PEOPLE

Will Bailis, PhD

Assistant Professor of Microbiology
Perelman School of Medicine at the University of Pennsylvania
Assistant Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania

Contact InformationChildren's Hospital of Philadelphia
1211B Abramson Research Center
3615 Civic Center Blvd

Philadelphia, PA, 19104
Office: 215-590-9396

Email: bailisw@email.chop.edu

Specialty Division

Immunobiology and Experimental Pathology

Itmat Expertise

How metabolism regulates immune cell state by controlling cellular biochemical potential

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.

Education

B.A. (Biochemistry), Vassar College, Pouhkeepsie, NY, 2008
Ph.D. (Immunology), University of Pennsylvania, Philadelphia, PA, 2014

Specialty Certification

Postgraduate Training

Postdoctoral Fellow, Immunometabolism, Yale School of Medicine, New Haven, CT, 2014-2018

Awards and Honors

Oliver M. Lammert Prize, Vassar College, For Excellence In Biochemistry, 2008
Distinguished Honors, Vassar College, Poughkeepsie, NY, 2008
Cancer Research Institute Training Award, Cancer Research Institute, 2009
NIH Developmental Biology T32, University of Pennsylvania, Philadelphia, PA, 2010
Ruth L. Kirschstein National Research Service Award F31 – “The Requirement For TRIB2 in the Maintenance of Accute Myeloid Leukemia”, 2011
CRI Irvington Postdoctoral Fellowship – “Identification and Characterization of Immune Escape Mechanisms in Leukemia”, 2015
Yale Lung SPORE CDP/DRP Pilot Award – $50,000 to “Cas9 screen for identification of novel lung cancer co-therapies”
Peer, 2017

Memberships and Professional Organizations

Web Links


Selected Publications

Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection

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., Cell 178(5 ): 1176-1188, 2019, PMID:31442406

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Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function

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, Nature 571(7765): 403-407, 2019, PMID:31217581

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The translation of non-canonical open reading frames controls mucosal immunity

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, Nature 564(7736): 434-438, 2018, PMID:30542152

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Circuit Design Features of a Stable Two-Cell System

Zhou X, Franklin RA, Adler M, Jacox JB, Bailis W, Shyer JA, Flavell RA, Mayo A, Alon U, Medzhitov R, Cell 172(4): 744-757, 2018, PMID:29398113

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MAFB enhances oncogenic Notch signaling in T cell acute lymphoblastic leukemia

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, Science Signaling 10(505): , 2017, PMID:29138297

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No Oxygen? No Glucose? No Problem: Fatty Acid Catabolism Enhances Effector CD8+ TILs

Bailis W, Shyer J, Chiorazzi M, and Flavell RA., Cancer Cell 32(3): 280-81, 2017, PMID:28898693

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m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways

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., Nature 548(7667): 338-42, 2017, PMID:28792938

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Delta/Notch-Like EGF-Related Receptor (DNER) Is Not a Notch Ligand

Greene M, Lai Y, Pajcini K, Bailis W, Pear WS, Lancaster E., PLoS One 11(9): , 2016, PMID:27622512

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The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan

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., Nature 537(7619): 239-43, 2016, PMID:27525555

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Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

Nowarski R, Jackson R, Gagliani N, de Zoete MR, Palm NW, Bailis W, Low JS, Harman CC, Graham M, Elinav E, Flavell RA., Cell 163(6): 1444-56, 2015, PMID:26638073

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