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Emily R. Miraldi, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-517-2063

Email emily.miraldi@cchmc.org

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Research Interests

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Systems biology; computational immunology; immuno-engineering; network inference

Biography

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Our research goal is immuno-engineering: to alter the behavior of specific immune cell populations in disease contexts (autoimmune disease, organ transplant, and cancer) without compromising the body’s homeostatic immune function (e.g. defense against pathogens). Thus, it is critical to develop a nuanced understanding of how different immune cells sense and respond to environmental cues across the body, in both physiological and disease settings. To this end, our lab’s major focus is reverse-engineering the underlying logic of immune cells (molecular networks that drive cellular responses) from high-dimensional molecular measurements of immune cells in action (sensing and responding to perturbations, disease conditions, etc.).

The lab’s focus is transcriptional regulatory network inference, modeling gene expression as a function of transcription factor activities, from gene expression and measurements of chromatin state. Chromatin accessibility measurements by ATAC-seq, together with transcription-factor DNA-binding preferences (motifs), can be used to broadly profile potential transcription factor binding events in relatively small populations of cells. Thus, we have used ATAC-seq with RNA-seq to enable de novo inference of transcriptional regulatory networks in physiological settings where sample material is limiting (e.g., intestinal immune cells in response to microbial/genetic perturbations). To date, most of these efforts have been in mouse models, as it is generally not possible to obtain sufficient sample material for similar experimental designs in human. To build human immune cell models, we are developing multi-task learning approaches to leverage evolutionarily conserved relationships and borrow statistical power from mouse datasets for inference in human. We are also developing methods to enable transcriptional regulatory network inference in very rare cell populations, as measured from single-cell RNA-seq experiments.

Learn more about the Miraldi Lab.

Education and Training

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BA: Oberlin College, Oberlin, OH.

PhD: Massachusetts Institute of Technology, Cambridge, MA.

Postdoctoral Fellow: New York University, New York School of Medicine, Flatiron Institute (Simons Foundation), New York, NY.

Publications

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View PubMed Publications

Karwacz K, Miraldi ER, Pokrovskii M, Madi A, Yosef N, Wortman I, Chen X, Watters A, Carriero N, Awasthi A, Regev A, Bonneau R, Littman DR, Kuchroo VK. Critical role of IRF1 and BATF in preparing the chromatin landscape during Tr1 differentiation. Nature Immunology. 2017.

Rocha PP, Raviram R, Fu Y, Kim J, Luo V, Aljoufi A, Swanzey E, Pasquarella A, Balestrini A, Miraldi ER, Bonneau R, Petrini J, Schotta G, Skok JA. A damage-independent role for 53BP1 that impacts break order and Igh architecture during class switch recombination. Cell Rep. 2016 Jun 28;16(1):48-55.

Raviram R, Rocha PD, Mueller CL, Miraldi ER, Fu Y, Swanzey E, Badri S, Proudhon C, Snetkova V, Bonneau R, Skok JA. 4C-ker: A method to reproducibly identify genome-wide interactions captured by 4C-Seq experiments. PLoS Comput Biol. 2016 Mar 3;12(3):e1004780.

Huang W, Thomas B, Flynn RA, Gavzy SJ, Wu L, Kim SV, Hall JA, Miraldi ER, Ng CP, Lee B, Rigo FW, Meadows S, Montoya NR, Herrera N, Domingos AI, Rastinejad F, Myers RM, Fuller-Pace FV, Bonneau R, Chang HY, Acuto O, Littman DR. DDX5 and its associated lncRNA Rmrp modulate Th17 cell effector functions. Nature. 2015 Dec 24;528(7583):517-22.

Sano T, Huang W, Hall JA, Chen A, Gravzy SJ, Lee J, Ziel J, Miraldi ER, Domingos AJ, Bonneau R, Littman DR. An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell. 2015;163(2):381-393.

Kurtz ZD, Mueller CL, Miraldi ER, Littman DR, Blaser MJ, Bonneau R. Sparse and compositionally robust inference of microbial ecological networks. PLoS Computational Biology. 2015;11(5):e1004226.

Yu B, Doraiswamy H, Chen X, Miraldi ER, Ortiz M, Hafemeister C, Bonneau R, Silva CT. Genotet: an interactive web-based visual exploration framework to support validation of gene regulatory networks. IEEE Trans Vis Comput Graph. 2014 Dec;20(12):1903-12.

Longman RS, Diehl GE, Victorio DA, Huh JH, Galan C, Miraldi ER, Swaminath A, Bonneau R, Scherl EJ, Littman DR. CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. Journal of Experimental Medicine. 2014;211(8):1571-1583.

Miraldi ER, Sharfi H, Friedline RH, Johnson H, Zhang T, Lau K, Ko HJ, Curran TG, Haigis KM, Yaffe YB, Bonneau R, Lauffenburger DA, Kahn BB, Kim J, Neel BG, Saghatelian A, White FM. Molecular network analysis of protein-tyrosine phosphorylation and altered lipid metabolism in liver-specific PTP1b deletion mice. Integrative Biology. 2013;5(7):940-963.

Huang PH, Miraldi ER, Xu AM, Kundukulam VA, Del Rosario AM, Flynn RA, Cavenee WK, Furnari FB, White FM. Phosphotyrosine signaling analysis of site-specific mutations on EGFRvIII identifies determinants governing glioblastoma cell growth. Molecular BioSystems. 2010;6(7):1227-37.

Miraldi ER, Thomas PJ, Romberg L. Allosteric models for cooperative polymerization of linear polymers. Biophysical Journal. 2008;95(5):2470-2486.

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Emily R. Miraldi, PhD

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