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 »

2009
Choi, J.C.; Holtz, R.; Murphy, S.P. "Histone deacetylases inhibit IFN-y-inducible gene expression in mouse trophoblast cells". J Immunol. 2009; 182(10): 6307-6315.
2009
Apps, R.A.; Murphy, S.P.; Fernando, R.; Gardner, L.; Ahad, T.; Moffett, A. "Human Leukocyte Antigen (HLA) expression by normal trophoblast cells and placental cell lines using a novel method to characterize allotype specificities of anti-HLA antibodies". Immunology. 2009; 127(1): 26-39.
2009
Rimsza, L.M.; Chan, W.C.; Gascoyne, R.D.; Campo, E.; Jaffe, E.S.; Staudt, L.M.; Delabie, J.; Rosenwald, A.; Murphy S.P. "CIITA or RFX Coding Region Loss of Function Mutations Occur Rarely in Diffuse Large B Cell Lymphoma Cases and Cell Lines with Low Levels of Major Histocompatibility Complex Class II Expression." Haematologica. 2009; 94(4): 596-598.
2009
Murphy, S.P.; Tayade, C.; Ashkar, A.A.; Hattta, K.; Zhang, J.; Croy B.A. "Interferon-gamma in successful pregnancies". Biol Reprod. 2009; 80(5): 848-859.
2009
Cycon, K.; Clements, J; Holtz, R.; Fuji, H.; Murphy, S.P. "The immunogenicity of L1210 lymphoma clones correlates with the ability to function as antigen presenting cells". Immunology. 2009; 128: e641-651.

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