Maria Ciofani

Associate Professor of Integrative Immunobiology

Transcriptional Regulation of Proinflammatory Lymphocytes

IL-17-expressing CD4 T helper (Th17) cells are important members of the intestinal immune cell community that contribute to protection against bacterial and fungal infections, and maintenance of intestinal homeostasis.  Although central to immunity, dysregulted Th17 cell function has been implicated in tissue inflammation and autoimmune disease (e.g. Inflammatory bowel disease, arthritis, and multiple sclerosis).  In order to understand this balance between healthy and pathogenic responses, we are interested in defining the transcriptional regulatory mechanisms that govern (1) Th17 cell specification from naive T cell precursors and, (2) Th17 cell effector plasticity during inflammation.  Combining genome-wide interrogation of regulatory information (transcription factor occupancy, chromatin accessibility, and transcriptional output) with gene-deficiency models in mice, we can dissect the contribution of key transcriptional regulators in proinflammatory T cell function.



We currently have open positions for students, postdoctoral fellows and a research technician.


Appointments and Affiliations

  • Associate Professor of Integrative Immunobiology
  • Associate Professor of Cell Biology
  • Member of the Duke Cancer Institute

Contact Information

  • Office Location: 128 Jones Bldg, 207 Researchr, 3010 DUMC, Durham, NC 27710
  • Email Address: maria.ciofani@duke.edu

Education

  • Ph.D. University of Toronto (Canada), 2007

Courses Taught

  • IMMUNOL 800: Comprehensive Immunology
  • IMMUNOL 736: Topics in Immunology
  • IMMUNOL 735: Topics in Immunology

In the News

Representative Publications

  • Parker, Morgan E., Alejandro Barrera, Joshua D. Wheaton, Matthew K. Zuberbuehler, David S. J. Allan, James R. Carlyle, Timothy E. Reddy, and Maria Ciofani. “c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program.” J Exp Med 217, no. 1 (January 6, 2020). https://doi.org/10.1084/jem.20191030.
  • Parker, Morgan E., and Maria Ciofani. “Regulation of γδ T Cell Effector Diversification in the Thymus.” Front Immunol 11 (2020): 42. https://doi.org/10.3389/fimmu.2020.00042.
  • Wheaton, Joshua D., and Maria Ciofani. “JunB Controls Intestinal Effector Programs in Regulatory T Cells.” Front Immunol 11 (2020): 444. https://doi.org/10.3389/fimmu.2020.00444.
  • Espinosa, Jaclyn R., Joshua D. Wheaton, and Maria Ciofani. “In Vitro Differentiation of CD4+ T Cell Effector and Regulatory Subsets.” Methods Mol Biol 2111 (2020): 79–89. https://doi.org/10.1007/978-1-0716-0266-9_7.
  • Juvvadi, Praveen R., David Fox, Benjamin G. Bobay, Michael J. Hoy, Sophie M. C. Gobeil, Ronald A. Venters, Zanetta Chang, et al. “Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents.” Nat Commun 10, no. 1 (September 19, 2019): 4275. https://doi.org/10.1038/s41467-019-12199-1.
  • Miraldi, Emily R., Maria Pokrovskii, Aaron Watters, Dayanne M. Castro, Nicholas De Veaux, Jason A. Hall, June-Yong Lee, et al. “Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.” Genome Res 29, no. 3 (March 2019): 449–63. https://doi.org/10.1101/gr.238253.118.
  • Zuberbuehler, Matthew K., Morgan E. Parker, Joshua D. Wheaton, Jaclyn R. Espinosa, Harmony R. Salzler, Eunchong Park, and Maria Ciofani. “The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells.” Nat Immunol 20, no. 1 (January 2019): 73–85. https://doi.org/10.1038/s41590-018-0274-0.
  • Wheaton, Joshua, and Maria Ciofani. “JunB controls intestinal effector programs in regulatory T cells,” 2019. https://doi.org/10.1101/772194.
  • Wheaton, Joshua D., Chen-Hao Yeh, and Maria Ciofani. “Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes.” J Immunol 199, no. 12 (December 15, 2017): 3931–36. https://doi.org/10.4049/jimmunol.1701134.
  • Carr, Tiffany M., Joshua D. Wheaton, Geoffrey M. Houtz, and Maria Ciofani. “JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation.” Nat Commun 8, no. 1 (August 21, 2017): 301. https://doi.org/10.1038/s41467-017-00380-3.
  • Glasmacher, Elke, Smita Agrawal, Abraham B. Chang, Theresa L. Murphy, Wenwen Zeng, Bryan Vander Lugt, Aly A. Khan, et al. “A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes.” Science 338, no. 6109 (November 16, 2012): 975–80. https://doi.org/10.1126/science.1228309.
  • Ciofani, Maria, Aviv Madar, Carolina Galan, Maclean Sellars, Kieran Mace, Florencia Pauli, Ashish Agarwal, et al. “A validated regulatory network for Th17 cell specification.” Cell 151, no. 2 (October 12, 2012): 289–303. https://doi.org/10.1016/j.cell.2012.09.016.
  • Huh, Jun R., Monica W. L. Leung, Pengxiang Huang, Daniel A. Ryan, Michael R. Krout, Raghu R. V. Malapaka, Jonathan Chow, et al. “Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.” Nature 472, no. 7344 (April 28, 2011): 486–90. https://doi.org/10.1038/nature09978.
  • Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “Determining γδ versus αß T cell development.” Nat Rev Immunol 10, no. 9 (September 2010): 657–63. https://doi.org/10.1038/nri2820.
  • Chong, Mark M. W., Natalie Simpson, Maria Ciofani, Grace Chen, Amélie Collins, and Dan R. Littman. “Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells.” Genes Dev 24, no. 7 (April 1, 2010): 659–69. https://doi.org/10.1101/gad.1901610.
  • Palomero, Teresa, Maria Luisa Sulis, Maria Cortina, Pedro J. Real, Kelly Barnes, Maria Ciofani, Esther Caparros, et al. “Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.” Nat Med 13, no. 10 (October 2007): 1203–10. https://doi.org/10.1038/nm1636.
  • Ciofani, Maria, Gisèle C. Knowles, David L. Wiest, Harald von Boehmer, and Juan Carlos Zúñiga-Pflücker. “Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation.” Immunity 25, no. 1 (July 2006): 105–16. https://doi.org/10.1016/j.immuni.2006.05.010.
  • Ciofani, Maria, and Juan Carlos Zúñiga-Pflücker. “Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism.” Nat Immunol 6, no. 9 (September 2005): 881–88. https://doi.org/10.1038/ni1234.
  • Ciofani, Maria, Thomas M. Schmitt, Amelia Ciofani, Alison M. Michie, Nicolas Cuburu, Anne Aublin, Janet L. Maryanski, and Juan Carlos Zúñiga-Pflücker. “Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation.” J Immunol 172, no. 9 (May 1, 2004): 5230–39. https://doi.org/10.4049/jimmunol.172.9.5230.