Will Bailis, Ph.D.

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Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
1211B Abramson Research Center
3615 Civic Center Blvd
Philadelphia, PA 19104
Office: 215-590-9396
Education:
B.A. (Biochemistry)
Vassar College, Pouhkeepsie, NY, 2008.
Ph.D. (Immunology)
University of Pennsylvania, Philadelphia, PA, 2014.
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Description of Research Expertise

The Bailis lab aims aims to understand how metabolism underlies immunology and disease, by controlling the biochemistry of cells and tissues. We do so so using in vitro and in vivo CRISPR engineering of primary human and mouse immune cells. Together with next generation sequencing and metabolomics, this permits us to fully interrogate how metabolic networks control immune cell function. Our long term goal is to use this to develop novel diet and metabolite based therapies.


Our work is currently focused in three major areas:

1) How does spatial compartmentalization of metabolism regulate immune cell state?

Multicellular eukaryotes compartmentalize metabolic information at multiple levels. Within cells, biochemical reactions are separated by the organelles within which they occur; within tissues, metabolites can be divided between the cells that compose them; within an animal; different organ systems generate and consume distinct metabolic products that are shared throughout their host. Taking advantage of organelle tagging technologies that allow us to purify immune cell nuclei, ribosomes, and mitochondria from heterogeneous tissues, we aim to elucidate how this biochemical partitioning influences cell programming, tissue patterning, and disease outcome.

2) How does biochemical state control immune cell signaling potential?

In the context of immune cell activation, cellular metabolism is often understood to be one of many biological processes regulated downstream of classic signal transduction. From this top-down view, metabolism is a passive participant in cell reprogramming, acted upon by signaling pathways. There is now a large body of literature illustrating that metabolism can also act in a bottom-up fashion to regulate both signaling effectors as well as epigenetic modifications on the histones that control gene expression. In this manner, the biochemical potential of a cell has the capacity to tune both the quality and quantity of signaling that occurs as well as how that signal is received at target genes in the nucleus. We are actively investigating how signaling relays information through metabolism and how metabolism in turn influences the activity of signaling proteins.

3) How do inborn errors of metabolism impact the immune system?

Inborn errors of metabolism (IEM) are a group of rare genetic disorders that prevent the body from metabolizing food or removing nutrient waste. These defects result in a failure to produce certain essential nutrients or a toxic buildup of metabolites that can cause developmental delays, organ failure, and wasting. While IEM are traditionally not thought of as immunodeficiencies, many individuals with IEM display hallmarks of immune dysfunction, including recurrent and longer lasting infections. Working at Children’s Hospital of Philadelphia, we have the privilege to collaborate with physicians who work with these patients and their families. The goal of our work is to better understand how IEM alter immune cell function, in hopes of improving the care of patients with IEM and learning more broadly how the immune system can be modulated by metabolism. We do so by: 1) working directly with immune cells from IEM patients; 2) modeling the mutations found in these patients using CRISPR/Cas9 engineering of primary human immune cells; 3) performing in vivo infection and vaccination studies with genetic mouse models of these diseases.

Selected Publications

Bielecki P, Riesenfeld SJ, Hütter JC, Torlai Triglia E, Kowalczyk MS, Ricardo-Gonzalez RR, Lian M, Amezcua Vesely MC, Kroehling L, Xu H, Slyper M, Muus C, Ludwig LS, Christian E, Tao L, Kedaigle AJ, Steach HR, York AG, Skadow MH, Yaghoubi P, Dionne D, Jarret A, McGee HM, Porter CBM, Licona-Limón P, Bailis W, Jackson R, Gagliani N, Gasteiger G, Locksley RM, Regev A, Flavell RA: Skin-resident innate lymphoid cells converge on a pathogenic effector state. Nature February 2021.

*Harman CCD, *Bailis W (*Equal contribution), Zhao J, Hill L, Qu R, Jackson RP, Shyer JA, Steach HR, Kluger Y, Goff LA, Rinn JL, Williams A, Henao-Mejia J, Flavell RA : An in-vivo screen of noncoding loci reveals that Daedalus is a gatekeeper of a novel Ikaros-dependent checkpoint during haematopoiesis. PNAS 118(3), January 2021.

Justin A Shyer, Richard A Flavell, Will Bailis: Metabolic signaling in T cells. Cell Research 30(8): 649-659, August 2020.

Hao Xu, Theodora Agalioti, Jun Zhao, Babett Steglich, Ramez Wahib, Maria Carolina Amezcua Vesely, Piotr Bielecki, Will Bailis, Ruaidhri Jackson, Daniel Perez, Jakob Izbicki, Paula Licona-Limón, Vesa Kaartinen, Jens Geginat, Enric Esplugues, Eva Tolosa, Samuel Huber, Richard A Flavell, Nicola Gagliani: The induction and function of the anti-inflammatory fate of TH17 cells. Nature Communications 11(1), July 2020.

Will Bailis: CRISPR/Cas9 Gene Targeting in Primary Mouse Bone Marrow-Derived Macrophages. Methods in Molecular Biology. Katz S., Rabinovich P. (eds.). Humana, 2097: 223-230, 2020.

Amezcua Vesely MC, Pallis P, Bielecki P, Low JS, Zhao J, Harman CCD, Kroehling L, Jackson R, Bailis W, Licona-Limón P, Xu H, Iijima N, Pillai PS, Kaplan DH, Weaver CT, Kluger Y, Kowalczyk MS, Iwasaki A, Pereira JP, Esplugues E, Gagliani N, Flavell RA.: Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection. Cell 178(5 ): 1176-1188, August 2019.

Bailis W, Shyer J, Zhao J, Garcia Canaveras JC, Al Khaal FJ, Qu R, Steach HR, Bielecki P, Kahn O, Jackson R, Kluger Y, Maher 3rd LJ, Rabinowitz J, Craft J, and Flavell RA: Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function. Nature 571(7765): 403-407, July 2019.

Jackson R, Kroehling L, Khitun A, Bailis W, Jarret A, York AG, Khan OM, Brewer JR, Skadow MH, Duizer C, Harman CCD, Chang L, Bielecki P, Solis AG, Steach HR, Slavoff S, Flavell RA: The translation of non-canonical open reading frames controls mucosal immunity. Nature 564(7736): 434-438, December 2018 Notes: doi: 10.1038/s41586-018-0794-7.

Zhou X, Franklin RA, Adler M, Jacox JB, Bailis W, Shyer JA, Flavell RA, Mayo A, Alon U, Medzhitov R: Circuit Design Features of a Stable Two-Cell System. Cell 172(4): 744-757, February 2018 Notes: DOI: 10.1016/j.cell.2018.01.015.

Pajcini KP, Xu L, Shao L, Petrovic J, Palasiewicz K, Ohtani Y, Bailis W, Lee C, Wertheim GB, Mani R, Musuthamy N, Li Y, Meijerink JPP, Blacklow SC, Faryabi RB, Cherry S, Pear WS: MAFB enhances oncogenic Notch signaling in T cell acute lymphoblastic leukemia. Science Signaling 10(505), November 2017 Notes: doi: 10.1126/scisignal.aam6846.

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Last updated: 08/02/2021
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