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.
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
- Deciphering the role of noncoding variation in the pathogenesis of multiple sclerosis
- Cell and Molecular Biology Training Program
- Genetic and Genomics Training Grant
- Basic Immunology Training Program
- Regulatory mechanisms governing Th17 cell effector identity and plasticity
- Molecular Mycology and Pathogenesis Training Program
- Transplant Infectious Diseases Interdisciplinary Research Training Grant (TIDIRTG)
- Structural Biological Development of Fungal-Specific Calcineurin Inhibitors
- Regulation of the type 1 program during ILC3 plasticity
- Regulatory Mechanisms of CD4+ T Cell Differentiation
- Organization and Function of Cellular Structure
- Network approach to dissecting genetic mediators of Multiple Sclerosis
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.” Nature Communications 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.
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.
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.