Kenneth M. Murphy, M.D., Ph.D.

Eugene Opie First Centennial Professor
Pathology and Immunology
Investigator
Howard Hughes Medical Institute

Immunology Program
Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program

Research Abstract:

My laboratory examines how specialized lineages of the immune system develop to anticipate various types of infections and to generate the correct quality of immune response. Our initial focus examined the basis of CD4 T cell development into the function helper subsets, such as TH1, TH2, TH17, and so on. Our work defined the physiological basis of instructive differentiation that occurs in response to pathogens and defined the signaling pathways and transcriptional circuits involved. Our early discovery that dendritic cells and macrophages determined the direction of T cell differentiation, by their production of cytokines such as IL-12, led us to examine how myeloid cells evolved to be the decision makers for T cell differentiation in immunity. We are currently focused on defining the developmental basis for dendritic cell diversification into the functional subsets that control induction of the various types of lymphocyte effector responses. This work has practical implications for improved immunotherapy, including vaccine design. Ongoing projects can be found by reading our recently published work and review articles.

Selected Publications:

Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, Murphy KM. (2008) Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science ;322(5904):1097-100. PMCID:PMC2756611

Kohyama M, Ise W, Edelson BT, Wilker PR, Hildner K, Mejia C, Frazier WA, Murphy TL, Murphy KM. (2009) Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis. Nature ;457(7227):318-21. PMCID:PMC2756102

Schraml BU, Hildner K, Ise W, Lee WL, Smith WA, Solomon B, Sahota G, Sim J, Mukasa R, Cemerski S, Hatton RD, Stormo GD, Weaver CT, Russell JH, Murphy TL, Murphy KM. (2009) The AP-1 transcription factor Batf controls T(H)17 differentiation. Nature ;460(7253):405-9. PMCID:PMC2716014

Ise W, Kohyama M, Nutsch KM, Lee HM, Suri A, Unanue ER, Murphy TL, Murphy KM. (2010) CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms. Nat.Immunol.11(2):129-35. PMCID:PMC3235641

Ise W, Kohyama M, Schraml BU, Zhang T, Schwer B, Basu U, Alt FW, Tang J, Oltz EM, Murphy TL, Murphy KM. (2011) The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells. Nat.Immunol.12(6):536-43. PMCID:PMC3117275

Satpathy AT, Wu X, Albring JC, Murphy KM. (2012) Re(de)fining the dendritic cell lineage. Nat.Immunol.13(12):1145-54. PMCID:PMC3644874

Tussiwand R, Lee WL, Murphy TL, Mashayekhi M, Wumesh KC, Albring JC, Satpathy AT, Rotondo JA, Edelson BT, Kretzer NM, Wu X, Weiss LA, Glasmacher E, Li P, Liao W, Behnke M, Lam SS, Aurthur CT, Leonard WJ, Singh H, Stallings CL, Sibley LD, Schreiber RD, Murphy KM. (2012) Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature ;490(7421):502-7. PMCID:PMC3482832

Murphy TL, Tussiwand R, Murphy KM. (2013) Specificity through cooperation: BATF-IRF interactions control immune-regulatory networks. Nat.Rev.Immunol.13(7):499-509. PMID:23787991

Satpathy AT, Briseno CG, Lee JS, Ng D, Manieri NA, KC W, Wu X, Thomas SR, Lee WL, Turkoz M, McDonald KG, Meredith MM, Song C, Guidos CJ, Newberry RD, Ouyang W, Murphy TL, Stappenbeck TS, Gommerman JL, Nussenzweig MC, Colonna M, Kopan R, Murphy KM. (2013) Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat.Immunol.14(9):937-48. PMCID:PMC3788683

Haldar M, Kohyama M, So AY, KC W, Wu X, Briseno CG, Satpathy AT, Kretzer NM, Arase H, Rajasekaran NS, Wang L, Egawa T, Igarashi K, Baltimore D, Murphy TL, Murphy KM. (2014) Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell ;156(6):1223-34. PMCID:PMC4010949

Wumesh KC, Satpathy AT, Rapaport AS, Briseno CG, Wu X, Albring JC, Russler-Germain EV, Kretzer NM, Durai V, Persaud SP, Edelson BT, Loschko J, Cella M, Allen PM, Nussenzweig MC, Colonna M, Sleckman BP, Murphy TL, Murphy KM. (2014) L-Myc expression by dendritic cells is required for optimal T-cell priming. Nature ;507(7491):243-7. PMCID:PMC3954917

Last Updated: 8/5/2014 3:52:28 PM

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