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

All biological processes operate under biochemical constraints. The Bailis lab aims to understand how metabolism controls immune cell state by setting the biochemical potential of cells and tissues. We have set out to accomplish this by leveraging a CRISPR/Cas9 screening system compatible with gene editing in nearly every population of primary immune cells. This technology allows us to perform high-throughput reverse genetic screens, both in vitro and in in vivo adoptive transfer models, and interrogate metabolism at the network level to uncover the biochemical processes they regulate. Our work is currently focused in two main 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. We aim to elucidate how this biochemical partitioning is utilized by the immune system to regulate processes such cellular reprogramming during immune cell activation and how these cells sense and respond to alterations in tissue-level homeostasis.

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 metabolism influences post-translational modifications – the majority of which are derived from metabolites and/or generated by enzymes that use metabolites as cofactors – on signaling proteins (such as receptors and transcription factors) and histones.

Selected Publications

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.

Bailis W, Shyer J, Chiorazzi M, and Flavell RA.: No Oxygen? No Glucose? No Problem: Fatty Acid Catabolism Enhances Effector CD8+ TILs. Cancer Cell 32(3): 280-81, September 2017.

Li HB, Tong J, Zhu S, Batista PJ, Duffy EE, Zhao J, Bailis W, Cao G, Kroehling L, Chen Y, Wang G, Broughton JP, Chen YG, Kluger Y, Simon MD, Chang HY, Yin Z, Flavell RA.: m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature 548(7667): 338-42, August 2017.

Greene M, Lai Y, Pajcini K, Bailis W, Pear WS, Lancaster E.: Delta/Notch-Like EGF-Related Receptor (DNER) Is Not a Notch Ligand. PLoS One 11(9), September 2016 Notes: e0161157.

Kotzin JJ, Spencer SP, McCright SJ, Kumar DBU, Collet MA, Mowel WK, Elliott EN, Uyar A, Makiya MA, Dunagin MC, Harman CCD, Virtue AT, Zhu S, Bailis W, Stein J, Hughes C, Raj A, Wherry EJ, Goff LA, Klion AD, Rinn JL, Williams A, Flavell RA, Henao-Mejia J.: The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan. Nature 537(7619): 239-43, September 2016.

Nowarski R, Jackson R, Gagliani N, de Zoete MR, Palm NW, Bailis W, Low JS, Harman CC, Graham M, Elinav E, Flavell RA.: Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis. Cell 163(6): 1444-56, December 2015.

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Last updated: 09/03/2019
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