Shawn P. Murphy, Ph.D.

Shawn P. Murphy, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 668
Rochester, NY 14642

Research Bio

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.

Awards & Honors (Local)

3rd Annual Human Placenta Workshop Lecturer 2008
Guest editor, special edition of Immunological Investigations on Reproductive Immunology 2008
2nd Annual Human Placenta Workshop Lecturer 2007
1st Annual Human Placenta Workshop Lecturer 2006
Semi-finalist, Western New York Inventor of the Year 2002
Olympus Award for New Investigators, European Placenta Group Meeting, Schladming, Austria 1999
Best Student Poster Presentation, 17th Annual Southeastern Development Biology Conference, Columbia, SC 1984

Recent Journal Articles

Showing the 5 most recent journal articles. 32 available »

2014 May 15
Gerber SA, Lim JY, Connolly KA, Sedlacek AL, Barlow ML, Murphy SP, Egilmez NK, Lord EM. "Radio-responsive tumors exhibit greater intratumoral immune activity than nonresponsive tumors." International journal of cancer. Journal international du cancer. 2014 May 15; 134(10):2383-92. Epub 2013 Nov 11.
2014 May
Bushway ME, Gerber SA, Fenton BM, Miller RK, Lord EM, Murphy SP. "Morphological and phenotypic analyses of the human placenta using whole mount immunofluorescence." Biology of reproduction. 2014 May; 90(5):110. Epub 2014 Mar 19.
2014 Mar
Lim JY, Gerber SA, Murphy SP, Lord EM. "Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells." Cancer immunology, immunotherapy : CII. 2014 Mar; 63(3):259-71. Epub 2013 Dec 20.
2013 Oct
Cycon KA, Mulvaney K, Rimsza LM, Persky D, Murphy SP. "Histone deacetylase inhibitors activate CIITA and MHC class II antigen expression in diffuse large B-cell lymphoma." Immunology. 2013 Oct; 140(2):259-72.
2013 Jun
Gerber SA, Sedlacek AL, Cron KR, Murphy SP, Frelinger JG, Lord EM. "IFN-? mediates the antitumor effects of radiation therapy in a murine colon tumor." The American journal of pathology. 2013 Jun; 182(6):2345-54. Epub 2013 Apr 12.

Current Appointments

Associate Professor - Department of Obstetrics and Gynecology (SMD) - Primary
Associate Professor - Department of Microbiology and Immunology (SMD)

Education

PhD | Microbiology | Duke University1989
BA | Biology | New College1983

Post-Doctoral Training & Residency

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