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Shawn P. Murphy, Ph.D.

Shawn P. Murphy, Ph.D.

Contact

Office (585) 273-3910

About Me

Faculty Appointments

Associate Professor - Department of Obstetrics and Gynecology (SMD)

Associate Professor - Department of Microbiology and Immunology (SMD) - Joint

Credentials

Post-doctoral Training & Residency

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

Education

PhD | Duke University. Microbiology. 1989

BA | New College. Biology. 1983

Awards

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

Research

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 ...
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.

Publications

Journal Articles

Single-cell RNA sequencing reveals placental response under environmental stress.

Van Buren E, Azzara D, Rangel-Moreno J, Garcia-Hernandez ML, Murphy SP, Cohen ED, Lewis E, Lin X, Park HR

Nature communications.. 2024 August 215 (1):6549. Epub 08/02/2024.

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.

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

Cell death & disease.. 2023 July 2614 (7):470. Epub 07/26/2023.

Roles of natural resistance-associated macrophage protein-1 in modulating bacterial distribution and immune responses during Salmonella enterica serovar Typhimurium infection in murine pregnancy.

Agbayani G, Clark K, Sad S, Murphy SP, Krishnan L

American journal of reproductive immunology : AJRI.. 2022 October 88 (4):e13599. Epub 08/23/2022.

Characterization of the temporal, cell-specific and interferon-inducible patterns of indoleamine 2,3 dioxygenase 1 (IDO1) expression in the human placenta across gestation.

Murthy GG, Prideaux MA, Armstrong M, Kenney HM, Latchney SE, Susiarjo M, Murphy SP

Placenta.. 2021 November 115 :129-138. Epub 09/14/2021.

IFN-alpha receptor deficiency enhances host resistance to oral Salmonella enterica serovar Typhimurium infection during murine pregnancy.

Agbayani G, Clark K, Sandhu JK, Hewitt M, Sad S, Murphy SP, Krishnan L

American journal of reproductive immunology : AJRI.. 2021 October 86 (4):e13454. Epub 05/29/2021.

Analysis of the capacity of Salmonella enterica Typhimurium to infect the human Placenta.

Perry ID, Nguyen T, Sherina V, Love TMT, Miller RK, Krishnan L, Murphy SP

Placenta.. 2019 August 83 :43-52. Epub 06/26/2019.

Identification of the novel Ido1 imprinted locus and its potential epigenetic role in pregnancy loss.

Spinelli P, Latchney SE, Reed JM, Fields A, Baier BS, Lu X, McCall MN, Murphy SP, Mak W, Susiarjo M

Human molecular genetics.. 2019 February 1528 (4):662-674. Epub 1900 01 01.

Type I interferons differentially modulate maternal host immunity to infection by Listeria monocytogenes and Salmonella enterica serovar Typhimurium during pregnancy.

Agbayani G, Wachholz K, Murphy SP, Sad S, Krishnan L

American journal of reproductive immunology : AJRI.. 2019 January 81 (1):e13068. Epub 12/04/2018.

SLC11A1 is expressed in the human placenta across multiple gestational ages.

Perry ID, Krishnan L, Murphy SP

Placenta.. 2019 January 75 :23-26. Epub 11/22/2018.

Modulation of Th17 and regulatory T-cell responses during murine pregnancy contributes to increased maternal susceptibility to Salmonella Typhimurium infection.

Agbayani G, Wachholz K, Chattopadhyay A, Gurnani K, Murphy SP, Krishnan L

American journal of reproductive immunology : AJRI.. 2017 December 78 (6)Epub 10/09/2017.

Optimized logic rules reveal interferon-?-induced modes regulated by histone deacetylases and protein tyrosine phosphatases.

Van Twisk D, Murphy SP, Thakar J

Immunology.. 2017 May 151 (1):71-80. Epub 02/09/2017.

Whole mount immunofluorescence analysis of placentas from normotensive versus preeclamptic pregnancies.

Zozzaro-Smith PE, Bushway ME, Gerber SA, Hebert D, Pressman EK, Lord EM, Miller RK, Murphy SP

Placenta.. 2015 November 36 (11):1310-7. Epub 09/10/2015.

Radio-responsive tumors exhibit greater intratumoral immune activity than nonresponsive tumors.

