PEOPLE

Will Bailis, PhD

Assistant Professor of Microbiology
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

The Bailis lab aims to understand how human health is impacted by organismal and immune cell metabolism. We do so by leveraging in vitro and in vivo CRISPR/Cas9 screening systems compatible with gene editing in 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 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.

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, 2011
CRI Irvington Postdoctoral Fellowship, 2015
Yale Lung SPORE CDP/DRP Award, 2017
NIH NIAID Career Transition Award (K22), 2018
Paul Allen Frontiers Group Distinguished Investigator Award, 2020
NIH NIGMS Maximizing Investigators’ Research Award (R35), 2020

Memberships and Professional Organizations

Society for Leukocyte Biology, 2019 - Present
American Association of Immunologists, 2020 - Present

Web Links


Selected Publications

Skin-resident innate lymphoid cells converge on a pathogenic effector state

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, Nature, 2021

An in-vivo screen of noncoding loci reveals that Daedalus is a gatekeeper of a novel Ikaros-dependent checkpoint during haematopoiesis

*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, PNAS 118(3): , 2021, PMID:33446502

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Metabolic signaling in T cells

Justin A Shyer, Richard A Flavell, Will Bailis, Cell Research 30(8): 649-659, 2020, PMID:32709897

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The induction and function of the anti-inflammatory fate of TH17 cells.

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, Nature Communications 11(1): , 2020, PMID:32620760

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CRISPR/Cas9 Gene Targeting in Primary Mouse Bone Marrow-Derived Macrophages

Will Bailis, Methods in Molecular Biology 2097(): 223-230, 2020, PMID:31776929

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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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