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Shawn P. Murphy, Ph.D.

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Faculty Appointments



One of the long term goals of our research is to determine why the maternal immune system does not reject the genetically disparate fetus during pregnancy. Our studies are focused primarily on the immunoregulatory properties of trophoblast cells, which are the first cells to differentiate from the embryo, and ultimately form the fetal component of the placenta. Trophoblast cells are the only cells derived from the blastocyst that are in direct contact with maternal blood, and therefore play an essential role in protecting the fetus from attack from the maternal immune system. Trophoblast cells are relatively unique in that they do not express major histocompatibility complex (MHC) class II antigens, either constitutively, or after exposure to IFN-gamma. The absence of MHC class II antigen expression on trophoblast cells is thought to be critical for prevention of deleterious maternal immune responses against the fetus. Thus, successful reproduction of mammals may require that MHC class II gene expression be stringently repressed in trophoblast cells. We previously demonstrated that the inability of human and rodent trophoblast cells to transcribe MHC class II genes following IFN-gamma treatment results from silencing of expression of the class II transactivator (CIITA), a transacting transcription factor essential for constitutive and IFN-gamma-inducible transcription in other cell types. We have therefore been investigating the molecular mechanisms underlying transcriptional silencing of CIITA in trophoblast cells. Our studies to date suggest that silencing of CIITA expression in trophoblast cells exposed to IFN-gamma is due to at least two overlapping mechanisms: 1) hyporesponsiveness to IFN-gamma, and 2) a repressive chromatin structure at the CIITA promoter.

Our recent studies demonstrated that responses of both human and mouse trophoblast cells to IFN-gamma are significantly reduced relative to other cell types, which correspond with both the inability to express MHC class II molecules, and resistance of trophoblast cells to IFN-gamma-mediated apoptosis and inhibition of cell proliferation. Based on the fact that a wide range of pathogens, including multiple viruses, bacteria and mycobacteria have evolved mechanisms for inhibiting cellular responses to IFN-gamma as an important mechanism of immunoevasion, we have proposed that trophoblastic suppression of IFN-gamma signaling is essential for successful pregnancy. Thus, we have been investigating how trophoblast cells inhibit IFN-gamma signaling.

Our laboratory is also examining the mechanisms accounting for loss of MHC class II antigen expression in human diffuse large B cell lymphoma (DLBLCL). Downregulation of MHC class II expression on DLBLCL is associated with significant decreases in patient survival. Our recent studies in collaboration with Dr. Lisa Rimsza's group demonstrate that the most common mechanism underlying MHC class II loss in DLBCL is silencing of CIITA expression. Thus, we are currently examining the molecular mechanisms responsible for silencing CIITA in DLBCL.



BA | New College

PhD | Duke University

Post-doctoral Training & Residency

1989 - 1993
Postdoctoral Fellow, Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL


3rd Annual Human Placenta Workshop Lecturer

Guest editor, special edition of Immunological Investigations on Reproductive Immunology

2nd Annual Human Placenta Workshop Lecturer

1st Annual Human Placenta Workshop Lecturer

Semi-finalist, Western New York Inventor of the Year

Olympus Award for New Investigators, European Placenta Group Meeting, Schladming, Austria

Best Student Poster Presentation, 17th Annual Southeastern Development Biology Conference, Columbia, SC

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Journal Articles

Uccello TP, Lesch ML, Kintzel SA, Gradzewicz LB, Lamrous L, Murphy SP, Fleming FJ, Mills BN, Murphy JD, Hughson A, Hannon G, Garrett-Larsen J, Qiu H, Drage MG, Ye J, Gavras NW, Keeley DC, Love TMT, Repasky EA, Lord EM, Linehan DC, Gerber SA. "New insights into the responder/nonresponder divide in rectal cancer: Damage-induced Type I IFNs dictate treatment efficacy and can be targeted to enhance radiotherapy." Cell death & disease.. 2023 Jul 26; 14(7):470. Epub 2023 Jul 26.

Agbayani G, Clark K, Sad S, Murphy SP, Krishnan L. "Roles of natural resistance-associated macrophage protein-1 in modulating bacterial distribution and immune responses during Salmonella enterica serovar Typhimurium infection in murine pregnancy." American journal of reproductive immunology : AJRI.. 2022 Jul 18; Epub 2022 Jul 18.

Murthy GG, Prideaux MA, Armstrong M, Kenney HM, Latchney SE, Susiarjo M, Murphy SP. "Characterization of the temporal, cell-specific and interferon-inducible patterns of indoleamine 2,3 dioxygenase 1 (IDO1) expression in the human placenta across gestation." Placenta.. 2021 Sep 14; 115:129-138. Epub 2021 Sep 14.