Gerber SA, Lim JY, Connolly KA, Sedlacek AL, Barlow ML, Murphy SP, Egilmez NK, Lord EM

International journal of cancer.. 2014 May 15134 (10):2383-92. Epub 11/11/2013.

Morphological and phenotypic analyses of the human placenta using whole mount immunofluorescence.

Bushway ME, Gerber SA, Fenton BM, Miller RK, Lord EM, Murphy SP

Biology of reproduction.. 2014 May 90 (5):110. Epub 03/19/2014.

Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells.

Lim JY, Gerber SA, Murphy SP, Lord EM

Cancer immunology, immunotherapy : CII.. 2014 March 63 (3):259-71. Epub 12/20/2013.

Histone deacetylase inhibitors activate CIITA and MHC class II antigen expression in diffuse large B-cell lymphoma.

Cycon KA, Mulvaney K, Rimsza LM, Persky D, Murphy SP

Immunology.. 2013 October 140 (2):259-72. Epub 1900 01 01.

IFN-? mediates the antitumor effects of radiation therapy in a murine colon tumor.

Gerber SA, Sedlacek AL, Cron KR, Murphy SP, Frelinger JG, Lord EM

The American journal of pathology.. 2013 June 182 (6):2345-54. Epub 04/12/2013.

Immunohistochemical analysis reveals an influx of regulatory T cells and focal trophoblastic STAT-1 phosphorylation in chronic villitis of unknown etiology.

Katzman PJ, Shawn M, Oble D

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.. 2011 14 (4):284-93. Epub 02/23/2011.

Coordinate loss of MHC class II expression in the diffuse large B cell lymphoma cell line OCI-Ly2 is due to a novel mutation in RFX-AP.

Bushway M, Cycon KA, Mulvaney K, Murphy SP

Immunogenetics.. 2010 February 62 (2):109-16. Epub 12/19/2009.

Interferon gamma in successful pregnancies.

Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Croy BA

Biology of reproduction.. 2009 May 80 (5):848-59. Epub 01/21/2009.

Choi, J.C.; Holtz, R.; Murphy, S.P.

Histone deacetylases inhibit IFN-y-inducible

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

Apps, R.A.; Murphy, S.P.; Fernando, R.; Gardner, L.; Ahad, T.; Moffett, A.

Immunology. 2009; 127(1): 26-39.

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.

Rimsza, L.M.; Chan, W.C.; Gascoyne, R.D.; Campo, E.; Jaffe, E.S.; Staudt, L.M.; Delabie, J.; Rosenwald, A.; Murphy S.P.

Haematologica. 2009; 94(4): 596-598.

Interferon-gamma in successful pregnancies

Murphy, S.P.; Tayade, C.; Ashkar, A.A.; Hattta, K.; Zhang, J.; Croy B.A.

Biol Reprod. 2009; 80(5): 848-859.

The immunogenicity of L1210 lymphoma clones correlates with the ability to function as antigen presenting cells

Cycon, K.; Clements, J; Holtz, R.; Fuji, H.; Murphy, S.P.

Immunology. 2009; 128: e641-651.

Alterations in CIITA constitute a common mechanism accounting for downregulation of MHC class II expression in diffuse large B cell lymphoma (DLBCL)

Cycon, K.; Rimsza, L.; Murphy, S.P.

Experimental Hematology. 2009; 37(2): 184-194.

Dampening of IFN-gamma-inducible gene expression in human choriocarcinoma cells is due to phosphatase-mediated inhibition of the JAK/STAT-1 pathway.

Choi JC, Holtz R, Petroff MG, Alfaidy N, Murphy SP

The Journal of immunology : official journal of the American Association of Immunologists.. 2007 February 1178 (3):1598-607. Epub 1900 01 01.

Dampening of IFN-y-inducible gene expression in human choriocarcinoma cells is due to phosphatase-mediated inhibition of the JAK/STAT-1 pathway

Choi, J.C.; Petroff, M.G.; Holtz, R.; Alfaidy, N.; Challis, J.R.; Murphy, S.P.

J Immunol. 2007; 178(3): 1589-1607.

Regulation of major histocompatibility complex class II gene expression in trophoblast cells.

