Our research focuses on understanding how transcription factors modulate lineage differentiation and function of immune subsets.
“To be or not to be…”
Development of hematopoietic cells occurs in the primary lymphoid organs and requires a complex transcriptional network that promotes the progression from an uncommitted self-renewing stem cell progenitor to a mature cell. Upon achievement of a mature state, the genomic landscape as well as the transcriptional profile of each subset will define its functional properties.
Dendritic cells (DC)
Dendritic cells are key players of the immune system. In peripheral tissues DCs capture antigens and present it to T cells. During infections or inflammation DCs initiate and orchestrate adaptive immunity by recognizing pathogens, secreting cytokines and shaping the appropriate inflammatory milieu. Our group is studying the different DC subsets: how they develop and how they function under steady state as well as under inflammatory conditions.
Early hematopoietic lineage commitment
The first choice during lineage commitment appears to split myeloid from lymphoid development. However increasing evidence suggests that lympho-myeloid diversification is not as restrictive. An unexpected heterogeneity characterizes mature subsets. We aim to understand how lymphoid and myeloid commitment is transcriptionally defined and whether the lineage of origin translates into specialized functional properties across different subsets.
Roxane Tussiwand graduated with a degree in biology from the University of Milan where she studied childhood leukemia. In 2006 she was sponsored by the Italian government to pursue her PhD in molecular medicine at the Institute for Research in Biomedicine in Bellinzona, Switzerland where she studied dendritic cell development. Following a postdoc with A.Rolink at the University of Basel she joined Ken Murphy’s group at Washington University where she investigated transcriptional regulation of dendritic cell development. Since 2014, she has been an assistant professor at the University of Basel in Switzerland and has recently joined the NIH as a Stadtman Investigator.
Rodrigues PF, Alberti-Servera L, Eremin A, Grajales-Reyes GE, Ivanek R, Tussiwand R. Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells. Nat Immunol. 2018
B Everts, R Tussiwand, KF. Fairfax, SC C Huang, AM Smith, CM O’Neill, WY Lam, BT Edelson, KM Murphy and EJ Pearce. Migratory CD103+ Dendritic Cells suppress Helminth-driven Type 2 Immunity Through Constitutive Expression of IL-12. J Exp Med 2016
Grajales-Reyes GE, Iwata A, Albring J, Wu X, Tussiwand R, Kc W, Kretzer NM, Briseño CG, Durai V, Bagadia P, Haldar M, Schönheit J, Rosenbauer F, Murphy TL, Murphy KM. Batf3 maintains autoactivation of Irf8 for commitment of a CD8α(+) conventional DC clonogenic progenitor. Nat Immunol. 2015
R Tussiwand, B Everts, G E Grajales-Reyes, NM Kretzer, A Iwata, J Bagaitkar, X Wu, R Wong, TL Murphy, EJ Pearce, KM Murphy. KLF4 expression in conventional dendritic cells is required for T helper 2 responses. Immunity 2015
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. Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature 2012
Theresa L. Murphy, Gary E. Grajales-Reyes, Xiaodi Wu, Roxane Tussiwand, Carlos G. Briseño, Arifumi Iwata, Nicole M. Kretzer, Vivek Durai, and Kenneth M. Murphy. Transcriptional Control of Dendritic Cell Development. Annu. Rev. Immunol 2016