski-Chavez SL, Guller S and Mor G: First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod. 2004 Jan;10 (1) :55-63. PMID: 14665707


Straszewski-Chavez SL, Abrahams VM, Funai EF and Mor G: X-linked inhibitor of apoptosis (XIAP) confers human trophoblast cell resistance to Fas-mediated apoptosis. Mol Hum Reprod. 2004 Jan;10 (1) :33-41. PMID: 14665704

Mor G and Abrahams VM: Potential role of macrophages as immunoregulators of pregnancy. Reprod Biol Endocrinol. 2003 Dec 2;1 :119. Epub 2003 Dec 2. PMID: 14651752


Abrahams VM, Collins JE, Wira CR, Fanger MW and 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;50 (6) :463-72. PMID: 14750553


Abrahams VM, Straszewski SL, Kamsteeg M, Hanczaruk B, Schwartz PE, Rutherford TJ and Mor G: Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res. 2003 Sep 1;63 (17) :5573-81. PMID: 14500397


Abrahams VM, Kamsteeg M and Mor G: The Fas/Fas ligand system and cancer: immune privilege and apoptosis. Mol Biotechnol. 2003 Sep;25 (1) :19-30. PMID: 13679631


Mor G, Sapi E, Abrahams VM, Rutherford T, Song J, Hao XY, Muzaffar S and Kohen F: Interaction of the estrogen receptors with the Fas ligand promoter in human monocytes. J Immunol. 2003 Jan 1;170 (1) :114-22. PMID: 12496390


Wira CR, Fahey JV, Abrahams VM and Rossoll RM: Influence of stage of the reproductive cycle and estradiol on thymus cell antigen presentation. J Steroid Biochem Mol Biol. 2003 Jan;84 (1) :79-87. PMID: 12648527

Abrahams VM, Cambridge G, Lydyard PM and Edwards JC: Induction of tumor necrosis factor alpha production by adhered human monocytes: a key role for Fcgamma receptor type IIIa in rheumatoid arthritis. Arthritis Rheum. 2000 Mar;43 (3) :608-16. PMID: 10728755

Edwards JC, Cambridge G and Abrahams VM: Do self-perpetuating B lymphocytes drive human autoimmune disease? Immunology. 1999 Jun;97 (2) :188-96. PMID: 10447731