Murphy SP, Choi JC, Holtz R

Reproductive biology and endocrinology : RB&E.. 2004 July 52 :52. Epub 07/05/2004.

Differential in vivo and in vitro HLA-G expression in melanoma cells: potential mechanisms.

Chang CC, Murphy SP, Ferrone S

Human immunology.. 2003 November 64 (11):1057-63. Epub 1900 01 01.

Class II transactivator (CIITA) promoter methylation does not correlate with silencing of CIITA transcription in trophoblasts.

Holtz R, Choi JC, Petroff MG, Piskurich JF, Murphy SP

Biology of reproduction.. 2003 September 69 (3):915-24. Epub 05/14/2003.

DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.

Murphy SP, Holtz R, Lewandowski N, Tomasi TB, Fuji H

The Journal of immunology : official journal of the American Association of Immunologists.. 2002 September 15169 (6):3085-93. Epub 1900 01 01.

Apoptosis induced by DNA uptake limits transfection efficiency.

Li LH, Sen A, Murphy SP, Jahreis GP, Fuji H, Hui SW

Experimental cell research.. 1999 December 15253 (2):541-50. Epub 1900 01 01.

Absence of MHC class II antigen expression in trophoblast cells results from a lack of class II transactivator (CIITA) gene expression.

Murphy SP, Tomasi TB

Molecular reproduction and development.. 1998 September 51 (1):1-12. Epub 1900 01 01.

Repression of MHC class II gene transcription in trophoblast cells by novel single-stranded DNA binding proteins.

Murphy SP, Gollnick SO, Pazmany T, Maier P, Elkin G, Tomasi TB

Molecular reproduction and development.. 1997 August 47 (4):390-403. Epub 1900 01 01.

Activation of multiple transcription factors and fos and jun gene family expression in cells exposed to a single electric pulse.

Pazmany T, Murphy SP, Gollnick SO, Brooks SP, Tomasi TB

Experimental cell research.. 1995 November 221 (1):103-10. Epub 1900 01 01.

Cloning and subcellular localization of human mitochondrial hsp70.

Bhattacharyya T, Karnezis AN, Murphy SP, Hoang T, Freeman BC, Phillips B, Morimoto RI

The Journal of biological chemistry.. 1995 January 27270 (4):1705-10. Epub 1900 01 01.

Deficient induction of human hsp70 heat shock gene transcription in Y79 retinoblastoma cells despite activation of heat shock factor 1.

Mathur SK, Sistonen L, Brown IR, Murphy SP, Sarge KD, Morimoto RI

Proceedings of the National Academy of Sciences of the United States of America.. 1994 August 3091 (18):8695-9. Epub 1900 01 01.

Characterization of constitutive HSF2 DNA-binding activity in mouse embryonal carcinoma cells.

Murphy SP, Gorzowski JJ, Sarge KD, Phillips B

Molecular and cellular biology.. 1994 August 14 (8):5309-17. Epub 1900 01 01.

Small subclass of olfactory neurons with specific bulbar projections reactive with monoclonal antibodies to the hsp70 heat shock protein.

Carr, V.M.; Murphy, S.P.; Morimoto, R.I.; Farbman, A.

Carr, V.M., Murphy, S.P., Morimoto, R.I. and Farbman, A. 1994; 348: 150-160.

Sarge, K.D.; Murphy, S.P.; Morimoto, R.I.

Activation of heat shock gene transcription of

Differential regulation of Heat shock gene transcription by a family of heat shock factors. (Review).

Kroeger, P.E.; Sarge, K.D.; Murphy, S.P.; Naki, A.; Morimoto, R.I.

J. Occup. Environ.

The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression.

Abravaya K, Myers MP, Murphy SP, Morimoto RI

Genes & development.. 1992 July 6 (7):1153-64. Epub 1900 01 01.

Espeseth, A.; Murphy, S.P.; Linney, E.

Retinoic acid receptor expression vector inhibits

Differential expression of the homeobox gene Hox-1.3 in F9 embryonal carcinoma cells.

Murphy SP, Garbern J, Odenwald WF, Lazzarini RA, Linney E

Proceedings of the National Academy of Sciences of the United States of America.. 1988 August 85 (15):5587-91. Epub 1900 01 01.