William E. Paul, M.D.
Chief, Laboratory of Immunology
Chief, Cytokine Biology Unit, LI
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 principal topics of the group are the study of the mechanisms of action and biologic functions of type I cytokines, principally IL-4 and IL-13; regulation of CD4+ T-cell differentiation, function, and plasticity; transcriptional networks underlying CD4 T-cell differentiation; strategies to enhance primary and secondary immune responses; new approaches to vaccine development; dynamics of naïve and memory lymphocyte populations during homeostatic conditions and in response to antigenic stimulation; and induction and maintenance of immunologic memory.

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

Transcriptional control of Th2 differentiation (Paul WE, Zhu J. How are TH2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10:225-35.)

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.
back to top
Biography
Chief of the Laboratory of Immunology (LI) since 1970, Dr. Paul served as director of the NIH Office of AIDS Research and as NIH Associate Director for AIDS Research from 1994 to 1997. He is the founding editor of the Annual Review of Immunology and is a member of the editorial boards of Immunity and the Proceedings of the National Academy of Sciences. He is a member of the National Academy of Sciences, its Institute of Medicine, and the Association of American Physicians. He also is a fellow of the American Academy of Arts and Sciences. He was president of the American Association of Immunologists and the American Society for Clinical Investigation. 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; and the Max Delbruck Medal. Dr. Paul is 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 is 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.
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
back to top
Selected Publications
Younes SA, Punkosdy G, Caucheteux S, Chen T, Grossman Z, Paul WE. Memory phenotype CD4 T cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells. PLoS Biol. 2011 Oct;9(10):e1001171.
O’Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science. 2010 Feb 26;327(5969):1098-102.
Guo L, Wei G, Zhu J, Liao W, Leonard WJ, Zhao K, Paul W. IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13463-8.
Ben-Sasson SZ, Hu-Li J, Quiel J, Cauchetaux S, Ratner M, Shapira I, Dinarello CA, Paul WE. IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7119-24.
Zhu J, Davidson TS, Wei G, Jankovic D, Cui K, Schones DE, Guo L, Zhao K, Shevach EM, Paul WE. Down-regulation of Gfi-1 expression by TGF-beta is important for differentiation of Th17 and CD103+ inducible regulatory T cells. J Exp Med. 2009 Feb 16;206(2):329-41.
Yamane H, Zhu J, Paul WE. Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment. J Exp Med. 2005 Sep 19;202(6):793-804.
For a complete listing, visit PubMed.
back to top