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William E. Paul, M.D.

Photo of William E. Paul, M.D.

Formerly Chief, Laboratory of Immunology

Formerly Chief, Cytokine Biology Unit

National Institutes of Health Distinguished Investigator

Major Areas of Research

  • Cytokines: characterization, regulation of production, mode of action, and mechanism of receptor function
  • Regulation of lymphocyte activation, differentiation, and proliferation
  • Lymphocyte dynamics in health and in chronic infection, including HIV
  • Immunologic memory and strategies for vaccine development

Program Description

The Cytokine Biology Unit studies the mechanisms of action and biologic functions of cytokines, emphasizing the role of the type II cytokines (IL-4, IL-13, and IL-5) as well as members of the IL-1 cytokine family. The unit also carries out research on the mechanisms through which naïve CD4 T cells differentiate into the various Th phenotypes, most notably into the molecular mechanisms underlying Th2 commitment. It has recently emphasized innate functions of lymphocytes, both those of conventional Th cells, most notably the capacity of Th2 cells to produce IL-13 and IL-5 in response to cytokine signals, and the consequent protective functions of these cells. An important research effort now centers on a newly described population of innate lymphoid cells, Kbri cells, that act as progenitors of ILC2 and ILC3 cells and respond to inflammatory/infectious stimulants. It has developed new strategies to enhance immune responses with the goal of increasing the protective capacity of weak vaccines.

illustration of comparative evolutionary trees of human and insect type I cytokines and cognate receptors
Comparative evolutionary trees of human and insect type I cytokines and cognate receptors (Boulay JL, O'Shea JJ, Paul WE. Molecular phylogeny within type I cytokines and their cognate receptors. Immunity. 2003;19:159-63.) View Larger Image
illustration of Th2 cells
Naïve CD4 T cells differentiation to Th2 cells is controlled by signal strength with low intensity signals favoring Th2 differentiation and high intensity signals suppressing Th2 differentiation.
Credit: Debbie Maizels
Flexibility and plasticity among CD4 Th cells
Flexibility and plasticity among CD4 Th cells. The classical view that naïve CD4 T cells differentiate into cells of distinct lineage that are largely not interconvertible has been challenged by recent results showing that these cells can adopt new phenotypes. The degree and physiologic significance of such plasticity remain to be determined. From O’Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science. 2010 Feb 26;327(5969):1098-102.

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A member of the Laboratory of Immunology (LI) beginning in 1968 and then Chief of the LI from 1970 to 2015, Dr. Paul also served as director of the National Institutes of Health (NIH) Office of AIDS Research and as NIH Associate Director for AIDS Research from 1994 to 1997. He was the editor of the Annual Review of Immunology for volumes 1 through 30 and a member of the editorial boards of Immunity and the Proceedings of the National Academy of Sciences among many others. He was elected a member of the National Academy of Sciences, its Institute of Medicine, and the Association of American Physicians and a fellow of the American Academy of Arts and Sciences. He served as president of the American Association of Immunologists and the American Society for Clinical Investigation, as well as a member of numerous advisory boards in the United States and internationally. His honors include the Founders Prize, Texas Instruments Foundation; Life Sciences Award, Federation of American Societies for Experimental Biology; Abbott Laboratories Award in Clinical and Diagnostic Immunology; the Max Delbruck Medal; and the Clemens von Pirquet Medal. He received the Lifetime Achievement Award and the Excellence in Mentoring Award from the American Association of Immunologists and the Honorary Lifetime Membership Award from the International Cytokine Society. Dr. Paul was the recipient of honorary degrees from the State University of New York, the Hebrew University of Jerusalem, the University of Rome La Sapienza, and the National University of Athens, among others. He also served as an adjunct professor at the University of Pennsylvania School of Medicine and a Raymond and Beverly Sackler Senior Professor by Special Appointment at Tel Aviv University.

Sadly, Dr. Paul passed away September 18, 2015. He will be missed and remembered annually by an NIH Wednesday afternoon lecture named in his honor. The first one is planned for November 7, 2016, along with a one-day special symposium. To learn more about his life, please read the following:

Paul WE. Endless Fascination. Annu Rev Immunol. 2014;32:1-24.

William E. Paul (1936-2015). Nature. 2015;526:324.

William Erwin Paul (1936-2015). Cell. 2015;163:529-30.

William E. Paul, M.D. (1936–2015). Immunity. 2015;43:617-9.

Bill Paul: The heart of immunology. Proc Natl Acad Sci U S A. 2015;112:14117-8.

William E. Paul 1936-2015. Nat Immunol. 2015;16:1205.


Research Group

Photo of research group
​Pictured, L-R: Tao Chen, Jinfang Zhu, Liying Guo, Xi Chen, Ryoji Yagi, William Paul, Ilkka Junttila, Jane Hu-Li, Stephane Caucheteux, Michelle Crank, Suveena Sharma, and Zami Ben-Sasson. Not depicted: Hidehiro Yamane and Zvi Grossman

Liying Guo, Ph.D, Staff Scientist
Stephane Cauchetaux, Ph.D. Postdoctoral Fellow
Juan Quiel, Ph.D. Postdoctoral Fellow
Hidehiro Yamane, Ph.D., Postdoctoral Fellow
Michelle Crank, M.D., Clinical Fellow
S.Z. Ben-Sasson, Ph.D., Adjunct Investigator
Zvi Grossman, Ph.D., Adjunct Investigator
Xi Chen, M.D., Senior Laboratory Technician
Jane Hu-Li, B.Sc., Senior Laboratory Technician

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Selected Publications

Guo L, Huang Y, Chen X, Hu-Li J, Urban JF Jr, Paul WE. Innate immunological function of TH2 cells in vivo. Nat Immunol. 2015;16:1051-9.

Huang Y, Guo L, Qiu J, Chen X, Hu-Li J, Siebenlist U, Williamson PR, Urban JF Jr, Paul WE. IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells. Nat Immunol. 2015;16:161-9.

Paul WE, Milner JD, Grossman Z. Pathogen-sensing, regulatory T cells, and responsiveness-tuning collectively regulate foreign- and self-antigen mediated T-cell responses. Cold Spring Harb Symp Quant Biol. 2013;78:265-76.

Guo L, Martens C, Bruno D, Porcella SF, Yamane H, Caucheteux SM, Zhu J, Paul WE. Lipid phosphatases identified by screening a mouse phosphatase shRNA library regulate T-cell differentiation and protein kinase B AKT signaling. Proc Natl Acad Sci U S A. 2013;110:E1849-56.

Ben-Sasson SZ, Hogg A, Hu-Li J, Wingfield P, Chen X, Crank M, Caucheteux S, Ratner-Hurevich M, Berzofsky JA, Nir-Paz R, Paul WE. IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells. J Exp Med. 2013;210:491-502.

Zhu J, Jankovic D, Oler AJ, Wei G, Sharma S, Hu G, Guo L, Yagi R, Yamane H, Punkosdy G, Feigenbaum L, Zhao K, Paul WE. The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses. Immunity. 2012;37:660-73.

Paul WE. Bridging innate and adaptive immunity. Cell. 2011;147:1212-5.

For a complete listing, visit PubMed.

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Last Updated February 23, 2016