Shawn P. Murphy, Ph.D.

Dr. Murphy received his bachelor’s degree in Biology/Chemistry from New College of U.S.F. in 1983. He subsequently earned his Ph.D. from the Department of Microbiology and Immunology at Duke University in 1989, and pursued a post-doctoral fellowship in the Department of Biochemistry, Molecular Biology and Cellular Biology at Northwestern University from 1989-1993.

One of the long term goals of our research is to determine why the maternal immune system does not reject the semi-allogeneic fetus during pregnancy. The absence of major histocompatibility complex (MHC) class II antigen expression on fetally-derived trophoblast cells of the placenta is thought to be critical for prevention of deleterious maternal immune responses against the fetus. Trophoblast cells are unique because they do not express MHC class II antigens, either constitutively, or after exposure to IFN-γ. 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-γ treatment results from silencing of expression of the class II transactivator (CIITA), a transacting transcription factor essential for constitutive and IFN-γ-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-γ is due to at least two overlapping mechanisms: 1) suboptimal ability to respond to IFN-γ, and 2) a repressive chromatin structure at the CIITA promoter.

A second project in the laboratory is based on previous studies by Dr. Lisa Rimsza and colleagues at the University of Arizona, who recently demonstrated that loss of MHC class II expression on diffuse large B cell lymphoma (DLBLCL) is associated with a significant decrease in patient survival.   Our recent studies in collaboration with Dr. Rimsza’s group demonstrate that multiple distinct mechanisms account for down-regulation of MHC class II expression in DLBCL, including silencing of CIITA expression. Thus, we are also currently examining the molecular mechanisms responsible for silencing CIITA in DLBCL.

How to contact Dr. Murphy:

E-mail address: shawn_murphy@urmc.rochester.edu

Selected Publications:

• Choi, J.C., Petroff, M.G., Holtz, R., Alfaidy, N., and Murphy, S.P. Dampening of IFN-?-inducible gene expression in human choriocarcinoma cells is due to phosphatase-mediated inhibition of the JAK/STAT-1 pathway. J. Immunol. 178:1598-1607, 2007.
• Cycon, K., Roberts, R., Rimsza, L., and Murphy, S.P.  Multiple distinct mechanisms account for the down-regulation of MHC class II gene expression in diffuse large B cell lymphoma.  in preparation.
• Choi, J.C., Holtz, R., and Murphy, S.P. IFN-γ-inducible gene transcription is dampened in mouse trophoblast cells. submitted.
• Cycon, K., Clements, J., Holtz, R., Fuji, H., and Murphy, S.P. The immunogenicity of L1210 lymphoma clones correlates with the ability to function as antigen presenting cells. in preparation.Murphy, S.P., Choi, J.C., and Holtz, R. Regulation of major histocompatibility complex class II expression in trophoblast cells. Reprod. Biol. Endocrinol., 2(1):52-59, 2004.
• Chang, C.-C., Murphy, S.P., and Ferrone, S. Differential in vivo and in vitro HLA-G expression in melanoma cells: potential mechanisms. Human Immunology, 64:1057-1063, 2003.
• Holtz, R., Choi, J., Petroff, M.G., Piskurich, J.F. and Murphy, S.P. CIITA promoter methylation does notcorrelate with silencing of CIITA transcription in trophoblasts. Biol. Reprod. 69:915-924, 2003.Murphy, S.P., Holtz, R., Lewandowski, N., Tomasi, T.B. and Fuji, H. DNA alkylating agents alleviate silencing of CIITA gene expression in L1210 lymphoma cells. J. Immunol. 169:3085-
  3093, 2002.
• Li, L.H., Sen, A., Murphy, S.P., Jahreis, G.P., Fuji, H. and Hui, S.W. DNA uptake induces apoptosis and limits transfection efficiency in select subclones of 1210. Exp. Cell Res. 253:541-550, 1999.
• Murphy, S.P. and Tomasi, T.B. The absence ofMHC class II antigen expression in trophoblast cells results from a lack of class II transactivator (CIITA) gene expression. Mol. Reprod. Dev. 51:1-12, 1998.

Updated November 8, 2007