Miraldi, ER, Pokrovskii, M, Waters, A, Castro, DM, De Veaux, N, Hall, J, Lee, J-Y, Ciofani, M, Madar, A, Carriero, N, Littman, D, and Bonneau, R. "Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells." Genome Research (January 29, 2019).
Maria Ciofani, PhD
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.
Education and Training
- Ph.D., University of Toronto (Canada), 2007
Selected Grants and Awards
- Transplant Infectious Diseases Interdisciplinary Research Training Grant
- Regulatory Mechanisms of CD4+ T Cell Differentiation
- The role of AP-1 family transcription factor networks in regulating Th17 cell effector identity
- Molecular Mycology and Pathogenesis Training Program
- Basic Immunology Training Program
- Network approach to dissecting genetic mediators of Multiple Sclerosis
Zuberbuehler, MK, Parker, ME, Wheaton, JD, Espinosa, JR, Salzler, HR, Park, E, and Ciofani, M. "The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells." Nature Immunology 20, no. 1 (January 2019): 73-85.
Wheaton, JD, Yeh, C-H, and Ciofani, M. "Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes." Journal of Immunology (Baltimore, Md. : 1950) 199, no. 12 (December 2017): 3931-3936.
Carr, TM, Wheaton, JD, Houtz, GM, and Ciofani, M. "JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation." Nature Communications 8, no. 1 (August 21, 2017): 301-null.
Bao, K, Carr, T, Wu, J, Barclay, W, Jin, J, Ciofani, M, and Reinhardt, RL. "BATF Modulates the Th2 Locus Control Region and Regulates CD4+ T Cell Fate during Antihelminth Immunity." Journal of Immunology (Baltimore, Md. : 1950) 197, no. 11 (December 2016): 4371-4381.
Glasmacher, E, Agrawal, S, Chang, AB, Murphy, TL, Zeng, W, Vander Lugt, B, Khan, AA, Ciofani, M, Spooner, CJ, Rutz, S, Hackney, J, Nurieva, R, Escalante, CR, Ouyang, W, Littman, DR, Murphy, KM, and Singh, H. "A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes." Science 338, no. 6109 (November 16, 2012): 975-980.
Ciofani, M, Madar, A, Galan, C, Sellars, M, Mace, K, Pauli, F, Agarwal, A, Huang, W, Parkhurst, CN, Muratet, M, Newberry, KM, Meadows, S, Greenfield, A, Yang, Y, Jain, P, Kirigin, FK, Birchmeier, C, Wagner, EF, Murphy, KM, Myers, RM, Bonneau, R, and Littman, DR. "A validated regulatory network for Th17 cell specification." Cell 151, no. 2 (October 12, 2012): 289-303.
Huh, JR, Leung, MWL, Huang, P, Ryan, DA, Krout, MR, Malapaka, RRV, Chow, J, Manel, N, Ciofani, M, Kim, SV, Cuesta, A, Santori, FR, Lafaille, JJ, Xu, HE, Gin, DY, Rastinejad, F, and Littman, DR. "Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity." Nature 472, no. 7344 (April 28, 2011): 486-490.
Ciofani, M, and Zúñiga-Pflücker, JC. "Determining γδ versus αß T cell development." Nat Rev Immunol 10, no. 9 (September 2010): 657-663. (Review)
Chong, MMW, Simpson, N, Ciofani, M, Chen, G, Collins, A, and Littman, DR. "Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells." Genes Dev 24, no. 7 (April 1, 2010): 659-669.
Palomero, T, Sulis, ML, Cortina, M, Real, PJ, Barnes, K, Ciofani, M, Caparros, E, Buteau, J, Brown, K, Perkins, SL, Bhagat, G, Agarwal, AM, Basso, G, Castillo, M, Nagase, S, Cordon-Cardo, C, Parsons, R, Zúñiga-Pflücker, JC, Dominguez, M, and Ferrando, AA. "Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia." Nat Med 13, no. 10 (October 2007): 1203-1210.
Ciofani, M, Knowles, GC, Wiest, DL, von Boehmer, H, and Zúñiga-Pflücker, JC. "Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation." Immunity 25, no. 1 (July 2006): 105-116.
CIOFANI, M. "Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism." Nat Immunol. 6, no. 9 (2005): 881-888.
Ciofani, M, Schmitt, TM, Ciofani, A, Michie, AM, Cuburu, N, Aublin, A, Maryanski, JL, and Zúñiga-Pflücker, JC. "Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation." J Immunol 172, no. 9 (May 1, 2004): 5230-5239.